The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index; 11 of the 24 sources its claims cite were checked for support.
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Open accessAbstract
BACKGROUND: The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS: In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS: A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS: In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).
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Claims the paper makes
41 Own result · 14 Own method · 5 Own interpretation · 4 Partly supported · 4 No full text of the sources · 3 Supported · 1 Supported so far · 1 Sources not found · 1 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial,14 the GLP-1–receptor agonist lixisenatide, which is shorter-acting than and structurally dissimilar to liraglutide, did not show any cardiovascular benefit in patients with diabetes and a recent acute coronary syndrome.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Supportedcites [14] source
The Study Design section identifies ELIXA as a trial in patients with type 2 diabetes and a recent acute coronary syndrome. The Results report no superiority of lixisenatide over placebo for the primary cardiovascular end point, and the Discussion describes its cardiovascular effect as neutral. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The pattern of cardiovascular benefits that were associated with liraglutide in our trial appears to differ from that with the sodium–glucose cotransporter 2 inhibitor empagliflozin in the previously reported EMPA-REG OUTCOME trial.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Supportedcites [12] source
The source is the EMPA-REG OUTCOME trial and establishes the empagliflozin side of the comparison. Its Cardiovascular Outcomes section (p. 4) reports lower cardiovascular death and heart-failure hospitalization, but no significant difference in myocardial infarction or stroke. The comparison with liraglutide is the citing authors’ interpretation, not a finding attributed to this trial. (LLM, conf=0.92)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The time to benefit emerged earlier in that trial than in the present trial”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The discussion on p. 9 says that reductions in cardiovascular and all-cause death occurred early in EMPA-REG OUTCOME and continued throughout the study. It does not compare the time to benefit with that of the citing authors’ present trial, so the ‘earlier than’ comparison is not supported by this source alone. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“It has been associated with an increase in pulse rate.7,8”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [7] source
- Supportedcites [8] Robinson LE, 2013, BMJ Open source
The Results (Heart rate) report that liraglutide increased heart rate compared with both placebo and active control. This directly supports the cited statement that liraglutide has been associated with an increased pulse rate. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the diastolic blood pressure was 0.6 mm Hg (95% CI, 0.2 to 1.0) higher in the liraglutide group”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > CARDIOVASCULAR RISK FACTORS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Medullary thyroid carcinoma occurred in no patient in the liraglutide group and in 1 in the placebo group.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The incidence of a composite outcome of renal or retinal microvascular events was lower in the liraglutide group than in the placebo group (hazard ratio, 0.84; 95% CI, 0.73 to 0.97; P = 0.02)”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > MICROVASCULAR OUTCOMES
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean levels of serum amylase and lipase were higher in the liraglutide group than in the placebo group”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the heart rate was 3.0 beats per minute (95% CI, 2.5 to 3.4) higher in the liraglutide group”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > CARDIOVASCULAR RISK FACTORS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the systolic blood pressure was 1.2 mm Hg (95% CI, 1.9 to 0.5) lower in the liraglutide group”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > CARDIOVASCULAR RISK FACTORS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 21
- Probably not a substantial claim. 17
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There are a number of other trials regarding cardiovascular outcomes in high-risk cohorts of patients with type 2 diabetes in which similar magnitude effects on glycemic control have been shown but without significant benefits with respect to rates of cardiovascular events or death.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [15] source
- Supportedcites [16] source
The insulin-use and achieved fasting-glucose section reports a modest between-group glycemic difference, and the Discussion reports no reduction in cardiovascular outcomes. The Discussion’s outcome figure also shows no significant difference in all-cause mortality (hazard ratio 0.98; P=0.70). ORIGIN included people with early type 2 diabetes as well as people with impaired fasting glucose or glucose tolerance; the citation supports this trial as an example, not the plurality of trials on its own. (LLM, conf=0.88)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The Results (p. 1) report a small improvement in glycated hemoglobin with sitagliptin and no reduction in the primary cardiovascular outcome; Other Secondary Outcomes (p. 4) report no significant difference in deaths. The Discussion (p. 8) also says two other DPP-4 inhibitor trials found no reduction in major adverse cardiovascular events. It does not establish that those other trials had similar-magnitude glycemic effects or no mortality benefit. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [18] source
- Supportedcites [19] source
The Discussion reports that saxagliptin significantly improved glycemic control in patients at high cardiovascular risk but provided no cardioprotective benefit. Table 2 shows no significant reduction in the primary cardiovascular endpoint or death from any cause, making this trial an example of the pattern described. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [20] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“the heterogeneity of the direction and magnitude of the effects on the components of the primary composite outcome in that trial contrasts with the consistency of the effect in the present trial.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Supportedcites [12] source
Cardiovascular Outcomes (p. 4) reports a substantially lower risk of cardiovascular death with empagliflozin, a slightly lower rate of myocardial infarction, and a slightly higher rate of stroke; the latter two differences were not significant. These findings support the citing paper’s characterization of heterogeneous directions and magnitudes among the primary composite’s components. The comparison with the present trial is the citing authors’ own framing. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There were more episodes of gallstone disease with liraglutide, a finding that has been reported previously.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Partly supportedcites [26] sourceExperimental — accuracy not yet measured
The Safety section reports more gallbladder-related adverse events with liraglutide than placebo (1.2% and 1.9% versus 0.5%). It does not identify those events specifically as gallstone disease or say that this particular finding had been reported previously. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Its efficacy in lowering glucose levels has been established, and it has been associated with slight reductions in weight and blood pressure.6–8”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > CONCLUSIONS
What the sources say
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
The GLP-1RAs Glycaemic Efficacy section reports that liraglutide lowers fasting and postprandial glucose and HbA1c. The Non-glycaemic Effects section reports weight reductions with liraglutide, but it does not establish a blood-pressure reduction for liraglutide; it says a 52-week trial extension found no significant improvement in systolic blood pressure. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [7] source
- Partly supportedcites [8] Robinson LE, 2013, BMJ Open sourceExperimental — accuracy not yet measured
The Key messages and Results (Body weight; Blood pressure) support modest reductions in weight and systolic blood pressure with liraglutide and exenatide. The paper does not assess glucose-lowering efficacy; that part appears in titles in its References, but is not established by this analysis. Diastolic blood-pressure reductions were not statistically significant. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Acute gallstone disease was more common with liraglutide than with placebo (in 145 vs. 90 patients), including severe events (in 40 vs. 31).”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plaincorrelationaln = 90- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority).”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > RESULTS
plainn = 4,668- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and also fewer patients with leukemia (5 vs. 14)”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The overall rates of benign or malignant neoplasms were higher in the liraglutide group than in the placebo group, but the difference was not significant”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a difference that was driven by a lower rate of nephropathy events in the liraglutide group (1.5 vs. 1.9 events per 100 patient-years of observation; hazard ratio, 0.78; 95% CI, 0.67 to 0.92; P = 0.003)”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > MICROVASCULAR OUTCOMES
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 13 patients with pancreatic cancer in the liraglutide group and 5 in the placebo group.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plainn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Our trial had greater statistical power and included patients with a higher baseline glycated hemoglobin level than did most previous studies.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007).”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > RESULTS
plainn = 219- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were fewer patients with prostate cancer in the liraglutide group than in the placebo group (26 vs. 47)”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The frequencies of nonfatal myocardial infarction and nonfatal stroke were lower in the liraglutide group than in the placebo group, although the differences were not significant”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > CARDIOVASCULAR OUTCOMES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present trial, there were fewer hospitalizations for heart failure among patients in the liraglutide group than among those in the placebo group, although the difference was not significant.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Calcitonin levels over time were similar in the two groups (data not shown).”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > SAFETY AND ADVERSE EVENTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The frequencies of nonfatal myocardial infarction and nonfatal stroke were lower in the liraglutide group than in the placebo group, although the differences were not significant”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > CARDIOVASCULAR OUTCOMES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P =0.02).”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > RESULTS
plainn = 381 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Higher levels of lipase and amylase were observed in the liraglutide group, a finding that is similar to results in other studies.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [24] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, no obvious single explanation in terms of either the study designs or the included populations is apparent to explain the divergent findings across this body of medical literature.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The vital status was known in 99.7% of the patients. A total of 96.8% of the patients completed a final visit, died, or had a primary outcome.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > OVERVIEW OF TRIAL CONDUCT
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean percentage of time that patients received the trial regimen was 84% for liraglutide and 83% for placebo.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > RESULTS > OVERVIEW OF TRIAL CONDUCT
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An independent data and safety monitoring committee performed ongoing safety surveillance and had access to all the data in an unblinded fashion.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > METHODS > TRIAL DESIGN AND OVERSIGHT
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Randomized trials of this type, despite their size, are not powered to determine the effect of drugs on cancer risk and can therefore neither confirm nor exclude such a possibility.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Consequently, regulatory authorities have mandated cardiovascular safety assessments of new diabetes treatments.4,5”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > CONCLUSIONS
What the sources say
- Not matchedcites [4] Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus. London: European Medicines Agency, 2012.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [5] Guidance for industry: diabetes mellitus — evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. Silver Spring, MD: Department of Health and Human Services, 2008.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All the patients who underwent randomization were included in the primary and exploratory analyses”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > METHODS > STATISTICAL ANALYSIS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Randomization was stratified according to the estimated glomerular filtration rate (eGFR) at screening”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > METHODS > PROCEDURES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Assuming a withdrawal rate of less than 10%, a minimum exposure to the trial regimen of 42 months, a null hypothesis hazard ratio of 1.30 or more, 90% power, and a one-sided alpha level of 0.025, we calculated that 8754 patients would need to undergo randomization if we were to observe at least 611 primary outcomes.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > METHODS > STATISTICAL ANALYSIS
plainn = 8,754- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Furthermore, concern has been raised about the cardiovascular safety of antihyperglycemic therapies.3”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > Abstract > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [3] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“all of which were adjudicated in a blinded fashion by an external, independent event-adjudication committee.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > METHODS > OUTCOMES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, no adjustments were made for multiplicity of exploratory outcomes.”
§ Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The macrovascular benefits of glycemic control are less certain than its microvascular benefits.
“Although glycemic control is associated with reductions in the risk of microvascular complications, the macrovascular benefits of glycemic control are less certain.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“and semaglutide reduced the risk of new or worsening nephropathy (a composite of persistent UACR >300 mg/g creatinine, doubling of serum creatinine, or ESKD) by 36% (each P < 0.01).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“dulaglutide reduced the composite kidney outcome (risk of ≥40% sustained decline in eGFR, kidney failure, or kidney-related death) by 25%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [104]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“canagliflozin reduced the risk of progression of albuminuria by 27% and the risk of reduction in eGFR, kidney failure, or death from kidney failure by 40%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [104]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Therapies shown to positively affect albuminuria and declining eGFR include ACE inhibitors, ARBs, SGLT2is, GLP-1 RAs, and the nonsteroidal mineralocorticoid antagonist finerenone.197,209,239,242,393,423–435”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [423]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GLP‐1 receptor agonists (GLP‐1RAs) improve glycemic control, promote weight loss and reduce major adverse cardiovascular events in high‐risk patients with T2DM [1, 2, 3]”
From Effects of GLP ‐1 Receptor Agonists and Dual GIP / GLP ‐1 Receptor Agonists on Inflammatory and Metabolic Biomarkers in Type 2 Diabetes: A Systematic Review and Meta‐Analysis (2026) · cites this paper as [2]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GLP-1RAs confer substantial benefits for individuals with AS owing to their multifaceted impact on various aspects of cardiovascular health.39,40,446”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [446]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It was then found that patients with diabetes and high cardiovascular risk that were treated with liraglutide and semaglutide, but not exenatide, had a lower risk of non-fatal myocardial infarction and stroke [66, 70, 71] and another GLP-1R agonist, dulaglutide, reduced major adverse cardiovascular events [72].”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [70]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Prior studies have reported substantial benefits of GLP-1 agonists in reducing cardiovascular disease (CVD) risk and promoting weight loss.1,2”
From GLP-1 receptor agonist discontinuation among patients with obesity and/or type 2 diabetes (2024) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The longest controlled trials of GLP-1 receptor agonist usage are 3–4 years,12,13 and the long-term effects beyond this time are not well-described.”
From Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications improve health outcomes in patients with type 2 diabetes mellitus (T2DM).”
From Differences in GLP-1 RA medication adherence across place-based variables in patients with diabetes living in Wisconsin (2025) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent randomized clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in at-risk individuals with type 2 diabetes.”
From Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review (2020) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“as initially evidenced by the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, which reported acute gallstone disease rates of 3.1% in the liraglutide group versus 1.9% in the placebo cohort (P<0.001) [33].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [33]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Proven safe and effective in older adults with diabetes and obesity, with robust CVOT support [34].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [34]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Long-term trials like LEADER confirmed cardiovascular and renal safety for liraglutide in T2D, with no increased risk of pancreatitis or thyroid malignancy [34].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [34]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GLP-1 agents, including dipeptidyl peptidase-4 (DPP-4) inhibitor and glucagon-like peptide-1 receptor agonist (GLP-1 Ra), enhance insulin secretion in pancreatic b-cell and showed many benefits in treating diabetes mellitus type 2 but are not a common choice for GDM [117,118].”
From Gestational Diabetes Mellitus—Recent Literature Review (2022) · cites this paper as [118]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“liraglutide reduced the risk of new or worsening nephropathy (a composite of persistent macroalbuminuria, doubling of serum creatinine, ESKD, or death from ESKD) by 22%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the evidence supporting the cardiovascular benefits of GLP-1RAs is more compelling, 95 likely because of the higher pharmacological GLP-1 levels achieved by GLP-1RAs compared to the physiological levels with DPP-4 inhibitors.127”
From The effect of GLP ‐1 receptor agonists on circulating inflammatory markers in type 2 diabetes patients: A systematic review and meta‐analysis (2025) · cites this paper as [95]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“No increased risk of heart failure hospitalization has been identified in the cardiovascular outcomes trials of the GLP-1 RAs lixisenatide, liraglutide, semaglutide, exenatide once weekly, albiglutide, or dulaglutide compared with placebo (261,264,265,296,297).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [261]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Large clinical trials have shown benefits of newer glucose-lowering medications on cardiovascular and kidney outcomes in patients with CKD with type 2 diabetes.5, 6, 7, 8, 9, 10, 11, 12, 13, 14”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Large clinical trials have shown benefits of newer glucose-lowering medications on cardiovascular and kidney outcomes in patients with CKD with type 2 diabetes.5, 6, 7, 8, 9, 10, 11, 12, 13, 14”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Five large randomized clinical trials (the EMPA-REG OUTCOME, the Canagliflozin Cardiovascular Assessment Study [CANVAS], the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 [DECLARE–TIMI 58], CREDENCE, and DAPA-CKD) demonstrated cardiovascular benefits, and kidney protective benefits of SGLT2i.5, 6, 7, 8,11,12,34”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, significant benefits of SGLT2i were shown among the subgroup patients (aged greater than or equal to 65 years) in the study of EMPAREG, CANVAS, DECLARE, and DAPA-CKD.6, 7, 8,11,12,34”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [11]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Major cardiovascular trials in patients with T2DM, including the LEADER, SUSTAIN-6, HARMONY Outcomes and REWIND trials, 22 -25 have collectively demonstrated a significant reduction in cardiovascular death with GLP-1RA therapy, ranging from 12% to 26%.”
From Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials (2021) · cites this paper as [22]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Large cardiovascular outcome trials have shown that GLP‐1RAs reduce major adverse cardiovascular events and slow progression of kidney disease in high‐risk patients [1, 2, 3].”
The cited source says what the claim attributes to it.
In the citing paper
“Initially approved for T2D management, GLP-1 RAs have also demonstrated cardiovascular and renal benefits [5–7].”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Similarly, the LEADER trial with liraglutide showed a numerically higher, though non-significant, rate of diabetic retinopathy events compared to placebo (HR, 1.15; 95% CI, 0.87 to 1.52) [33].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [33]
The cited source says what the claim attributes to it.
In the citing paper
“the LEADER trial comparing liraglutide and placebo in patients with T2D (18 cases in 4668 participants randomized to liraglutide treatment vs. 23 in 4672 with placebo treatment) (67).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [67]
The cited source says what the claim attributes to it.
In the citing paper
“At 1.8 mg, it reduced MACE by 13% (primary outcome) and CV mortality by 22% in LEADER [34].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [34]
The cited source says what the claim attributes to it.
In the citing paper
“in the LEADER trial, a non-significant trend towards DRP was observed for liraglutide”
From Safety of Semaglutide (2021) · cites this paper as [121]
The cited source says what the claim attributes to it.
In the citing paper
“patients on liraglutide lost 2.3 kg more and were less likely (HR 0.87, 95% CI (0.78 to 0.97)) to experience cardiovascular events (13%) than patients receiving a placebo and standard of care (14.9%).”
The cited source says what the claim attributes to it.
In the citing paper
“Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) have also been shown to improve kidney outcomes (95-100).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
The cited source says what the claim attributes to it.
In the citing paper
“Liraglutide was also demonstrated to reduce cardiovascular risk in the LEADER trial.9”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Similarly, previously mentioned clinical trials have demonstrated superiority of certain GLP-1 receptor agonists to placebo in reducing the risk of MACE.[7][8][9]”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“As previously discussed, several medications in the SGLT-2 inhibitor and GLP-1 receptor agonist drug classes have been demonstrated to have cardiovascular and renal benefits for patients.[7][8][9][37][38][39]”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Recently, trials evaluating a sodium-glucose cotransporter 2 inhibitor (empagliflozin) and a glucagon-like peptide 1 (GLP-1) analogue (liraglutide) have shown improved cardiovascular outcomes in patients with type 2 diabetes who were at high risk for cardiovascular events.2,3”
From Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (2016) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“To date, two antihyperglycemic agents have been shown to reduce the rate of cardiovascular events in patients with type 2 diabetes at high cardiovascular risk.2,3”
From Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (2016) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“GLP-1 RAs have also been shown to improve kidney outcomes (104-109).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [104]
The cited source says what the claim attributes to it.
In the citing paper
“liraglutide reduced the risk of new or worsening nephropathy (a composite of persistent macroalbuminuria, doubling of serum creatinine, kidney failure, or death from kidney failure) by 22%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [104]
The cited source says what the claim attributes to it.
In the citing paper
“The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial was a randomized, double-blind trial that assessed the effect of liraglutide, a GLP-1 RA, versus placebo on cardiovascular outcomes in 9,340 people with type 2 diabetes at high risk for cardiovascular disease or with cardiovascular disease (261).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [261]
The cited source says what the claim attributes to it.
In the citing paper
“After a median follow-up of 3.8 years, LEADER showed that the primary composite outcome (MI, stroke, or cardiovascular death) occurred in fewer participants in the treatment group (13.0%) than in the placebo group (14.9%) (HR 0.87 [95% CI 0.78-0.97];P < 0.001 for noninferiority; P = 0.01 for superiority).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [261]
The cited source says what the claim attributes to it.
In the citing paper
“Deaths from cardiovascular causes were significantly reduced in the liraglutide group (4.7%) compared with the placebo group (6.0%) (HR 0.78 [95% CI 0.66-0.93];P = 0.007) (261).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [261]
The cited source says what the claim attributes to it.
In the citing paper
“Results of trials with the GLP-1 RAs liraglutide (once daily) and semaglutide, albiglutide, efpeglenatide, and dulaglutide (once weekly) have all shown evidence of a reduction in major atherosclerotic cardiovascular outcomes (MI, stroke, or cardiovascular death) (251–256).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [251]
The cited source says what the claim attributes to it.
In the citing paper
“The clinical trials that may have impacted our results were the CANVAS (canagliflozin, published 2017), EMPA-REG OUTCOME (empagliflozin, 2015), the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial (semaglutide, 2016), and the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEAD”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“The clinical trials that may have impacted our results were the CANVAS (canagliflozin, published 2017), EMPA-REG OUTCOME (empagliflozin, 2015), the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial (semaglutide, 2016), and the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEAD”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [11]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Multiple large CVOTs and kidney outcome trials of SGLT2is have demonstrated robust and consistent reductions in the risk of hospitalization for HF in persons with T2D.239,423,425,426,648”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [423]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Based on the CREDENCE trial,423 the FDA has given canagliflozin an indication to reduce the risk of end-stage kidney disease, doubling of serum creatinine, CV death, and hospitalization for HF in adults with T2D and diabetic nephropathy with albuminuria.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [423]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Although the antihyperglycemic effect can be diminished with decreasing eGFR, studies have shown that SGLT2is continue to exert their renal protective benefit for those with low eGFRs (eg, <45 mL/min/1.73 m2).423”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [423]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Given the additional beneficial effects of GLP-1 RAs and SGLT2 inhibitors on CV outcomes in T2DM (Section 5.3), these agents should be the preferred glucose-lowering medication in overweight and obese patients with CVD and T2DM, as obesity medications have, to date, not shown to reduce CV events.[70][71][72]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [70]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Specifically, compared with placebo, empagliflozin reduced the risk of incident or worsening nephropathy (a composite of progression to UACR >300 mg/g creatinine, doubling of serum creatinine, ESKD, or death from ESKD) by 39%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“and the risk of doubling of serum creatinine accompanied by eGFR #45 mL/min/1.73m 2 by 44%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“canagliflozin reduced the risk of progression of albuminuria by 27%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“and the risk of reduction in eGFR, ESKD, or death from ESKD by 40%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [95]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“empagliflozin reduced the risk of incident or worsening nephropathy (a composite of progression to UACR >300 mg/g creatinine, doubling of serum creatinine, kidney failure, or death from kidney failure) by 39% and the risk of doubling of serum creatinine accompanied by eGFR ≤45 mL/ min/1.73m 2 by 44%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [104]
Experimental — accuracy not yet measuredIn the citing paper
“The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. 33”
From Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials (2025) · cites this paper as [33]
In the citing paper
“Following these regulatory requirements, several cardiovascular outcomes trials (CVOT) have been completed, which demonstrate that certain anti-diabetic treatments are associated with a lower risk of CVD [17–20].”
From Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017 (2018) · cites this paper as [18]
In the citing paper
“Newer antidiabetic drugs have been shown to lower the risk of CVD in T2DM patients [17–20]; however, these drugs are often intended to be used as second- to third-line treatments and many years may pass before patients can benefit.”
From Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017 (2018) · cites this paper as [18]
In the citing paper
“Emerging data support the efficacy of GLP-1RAs, in reducing the incidence of major adverse cardiovascular events (MACEs), preventing the onset of macroalbuminuria and slowing the progression of renal damage toward ESRD [5, 6]”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [6]
In the citing paper
“Emerging data support the efficacy of GLP-1RAs, in reducing the incidence of major adverse cardiovascular events (MACEs), preventing the onset of macroalbuminuria and slowing the progression of renal damage toward ESRD [5, 6]”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [6]
In the citing paper
“Emerging data support the efficacy of GLP-1RAs, in reducing the incidence of major adverse cardiovascular events (MACEs), preventing the onset of macroalbuminuria and slowing the progression of renal damage toward ESRD [5, 6]”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [6]
In the citing paper
“The eGFR decline was slower in the liraglutide group; this effect was most evident in subcategories of patients with moderate (eGFR 30–59 mL/min/1.73 m2) or severe (eGFR <30 mL/min/1.73 m2) CKD.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [6]
In the citing paper
“Regarding the renal composite outcome, in the liraglutide group the incidence of nephropathy was 22% lower than in placebo with a favourable impact especially on macroalbuminuria, while no significant differences were observed about renal hard endpoints.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [6]
In the citing paper
“Regarding the renal composite outcome, in the liraglutide group the incidence of nephropathy was 22% lower than in placebo with a favourable impact especially on macroalbuminuria, while no significant differences were observed about renal hard endpoints.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [6]
In the citing paper
“GLP1-RA have been shown to reduce MACE in patients with T2D with A1c elevation >6.5%, who were at high cardiovascular risk or had established CVD (Table 1) [37], [38], [39], [40], [41].”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [37]
In the citing paper
“Most GLP-1 RAs had a neutral effect on risk of HF hospitalization in the placebo-controlled RCTs assessing CV safety of glucose-lowering medications in patients with T2DM with or at high risk of ASCVD, despite increasing heart rate by 3-5 b.p.m. 70,72,158- 163,544”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [70]
In the citing paper
“GLP-1 RAs (lixisenatide, liraglutide, semaglutide, exenatide ER, dulaglutide, efpeglenatide) have a neutral effect on the risk of HF hospitalization, and should be considered for glucose-lowering treatment in patients with T2DM at risk of or with HF. 70,158-164,545 IIa A”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [70]
In the citing paper
“liraglutide, which reduced MACEs in the LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results), at least in the lower doses used for T2DM”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [17]
In the citing paper
“several cardiovascular outcomes trials (CVOTs) demonstrated that drugs that lowered HbA1c to similar levels had different effects on cardiovascular outcomes”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [17]
In the citing paper
“liraglutide led to a 13% RRR in MACEs (13.0% versus 14.9%)”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [17]
In the citing paper
“and a 22% RRR in cardiovascular death (4.7% versus 6.0%)”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [17]
In the citing paper
“After a median follow-up of 3.8 years, LEADER showed that the primary composite outcome (MI, stroke, or cardiovascular death) occurred in fewer participants in the treatment group (13.0%) when compared with the placebo group (14.9%) (HR 0.87 [95% CI 0.78 -0.97]; P < 0.001 for noninferiority; P = 0.01 for superiority).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [203]
In the citing paper
“Deaths from cardiovascular causes were signi fi cantly reduced in the liraglutide group (4.7%) compared with the placebo group (6.0%) (HR 0.78 [95% CI 0.66 -0.93]; P = 0.007) (203).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [203]
In the citing paper
“No increased risk of heart failure hospitalization has been identi fi ed in the cardiovascular outcomes trials of the GLP-1 receptor agonists lixisenatide, liraglutide, semaglutide, exenatide once-weekly, albiglutide, or dulaglutide compared with placebo ( Table 10.3 B ) (203,204,207 -209).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [203]
In the citing paper
“and four FDA-approved GLP-1 receptor agonists (liraglutide, albiglutide [although that agent was removed from the market for business reasons], semaglutide [lower risk of cardiovascular events in a moderate-sized clinical trial but one not powered as a cardiovascular outcomes trial], and dulaglutide).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [203]
In the citing paper
“Additionally, GLP-1 analogues also appear to decrease the risk of cardiovascular pathology in patients, according to some studies, and preliminary data suggest they do so to a greater degree than other oral glucose-lowering drugs.262,275–277”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [276]
In the citing paper
“Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are the currently most efficacious weight lowering drugs.”
In the citing paper
“The efficacy and safety profile of the GLP1-RAs liraglutide and semaglutide are well-documented, with an average body weight loss of up to 15%, usually transient mild to moderate gastrointestinal side effects, and cardiorenal benefits [6–8].”
In the citing paper
“The LEADER study in high-risk patients with T2D reported that the GLP-1 RA liraglutide improved CVD outcomes (20).”
From Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS (2018) · cites this paper as [20]
In the citing paper
“The LEADER study demonstrated improvement in CVD outcomes despite an increase in the heart rate of 3 bpm (20).”
From Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS (2018) · cites this paper as [20]
In the citing paper
“Compared with other anti-obesity drugs, one of the main benefits of liraglutide is that it does not contribute to the incidence of CVD in obese patients with T2DM [64].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [64]
In the citing paper
“However, a longer duration of 8–15 years after strict glycemic control is necessary for the suppression of ASCVD risk797, 798).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [798]
In the citing paper
“Possible mechanisms of action on the cardiovascular system of GLP-1RAs include anti-inflammatory, antiatherosclerotic, vasodilatory, and other hemodynamic effects, and life-long exposure of GLP-1 is associated with prevention of HF.22, 23, 24”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [23]
In the citing paper
“In addition to providing control of diabetes mellitus, GLP-1 receptor agonists have shown to provide weight loss and cardiovascular protective effects [12–15].”
From Effects of Semaglutide Versus Dulaglutide on Epicardial Fat Thickness in Subjects with Type 2 Diabetes and Obesity (2020) · cites this paper as [13]
In the citing paper
“Clinical trials found that GLP-1 receptor agonists as a class reduced major adverse cardiovascular events [12–15].”
From Effects of Semaglutide Versus Dulaglutide on Epicardial Fat Thickness in Subjects with Type 2 Diabetes and Obesity (2020) · cites this paper as [13]
In the citing paper
“In addition, GLP-1RAs have a favorable safety profile and have been associated with substantial weight loss.4,6,7,9”
From Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review (2020) · cites this paper as [6]
In the citing paper
“GLP-1RA therapy has a favorable safety profile.”
From Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review (2020) · cites this paper as [6]
In the citing paper
“To date, randomized clinical trials of albiglutide, dulaglutide, liraglutide, and injectable semaglutide have reported favorable cardiovascular outcomes.”
From Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review (2020) · cites this paper as [6]
In the citing paper
“Not all DPP4 inhibitors are associated with higher rates of HF (Table 8).16 -24,184-186”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [22]
In the citing paper
“In these trials, GLP-1 receptor agonists had a neutral effect on the risk for HF hospitalization.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [22]
In the citing paper
“SBP was also significantly lower in the liraglutide group.”
From The Vasculature in Prediabetes (2018) · cites this paper as [209]
In the citing paper
“Patients in the liraglutide group lost 2.3 kg more than the placebo treatment group.”
From The Vasculature in Prediabetes (2018) · cites this paper as [209]
In the citing paper
“Importantly, long-acting GLP-1 agonists reduce mortality in patients with T2DM.”
From The Vasculature in Prediabetes (2018) · cites this paper as [209]
In the citing paper
“In the Liraglutide Effect and Action in Diabetes of Cardiovascular Outcomes Results (LEADER) trial, liraglutide 1.8 mg/d reduced the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in patients with T2DM and high cardiovascular risk compared to placebo (from 14.9% to 13%, HR 0.87, 95% CI 0.78-0.97, P=0.01).209”
From The Vasculature in Prediabetes (2018) · cites this paper as [209]
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Twenty-Year Trends in Prevalence and Incidence of Diabetic Retinal Disease
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“30,31 An odd exception to this complication reduction has been DRD, which in some studies was shown to worsen with glucagon-like peptide-1 receptor agonist use.”
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“…large CVOTs—such as LEADER, SUSTAIN-6, REWIND, SELECT, FLOW, and SOUL—have shown that GLP-1RAs significantly reduce the risk of MACE, including nonfatal myocardial infarction, stroke, and cardiovascular death, particularly in individuals with established atherosclerotic CVD (ASCVD) [20, 39, 45–50].”
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“However, the results of the LEADER cardiovascular study [2], which observed vascular benefits in individuals with type 2 diabetes and established, or risk factors for, CVD, may imply that this vascular pathway is intact, although further research is needed to confirm this.”
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“Within the class of GLP1 receptor agonists, a similar difference in outcomes between patients with eCVD and those without eCVD at baseline was shown in the LEADER study [2], which tested liraglutide (p for interaction = 0.”
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“The spike in the 2016 FWCI is driven by an outlier – one highly cited study published with support from NC TraCS [35].”
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“When looked at in more detail in respective trials, the composite renal outcome was to a large extent driven by a reduction of the risk of new onset of persistent macroalbuminuria [15, 17, 19].”
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“Since the EMPA-REG outcome trial was reported, the LEADER trial, the second CVOT with GLP-1RAs, was reported in 2016 [65].”
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“This finding might be attributed to the fact that in our population the proportion of patients on sodium glucose co-transporters 2 (SGLT2) inhibitors [39–41] and GLP1-RA [42, 43] was rather low at baseline.”
BackgroundNew Aspects of Diabetes Research and Therapeutic Development
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Heart Failure Incidence Following ST-Elevation Myocardial Infarction
Costa, R. G., Trêpa, M., Oliveira, M. F., de Frias, A. D., Campinas, A., Luz, A., Santos, M., & Torres, S. (2021) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2021.10.035 · Cited by 28
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The Role of Mitochondrial Biogenesis Dysfunction in Diabetic Cardiomyopathy
Tao, L., Wang, T., Lu, Z., Hua, F., & Li, J. (2022) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2021.192 · Cited by 27
“Furthermore, GLP-1RAs could reduce established CV risk factors in T2DM, such as hyperglycemia, obesity, dysfunctional lipid profile, and high blood pressure (Marso et al., 2016; Kristensen et al., 2019; Verma et al., 2020).”
BackgroundBaylan, U., Korn, A., Emmens, R. W., Schalkwijk, C. G., Niessen, H. W. M., Krijnen, P. A. J., & Şimşek, S. (2022) · European Journal of Clinical Investigation · doi:10.1111/eci.13807 · Cited by 26
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“On the other hand, clinical trials have demonstrated that liraglutide may lead to a series of adverse events, such as hypoglycemia, acute gallstone disease, acute cholecystitis, and the most common and the leading cause of the discontinuation of liraglutide, gastrointestinal disorders (27).”
BackgroundKorayem, G. B., Alshaya, O. A., Alghamdi, A. A., ALANAZI, S., Almutib, R. T., Alsaileek, M., Alrashidi, A., Aldosari, N., Sheraim, N. B., Yami, M. S. A., et al. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.1031306 · Cited by 25
Five-year Weight Loss Maintenance With Obesity Pharmacotherapy
Weintraub, M. A., D’Angelo, D., Tchang, B. G., Sahagun, A., Andre, C., Aronne, L. J., & Shukla, A. P. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad100 · Cited by 31
Management of diabetic kidney disease: where do we stand?: A narrative review
Sindhu, D., Sharma, G. S., & Kumbala, D. R. (2023) · Medicine · doi:10.1097/md.0000000000033366 · Cited by 27
“expression Liraglutide LEADER([40]) Liraglutide slowed the development and progression of DKD than placebo.”
BackgroundWong, N. D., Karthikeyan, H., & Fan, W. (2025) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-023-07488-3 · Cited by 26
Hachuła, M., Kosowski, M., Ryl, S., Basiak, M., & Okopień, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031854 · Cited by 26
“[17–20].”
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“Death from CV causes and all-cause mortality were reduced in participants receiving liraglutide in the LEADER study [42, 43], while the SUSTAIN-6 study demonstrated lower CV deaths in patients receiving subcutaneous semaglutide [44].”
BackgroundKalra, S. (2016) · Diabetes Therapy · doi:10.1007/s13300-016-0197-4 · Cited by 28
“Table 1 summarizes the findings of this study, which revealed a significant 13% reduction in the primary outcome, a significant 22% fall in CV death, and a numerical, but statistically non-significant lowering of risk of non-fatal MI and non-fatal stroke [9].”
BackgroundInfluentialEffects of canagliflozin on cardiovascular risk factors in patients with type 2 diabetes mellitus
Budoff, M. J., & Wilding, J. P. H. (2017) · International Journal of Clinical Practice · doi:10.1111/ijcp.12948 · Cited by 27
Nyström, T., Santos‐Pardo, I., Hedberg, F., Wardell, J., Witt, N., Cao, Y., Bojö, L., Nilsson, B., & JENDLE, J. H. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00325 · Cited by 25
“Although mechanisms behind the CV benefits of the LEADER study remains elusive (2), it is suggested related to the modified atherosclerotic process rather than prompt hemodynamic actions, as suggested for the EMPA-REG OUTCOME trial (33).”
BackgroundInfluentialMasuda, D., Kobayashi, T., Sairyou, M., Hanada, H., Ohama, T., Koseki, M., Nishida, M., Maeda, N., Kihara, S., Minami, T., et al. (2017) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.41343 · Cited by 27
On behalf of the NN2211-4118 Study Group, Lapolla, A., Berra, C., Boemi, M., Bossi, A. C., Candido, R., Cianni, G. D., Frontoni, S., Genovese, S., Ponzani, P., et al. (2017) · Advances in Therapy · doi:10.1007/s12325-017-0652-2 · Cited by 26
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Inpatient Glycemic Management in the Setting of Renal Insufficiency/Failure/Dialysis
Iyengar, R., Franzese, J., & Gianchandani, R. Y. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1044-y · Cited by 28
Tao, L., Wang, L., Yang, X., Jiang, X., & Hua, F. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.11.015 · Cited by 26
Wright, L. A.-C., & Hirsch, I. B. (2019) · Diabetic Medicine · doi:10.1111/dme.13941 · Cited by 26
Mahdi, A., Jiao, T., Yang, J., Kövamees, O., Alvarsson, M., von Heijne, M., Zhou, Z., & Pernow, J. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00861 · Cited by 26
Mortensen, M. B., Blaha, M. J., & Nordestgaard, B. G. (2020) · JAMA Cardiology · doi:10.1001/jamacardio.2019.4759 · Cited by 27
Cardiovascular Risks and Benefits of Medications Used for Weight Loss
Bramante, C. T., Raatz, S. J., Bomberg, E. M., Bensignor, M. O., & Ryder, J. R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00883 · Cited by 27
“8mg daily for diabetes treatment in high-risk cardiovascular patients (11).”
BackgroundAdvances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes
Libianto, R., Davis, T. M. E., & Ekinci, E. I. (2020) · The Medical Journal of Australia · doi:10.5694/mja2.50472 · Cited by 26
Acid-base and electrolyte disorders associated with the use of antidiabetic drugs
Filippatos, T. D., Tzavella, E., Rizos, C. V., Elisaf, M., & Liamis, G. L. (2017) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1361400 · Cited by 27
Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease
Aguilar, D. A. (2016) · Circulation Heart Failure · doi:10.1161/circheartfailure.116.003316 · Cited by 25
Pratley, R. E., Husain, M., Lingvay, I., Pieber, T. R., Mark, T., Saevereid, H. A., Møller, D. V., Zinman, B., & the DEVOTE Study Group (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0960-8 · Cited by 25
Self-citationChou, C., & Chuang, S. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13314 · Cited by 25
Investigational glucagon-like peptide-1 agonists for the treatment of obesity
Tomlinson, B., Hu, M., Zhang, Y., Chan, P., & Liu, Z.-M. (2016) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2016.1221925 · Cited by 25
“8 mg daily compared to placebo in 9340 high-CV-risk T2DM patients [124].”
BackgroundWharton, S., Rosenstock, J., Konige, M., Lin, Y., Duffin, K., Wilson, J., Banerjee, H., Pirro, V., Kazda, C., & Mather, K. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02781-x · Cited by 26
“For example, in participants with type 2 diabetes, treatment with dulaglutide reduced the risk of CV death, myocardial infarction, or non-fatal stroke by 12%, while liraglutide produced a 13% reduction an analogous 3-point composite MACE [4, 5].”
InfluentialTobaiqy, M. (2024) · Pharmacological Reports · doi:10.1007/s43440-024-00629-x · Cited by 25
“[ 3].”
InfluentialTreatment and practical considerations of diabetic kidney disease
Bilen, Y., Almoushref, A., Alkwatli, K., Osman, O., Mehdi, A., & Sawaf, H. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1264497 · Cited by 28
Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective
Olivieri, A., Muratov, S., Larsen, S., Luckevich, M., Chan, K., Lamotte, M., & Lau, D. C. W. (2024) · International Journal of Obesity · doi:10.1038/s41366-024-01467-w · Cited by 34
“A long-term CVOT (LEADER trial) of patients with T2D and at a high-risk of having CV-events showed superiority of liraglutide 1.8 mg over the placebo in the primary outcome (e.g., time of CV death, non-fatal MI, and non-fatal stroke) [28].”
BackgroundInfluentialMałyszczak, A., Przeździecka-Dołyk, J., Szydełko-Paśko, U., & Misiuk‐Hojło, M. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13061797 · Cited by 29
Rethinking weight loss treatments as cardiovascular medicine in obesity, a comprehensive review
Tuccinardi, D., Watanabe, M., Masi, D., Monte, L., Meffe, L. B., Cavallari, I., Nusca, A., Maddaloni, E., Gnessi, L., Napoli, N., et al. (2024) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwae171 · Cited by 30
Lai, H.-W., See, C. Y., Chen, J.-Y., & Wu, V.-C. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02364-2 · Cited by 25
“…(Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial, which included patients with chronic kidney disease (CKD), which proved the efficacy of liraglutide in reducing the incidence of death from CV causes, nonfatal myocardial infarction (MI) and stroke [7].”
BackgroundInfluentialAgrawal, V., Amasa, S., Karabacak, M., & Margetis, K. D. (2024) · Neurosurgery · doi:10.1227/neu.0000000000003291 · Cited by 27
Khadke, S., Kumar, A., Bhatti, A. W., Dani, S. S., Al-Kindi, S. G., Nasir, K., Virani, S. S., Upadhyay, J., Garcia-Banigan, D. C., Abraham, S., et al. (2024) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2024.10.448 · Cited by 27
Comprehensive treatment of diabetic endothelial dysfunction based on pathophysiological mechanism
Liu, Z., Lu, J., Sha, W., & Lei, T. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1509884 · Cited by 34
“The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) (93) and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) (94) have demonstrated a reduction in the risk of MACE, thereby supporting the ca…”
Renoprotective mechanisms of glucagon-like peptide-1 receptor agonists
Chen, J., Cooper, M., & Coughlan, M. T. (2025) · Diabetes & Metabolism · doi:10.1016/j.diabet.2025.101641 · Cited by 32
Insulin Resistance and Insulin Handling in Chronic Kidney Disease
Parvathareddy, V. P., Wu, J., & Thomas, S. S. (2023) · Comprehensive physiology · doi:10.1002/j.2040-4603.2023.tb00281.x · Cited by 28
“Liraglutide improves cardiovascular and microvascular outcomes, including kidney disease, in people with diabetes (48) GLP1 receptor agonists improved IR in both animal models and humans (87).”
Heo, K., Phan, L. P., Le, N. T. T., & Jin, Y. (2025) · Archives of Pharmacal Research · doi:10.1007/s12272-025-01542-4 · Cited by 29
“SGLT2 inhibitors increase glucose excretion in the urine by inhibiting this protein, leading to reduced blood glucose levels and improved glycemic control, particularly in patients with T2DM (Heerspink et al. 2016; Cowie and Fisher 2020).”
InfluentialGlucagon-like peptide-1 receptor agonists in arthritis: current insights and future directions
Karacabeyli, D., & Lacaille, D. V. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01302-0 · Cited by 31
Ramírez-Mejía, M. M., Ponciano‐Rodríguez, G., Eslam, M., & Méndez-Sánchez, N. (2025) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188251406456 · Cited by 35
Rinella, M. E., & Sookoian, S. C. (2026) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-026-01187-8 · Cited by 31
“Large cardiovascular outcome trials in populations with T2D have demonstrated that several GLP1-RAs, including semaglutide, reduce the risk of major adverse cardiovascular events by 12–26% relative to placebo 68,69 .”
Gargiulo, P., Savarese, G., D’Amore, C., Martino, F. D., Lund, L. H., Marsico, F., Dellegrottaglie, S., Marciano, C., Trimarco, B., & Filardi, P. P. (2017) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2017.09.006 · Cited by 25
Kugler, A. J., & Thiman, M. (2018) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s134960 · Cited by 24
Renal Outcomes of Antidiabetic Treatment Options for Type 2 Diabetes—A Proposed MARE Definition
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Igel, L. I., Saunders, K. H., & Fins, J. J. (2018) · Current Atherosclerosis Reports · doi:10.1007/s11883-018-0740-z · Cited by 25
Philis‐Tsimikas, A., Wysham, C., Hardy, E., Han, J., & Iqbal, N. (2018) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2018.11.012 · Cited by 25
Residual cardiovascular risk among people with diabetes
Dash, S., & Leiter, L. A. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13646 · Cited by 27
5 Conservative treatment for PAD – Risk factor management
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Computing and interpreting the Number Needed to Treat for Cardiovascular Outcomes Trials
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“3) [18, 19, 22–29].”
Gür, F. M., & Aktaş, İ. (2021) · Tissue and Cell · doi:10.1016/j.tice.2021.101582 · Cited by 26
Myeloid cells in retinal and brain degeneration
Guo, M., Schwartz, T. D., Dunaief, J. L., & Cui, Q. N. (2021) · FEBS Journal · doi:10.1111/febs.16177 · Cited by 25
GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events
de Mortanges, A. P., Sinaci, E., Salvador, D., Bally, L., Muka, T., Wilhelm, M., & Bano, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.856111 · Cited by 25
“Coronary Revascularization Procedures Trials including LEADER, AMPLITUDE-O, and REWIND found no effect of GLP-1 RAs on the risk of coronary revascularization (Marso et al., 2016; Gerstein et al., 2019, 2021).”
Janić, M., Rizzo, M., Cosentino, F., Stoian, A. P., Lunder, M., Šabović, M., & Janež, A. (2022) · Diabetes Therapy · doi:10.1007/s13300-022-01226-y · Cited by 27
“This benefit is in line with the proposed direct anti-atherosclerotic action of liraglutide, which showed cardiovascular benefit in the LEADER trial [18], since evidence from preclinical and clinical studies suggest that this GLP-1 receptor agonist can reduce atherosclerosis formation and progression [19].”
ResultSchnell, O., Standl, E., Catrinoiu, D., Genovese, S., Lalic, N. M., Lalic, K. S., Škrha, J., Valensi, P. E., & Ceriello, A. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0667-2 · Cited by 25
Diabesity in Elderly Cardiovascular Disease Patients: Mechanisms and Regulators
García‐Vega, D., González‐Juanatey, J. R., & Eirás, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147886 · Cited by 26
“The clinical trial LEADER has demonstrated a cardiovascular benefit of liraglutide in patients with T2DM because it reduced 13% of nonfatal myocardial infarction or stroke and 22% of cardiovascular death [218].”
BackgroundEmerging drugs for the treatment of diabetic nephropathy
Kim, Y. K., Ning, X., Munir, K. M., & Davis, S. N. (2022) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2022.2155632 · Cited by 25
Khedagi, A. M., Hoke, C., Kelsey, M. D., Coviello, A. D., Jones, W. S., Jackson, L. R., Patel, M. R., McGarrah, R. W., Pagidipati, N. J., & Shah, N. P. (2023) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2023.100477 · Cited by 28
SGLT2 Inhibitors: Effect on Myocardial Infarction and Stroke in Type 2 Diabetes
Mukhopadhyay, P., Sanyal, D., Chatterjee, P., Pandit, K., & Ghosh, S. K. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad113 · Cited by 27
Metadata
- Authors
- Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., Steinberg, W. M., Stockner, M., Zinman, B., Bergenstal, R. M., & Buse, J. B.
- Affiliations
- Cleveland Clinic (US)
- Mount Sinai Hospital (CA)
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-07-28
- Volume
- 375
- Issue
- 4
- Pages
- 311-322
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4985288
- OpenAlex
- W2425644022
- Cited by
- 7,629
- References
- 25
- Citations by year
- 2026: 834 · 2025: 809 · 2024: 643 · 2023: 602 · 2022: 639 · 2021: 745 · 2020: 845 · 2019: 769 · 2018: 814 · 2017: 675 · 2016: 244
- FWCI
- 837.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (acceptedVersion, other-oa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Digital Collections portal (Koç University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Celgene
- Massachusetts Medical Society
- Intarcia Therapeutics
- Orexigen Therapeutics
- ResMed
- Novo Nordisk
- Esperion Therapeutics
- National Institutes of Health (UL1TR001111, UL1TR002489)
- Relypsa
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- type 2 diabetes, cardiovascular outcomes, GLP-1 receptor agonists, myocardial infarction, stroke, cardiovascular mortality, heart failure hospitalization, pancreatitis, gastrointestinal adverse effects, non-inferiority, high cardiovascular risk patients, GLP-1 receptor antagonists
- MeSH terms
- Liraglutide, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Gastrointestinal Diseases, Humans, Hypoglycemic Agents, Male, Middle Aged, Myocardial Infarction, Treatment Outcome, Stroke
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