The DOI matches its Crossref record; 59 of the 63 references it cites were found in a registry or an index; 17 of the 45 sources its claims cite were checked for support.
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
Open accessAbstract
BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). CONCLUSIONS: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
22 Own method · 17 Own result · 12 No full text of the sources · 6 Own interpretation · 5 Supported so far · 5 Partly supported · 4 Supported · accuracy not yet measured
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
“In ancillary analyses, the effect of pioglitazone on the primary outcome was similar when stroke and myocardial infarction were defined according to updated criteria28,29 (hazard ratio, 0.73; 95% CI, 0.60 to 0.88).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > CLINICAL OUTCOMES
What the sources say
- Not checked — no full text of the sourcecites [28] source
- Supportedcites [29] source
The citation is attached to the updated myocardial-infarction criteria, not to the pioglitazone hazard ratio. The paper’s “Biomarker Detection of Myocardial Injury With Necrosis” section specifies diagnostic criteria for acute MI, including a rise or fall in cardiac troponin and a value above the decision threshold. (LLM, conf=0.92)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The presence of insulin resistance increases the risk of vascular disease, possibly because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity.7–9”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > Abstract > CONCLUSIONS
What the sources say
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The opening section links insulin resistance to increased cardiovascular mortality and endothelial dysfunction. Figure 1 describes a possible prothrombotic pathway, and the main text associates inflammation with vascular dysfunction. The paper does not support the full proposed list of mediators: it does not identify hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, or increased platelet reactivity as explanations for the higher vascular risk. (LLM, conf=0.88)
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) associates insulin resistance with vascular disease and describes dyslipidemia and other metabolic abnormalities as part of a proatherogenic milieu. The “Hyperglycemia and hypertension” section (page unavailable) discusses elevated glucose and compensatory hyperinsulinemia, while noting that the relationship with hypertension is less clear. Our copy does not support the full proposed list of mediators, particularly hypercoagulability and increased platelet reactivity. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [9] source
hedgedconditional- 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because insulin sensitivity may be transiently impaired after a stroke,21 the screening blood test was conducted at least 14 days after the index event.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > TRIAL PATIENTS
What the sources say
- Supportedcites [21] source
The Discussion describes transient resistance to endogenous insulin in patients who developed glucose intolerance two weeks after stroke. It also reports that their altered glucose-insulin response returned to normal by the end of the fourth week. This supports the hedged claim that insulin sensitivity may be transiently impaired after a stroke. (LLM, conf=0.94)
hedgedconditional- 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.
- 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
“The presence of insulin resistance increases the risk of vascular disease, possibly because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity.7–9”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > Abstract > CONCLUSIONS
What the sources say
- Supportedcites [7] source
The opening passage states that insulin resistance is associated with a two- to threefold increased risk of cardiovascular mortality. The concluding passage also refers to the risk of insulin resistance-associated vascular disease. These support the cited risk statement, though the paper describes an association rather than establishing causation. (LLM, conf=0.90)
- Supportedcites [8] source
The Abstract states that considerable evidence links insulin resistance with vascular disease and describes insulin resistance as part of a proatherogenic milieu. The Dyslipidemia in insulin resistance section explains how it produces a lipid profile associated with atherosclerotic risk. The paper does not establish that insulin resistance in the vascular wall itself causes atherosclerosis, but that qualification does not undermine the stated risk association. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [9] source
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The finding for diabetes was also unchanged when a cutoff for glycated hemoglobin of 6.5% or more was used in local analysis, consistent with the 2010 ADA recommendation30 (hazard ratio, 0.49; 95% CI, 0.38 to 0.64).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > CLINICAL OUTCOMES
What the sources say
- Supportedcites [30] source
The citation supports the ADA cutoff, not the citing authors’ local-analysis result or hazard ratio. In Classification and Diagnosis > Recommendations (page unavailable), the ADA affirms A1C ≥6.5% as a diagnostic threshold and lists it among the criteria for diagnosing diabetes. (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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, more recent studies48,49 showed no significant association for any dose or duration of therapy.49”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Partly supportedcites [48] sourceExperimental — accuracy not yet measured
The Results (p. 5) report no significant association with cumulative exposure, and the duration categories of 1–2 and more than 2 years also have confidence intervals spanning 1. The paper does not report a dose-specific analysis, so it does not support the claim’s “any dose” wording. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [49] source
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
“These actions modulate the transcription of genes with favorable effects on insulin sensitivity,13,36 fat distribution,37 plasma glucose,35,38 lipid and protein metabolism,36,38 vascular endothelial function,39 and inflammation.35,40”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [13] source
- Not checked — no full text of the sourcecites [36] source
- Not checked — no full text of the sourcecites [35] source
- Supportedcites [40] source
This source is cited for the inflammation portion of the sentence. The Results (pp. 6–7) report that pioglitazone reduced adipose-tissue expression of CD68 and MCP-1 and lowered plasma TNFα; the Discussion (p. 8) describes these findings as consistent with anti-inflammatory effects. (LLM, conf=0.91)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI-2D) trial,31 the rate of primary outcome of death, stroke, or myocardial infarction was not significantly lower among patients receiving rosiglitazone and metformin (insulin-sparing strategy) than among those receiving insulin and sulfonylurea therapy (insulin-providing strategy).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Partly supportedcites [31] sourceExperimental — accuracy not yet measured
The Results (Primary and Principal Secondary Outcomes; page unavailable) report no significant difference in major cardiovascular events between the insulin-sensitization and insulin-provision groups (P=0.13). But the Methods (Evaluation of Outcomes; page unavailable) define death, myocardial infarction, or stroke as the principal secondary end point, not the primary end point, which was death from any cause. The Methods (Treatment Strategies; page unavailable) also describe randomized treatment strategies that allowed drugs from the other strategy, rather than a direct comparison of the named drug combinations. (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.
- 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
“By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007).”
- Also stated in: § CLINICAL OUTCOMES · plain
“The primary outcome of stroke or myocardial infarction occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007) (Table 2 and Fig. 1, and Table S5 in the Supplementary Appendix).”
- Also stated in: § DISCUSSION · plain
“In this trial involving patients without diabetes who had a recent history of ischemic stroke or TIA and who had insulin resistance, the rate of the primary outcome was lower among patients who received pioglitazone than among those who received placebo.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > Abstract > RESULTS
plainn = 1,939- 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.
- Also stated in: § CLINICAL OUTCOMES · plain
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
“Pioglitazone had no significant effect on cognition, as compared with placebo. The overall between-group difference in the change from baseline in the least-squares mean score on the Modified Mini–Mental State Examination was −0.02 (95% CI, −0.33 to 0.28; P = 0.88).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > CLINICAL 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.
- Probably not a substantial claim. 27
- It may state two separate claims as one. 21
Every source the paper cites for this claim was checked and supports it.
In the paper
“The design of this international, double-blind, placebo-controlled clinical trial has been reported previously.17”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > TRIAL DESIGN AND OVERSIGHT
What the sources say
- Supportedcites [17] source
The DESIGN > Study Objective passage explicitly describes IRIS as an “international, multicenter, randomized, double-blind, placebo-controlled study.” The Study procedures passage also describes assignment to pioglitazone or matching placebo. (LLM, conf=0.95)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The thiazolidinedione class of peroxisome proliferator–activated receptor γ (PPAR-γ) agonists are among the most potent insulin-sensitizing drugs available.14”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > Abstract > CONCLUSIONS
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Discussion (page not specified) reports that troglitazone increased insulin-mediated peripheral glucose disposal substantially more than metformin in a small group of patients with type II diabetes. It does not establish that thiazolidinediones as a class are among the most potent insulin-sensitizing drugs available or discuss their PPAR-γ mechanism. (LLM, conf=0.84)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Observational research conducted in 2011 and 2012 suggested that pioglitazone may increase the risk of bladder cancer.46,47”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Supportedcites [46] source
The Abstract Results report increased bladder-cancer risk among patients who used pioglitazone for more than 24 months, and the Abstract Conclusions describe the association as weak. This 2011 observational cohort study therefore supports the hedged claim, though it found no increased risk with short-term use. (LLM, conf=0.92)
- Supportedcites [47] source
The Results section (page unavailable) reports that pioglitazone exposure was significantly associated with incident bladder cancer in this population-based cohort. That finding supports the citing sentence’s hedged statement that observational research suggested an increased risk. (LLM, conf=0.93)
hedgedconditional- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, the IRIS results are consistent with findings regarding a secondary outcome in the PROactive trial (i.e., that the rates of death, myocardial infarction, or stroke were significantly lower with pioglitazone than with placebo) and with findings of trials showing a favorable effect of pioglitazone on the progression of subclinical atherosclerosis among patients with and those without”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [32] source
- Not checked — no full text of the sourcecites [33] source
- Partly supportedcites [34] sourceExperimental — accuracy not yet measured
The Discussion reports a reduction in PROactive’s secondary composite cardiovascular endpoint and describes slower atherosclerosis progression with pioglitazone in trials involving people with and without type 2 diabetes. It does not specify that PROactive’s secondary endpoint comprised death, myocardial infarction, or stroke, so that detail cannot be verified from this paper. (LLM, conf=0.84)
plaindirect- 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 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
“Other research suggests that PPAR-γ agonists might prevent certain cancers.50,51”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [50] source
- Supportedcites [51] source
The Conclusions state that thiazolidinediones, which are PPARγ agonists, may be associated with a decreased risk of colorectal cancer in patients with diabetes. This supports the citing sentence’s hedged claim that these agonists might prevent certain cancers. No page number is provided in our copy. (LLM, conf=0.91)
hedgedconditional- 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 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
“We selected this measurement because it is easy to perform and is closely correlated with more definitive but complex tests.20,52”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [20] source
- Supportedcites [52] source
The Discussion (page unavailable) describes HOMA-IR as a simple index derived from fasting measurements and says it has robust correlations with directly measured insulin sensitivity. The paper compares such indexes with the more complex euglycemic-hyperinsulinemic clamp, supporting the stated reason for choosing HOMA-IR. (LLM, conf=0.88)
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.
Probably not a substantial claim. 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 total of 3895 patients were enrolled, with 67% from sites in the United States (Fig. S1 in the Supplementary Appendix).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
plainn = 3,895- 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
“According to the 2010 criteria of the ADA (which include a glycated hemoglobin level of ≥6.5% as diagnostic of diabetes), diabetes was present in 116 of 1939 patients (6.0%) in the pioglitazone group and in 129 of 1937 (6.7%) in the placebo group (Table S2 in the Supplementary Appendix).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
plainn = 1,939- 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
“After 1 year, the HOMA-IR index and C-reactive protein level were lower in the pioglitazone group than in the placebo group (Table S6 in the Supplementary Appendix).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > CLINICAL 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
“Patients in the pioglitazone group had more weight gain, edema, shortness of breath, and bone fractures than did patients in the placebo group (Table 3, and Table S7 in the Supplementary Appendix).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > SAFETY 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
“During the trial, levels of fasting glucose, fasting triglycerides, and systolic blood pressure were also lower in the pioglitazone group, as was diastolic blood pressure in years 1 to 4.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > CLINICAL OUTCOMES
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.
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 was no significant between-group difference in the incidence of other monitored adverse events, with the exception of a change in the alanine aminotransferase level, which was more favorable with pioglitazone.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > SAFETY 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
“Among the patients in the pioglitazone group, 52.2% gained more than 4.5 kg and 11.4% gained more than 13.6 kg; the corresponding percentages in the placebo group were 33.7% and 4.5%.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > SAFETY 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.
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
“All outcomes and selected safety events (i.e., bone fracture, macular edema, and cancer) were adjudicated by the members of independent committees in a blinded fashion.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > TRIAL 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
“The P value for the primary outcome was adjusted for interim monitoring with the use of East software, version 6.3 (Cytel), and the P values for the five prespecified time-to-event secondary outcomes were adjusted for multiple testing with the Hochberg procedure and a family-wise error rate of 0.05.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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. 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
“Patients in the pioglitazone group had lower adherence to the drug regimen than did those in the placebo group (Table S4 in the Supplementary Appendix); at the exit visit, 60% of the patients in the pioglitazone group were still taking pioglitazone and 67% in the placebo group were still taking placebo.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
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.
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
“No other outcomes were prespecified.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > TRIAL OUTCOMES
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
“The 19 patients at this site were removed from the study, resulting in a final cohort of 3876 patients (1939 in the pioglitazone group and 1937 in the placebo group).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
plainn = 3,876- 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.
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 provided written informed consent.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > TRIAL PATIENTS
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
“All analyses were performed on an intention-to-treat basis.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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
“Trial operations were approved by the local ethics committee at each site.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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.
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
“We determined that enrollment of 3136 patients would provide a power of 90% to detect a 4-year cumulative rate of stroke or myocardial infarction that was 20% lower in the pioglitazone group than in the placebo group, assuming a two-sided type I error of 0.05 and a 27% outcome rate in the placebo group.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > STATISTICAL ANALYSIS
plaindirectn = 3,136- 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
“Baseline features were similar for patients who were lost to follow-up in the two groups.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
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
“Representatives of Takeda were provided with a copy of the protocol (available at NEJM.org) and manuscript but had no role in the development of the protocol, the conduct of the trial, the interpretation of the data, or the preparation of the manuscript.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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
“Eligible patients were randomly assigned in a 1:1 ratio to receive either pioglitazone or matching placebo.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > TRIAL PROCEDURES
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
“The study was conducted and reported with fidelity to the protocol.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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.
In the paper
“Four interim analyses of the primary outcome were conducted for efficacy and futility with the use of the O’Brien–Fleming method.19”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > METHODS > STATISTICAL ANALYSIS
What the sources say
- Not checked — no full text of the sourcecites [19] 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.
In the paper
“Insulin resistance is nearly universal in patients with type 2 diabetes but is also present in more than 50% of patients without diabetes who have had an ischemic stroke or a TIA.6”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > Abstract > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [6] source
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.
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 trial was monitored by an independent data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke, which funded the study.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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.
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 reasons for drug discontinuation were similar in the two groups, except that more patients in the pioglitazone group than in the placebo group stopped because of edema or weight gain (172 patients vs. 51 patients) or were removed for safety reasons (primarily heart failure, repeated fracture, and incidence of or risk factors for bladder cancer) (146 patients vs. 117 patients).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
plainn = 172- 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.
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
“During a median follow-up of 4.8 years, a total of 227 patients (5.9%) withdrew consent and 99 (2.6%) were lost-to-follow-up (Fig. S1 in the Supplementary Appendix).”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
plainn = 227- 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
“Alleged irregularity in the informed-consent process at one institution resulted in halting of local research activities while the data were still blinded.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > RESULTS > TRIAL POPULATION
hedgeddirect- 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
“Although we did not observe a significant effect of treatment on the incidence of total or any specific cancer, our study was not powered to address these questions.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > 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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The mechanism is uncertain, and studies have not shown a consistent effect of the drug on bone density.44,45”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
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.
In the paper
“Weight gain with PPAR-γ agonists, such as pioglitazone, reflects an increase in adipose tissue mass and a tendency for fluid accumulation owing to renal sodium retention.41”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [41] source
plaindirect- 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 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, other measured and unmeasured effects may have contributed to the benefit of the drug with respect to our primary outcome.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
hedgedconditional- 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.
In the paper
“Sodium retention, if unchecked, can also increase the risk of heart failure.42”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [42] source
plainconditional- 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.
In the paper
“Pioglitazone activates PPAR-γ and also causes partial activation of PPAR-α.35”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [35] source
plaindirect- 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 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, in the IRIS trial, we did not observe a greater incidence of heart failure in the pioglitazone group than in the placebo group, which was probably because we excluded patients with a history of heart failure and used safety algorithms that triggered dose reduction for excessive weight gain or edema.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
hedgedconditional- 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.
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
“To account for this, all HOMA-IR testing in the IRIS trial was performed in central laboratories.”
§ Pioglitazone after Ischemic Stroke or Transient Ischemic Attack > DISCUSSION
plaindirect- 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 authors state this as an assumption.
Data were missing at random for the cognitive function analysis.
“We used a repeated-measures covariance-pattern model on the assumption that data were missing at random to analyze the effect of treatment on cognitive function”
The paper relies on this without support.
Missing time-to-event data were noninformative censoring.
“Missing time-to-event data were treated as noninformative censoring.”
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
“A 2021 meta-analysis analyzed 7 RCTs (N 56,005 participants) with 174,163 patient years of follow-up and found that GLP-1 RAs reduced nonfatal stroke (RR, 0.85; 95% CI, 0.77–0.95) without statistically significant heterogeneity among the trials.660”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [660]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“However, these bene fi ts must be balanced against possible side effects of fl uid retention and congestive HF (196,197,202), weight gain (196 -198,202,203), and bone fracture (204,205).”
The cited source says what the claim attributes to it.
In the citing paper
“In the Insulin Resistance Intervention After Stroke (IRIS) study in adults without diabetes but with insulin resistance (HOMA of insulin resistance > 3.0) and recent history of stroke or transient ischemic attack, there was a lower risk of stroke or myocardial infarction with pioglitazone versus placebo (198,199).”
In the citing paper
“The Insulin Resistance Intervention After Stroke trial reported no significant difference in cognition, measured by Modified Mini-Mental State Examination, associated with pioglitazone compared with placebo over a mean follow-up of 57.6 months.48”
From Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis (2025) · cites this paper as [48]
In the citing paper
“in IRIS, there was no increased risk of heart failure hospitalizations with pioglitazone, but patients with known heart failure were excluded, and there were protocols in place for study drug dose reduction with any signs of fluid overload”
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 [212]
In the citing paper
“in the IRIS trial (Insulin Resistance Intervention After Stroke), which involved 3876 patients with stroke and insulin resistance (but notably not T2DM), pioglitazone produced a 24% RRR in stroke or myocardial infarction (9.0% versus 11.8%)”
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 [212]
Citations
Cites
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1992) · Springer series in statistics · doi:10.1007/978-1-4612-4380-9_25 · Cited by 45,239
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,772
Diagnosis and Classification of Diabetes Mellitus
American Diabetes Association (2010) · Diabetes Care · doi:10.2337/dc11-s062 · Cited by 14,094
Zhang, Q., Wang, C., Zheng, M., Li, Y., Li, J., Zhang, L., Shang, X., & Yan, C. (2014) · Cerebrovascular Diseases · doi:10.1159/000369778 · Cited by 11,609
Third universal definition of myocardial infarction
the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Thygesen, K., Alpert, J. S., Jaffe, A. S., Simoons, M. L., CHAITMAN, B. R., & White, H. D. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.122 · Cited by 6,585
Kernan, W. N., Ovbiagele, B., Black, H. R., Bravata, D. M., Chimowitz, M. I., Ezekowitz, M. D., Fang, M. C., Fisher, M., Furie, K. L., Heck, D. V., et al. (2014) · Stroke · doi:10.1161/str.0000000000000024 · Cited by 5,170
Self-citationA sharper Bonferroni procedure for multiple tests of significance
HOCHBERG, Y. (1988) · Biometrika · doi:10.1093/biomet/75.4.800 · Cited by 4,829
Research works printed but not linked: 1
- Teng EL, 1987, J Clin Psychiatry, 48, 314
Cited by
Sorted by citations
Davies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetes Care · doi:10.2337/dci18-0033 · Cited by 3,518
Self-citationKleindorfer, D. O., Towfighi, A., Chaturvedi, S., Cockroft, K. M., Gutierrez, J., Lombardi-Hill, D., Kamel, H., Kernan, W. N., Kittner, S. J., Leira, E. C., et al. (2021) · Stroke · doi:10.1161/str.0000000000000375 · Cited by 3,237
Self-citationRinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., et al. (2022) · Diabetes Care · doi:10.2337/dci22-0034 · Cited by 2,104
Stroke risk factors, genetics, and prevention
Boehme, A. K., Esenwa, C., & Elkind, M. S. V. (2017) · Circulation Research · doi:10.1161/circresaha.116.308398 · Cited by 1,952
Davies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetologia · doi:10.1007/s00125-018-4729-5 · Cited by 1,455
Self-citationHankey, G. J. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30962-x · Cited by 1,311
Clinical Update: Cardiovascular Disease in Diabetes Mellitus
Wang, C. C. L., Hess, C. N., Hiatt, W. R., & Goldfine, A. B. (2016) · Circulation · doi:10.1161/circulationaha.116.022194 · Cited by 1,222
Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05787-2 · Cited by 1,048
Cusi, K., Isaacs, S., Barb, D., Basu, R., Caprio, S., Garvey, W. T., Kashyap, S., Mechanick, J. I., Mouzaki, M., Nadolsky, K., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.03.010 · Cited by 1,021
COVID-19 and diabetes mellitus: from pathophysiology to clinical management
Lim, S. K., Bae, J. H., Kwon, H., & Nauck, M. A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00435-4 · Cited by 1,061
PPAR control of metabolism and cardiovascular functions
Montaigne, D., Butruille, L., & Staels, B. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00569-6 · Cited by 981
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2016) · Endocrine Practice · doi:10.4158/ep151126.cs · Cited by 879
Stefan, N., Häring, H., & Cusi, K. J. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30154-2 · Cited by 874
Targher, G., Byrne, C. D., & Tilg, H. (2020) · Gut · doi:10.1136/gutjnl-2020-320622 · Cited by 879
“122 123 A large umbrella review recently confirmed that pioglitazone significantly decreased risk of major CVD events but increased risk of heart failure.”
PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
Gross, B., Pawlak, M., Lefebvre, P., & Staels, B. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.135 · Cited by 778
Packer, M. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.03.509 · Cited by 656
Heart Failure in Type 2 Diabetes Mellitus
Kenny, H., & Abel, E. D. (2019) · Circulation Research · doi:10.1161/circresaha.118.311371 · Cited by 682
Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy
Lu, X., Xie, Q., Pan, X., Zhang, R., Zhang, X., Peng, G., Zhang, Y., Shen, S., & Tong, N. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01951-9 · Cited by 895
Diabetes and Stroke: Epidemiology, Pathophysiology, Pharmaceuticals and Outcomes
Chen, R., Ovbiagele, B., & Feng, W. (2016) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2016.01.011 · Cited by 678
Stroke Epidemiology and Risk Factor Management
Guzik, A. K., & Bushnell, C. (2017) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000416 · Cited by 685
Joseph, J. J., Deedwania, P., Acharya, T., Aguilar, D., Bhatt, D. L., Chyun, D. A., Di Palo, K. E., Golden, S. H., Sperling, L. S., & on behalf of the American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, T. A. V. B. C. O. C. C. A. C. O. H. (2022) · Circulation · doi:10.1161/cir.0000000000001040 · Cited by 660
Kanwal, F., Shubrook, J. H., Adams, L. A., Pfotenhauer, K., Wai-Sun Wong, V., Wright, E., Abdelmalek, M. F., Harrison, S. A., Loomba, R., Mantzoros, C. S., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.049 · Cited by 618
Garber, A. J., Handelsman, Y., Grunberger, G., Einhorn, D., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bush, M. A., DeFronzo, R. A., Garber, J. R., et al. (2020) · Endocrine Practice · doi:10.4158/cs-2019-0472 · Cited by 598
Lotta, L. A., Gulati, P., Day, F. R., Payne, F., Ongen, H., van de Bunt, M., Gaulton, K. J., Eicher, J. D., Sharp, S. J., Luan, J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3714 · Cited by 599
Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents
Di Pino, A., & DeFronzo, R. A. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00141 · Cited by 535
Dysregulated lipid metabolism links NAFLD to cardiovascular disease
Deprince, A., Haas, J. T., & Staels, B. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101092 · Cited by 576
“While long-term rosiglitazone treatment of T2D patients may slightly increase the risk of myocardial infarction [164], pioglitazone somewhat decreases the risk of MACE (although the risk of heart failure increases with all glitazones) [165,166].”
BackgroundGarber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2018) · Endocrine Practice · doi:10.4158/cs-2017-0153 · Cited by 503
Blonde, L., Umpierrez, G. E., Reddy, S. S., McGill, J. B., Berga, S. L., Bush, M., Chandrasekaran, S., DeFronzo, R. A., Einhorn, D., Galindo, R. J., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.08.002 · Cited by 507
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 545
Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management
Ma, C.-X., Ma, X.-N., Guan, C.-H., Li, Y.-D., Mauricio, D., & Fu, S.-B. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01516-6 · Cited by 464
8. Pharmacologic Approaches to Glycemic Treatment
American Diabetes Association (2016) · Diabetes Care · doi:10.2337/dc17-s011 · Cited by 468
From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Gastaldelli, A., & Cusi, K. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.07.002 · Cited by 455
Diverse roles of mitochondria in ischemic stroke
Yang, J., Mukda, S., & Chen, S. (2018) · Redox Biology · doi:10.1016/j.redox.2018.03.002 · Cited by 459
American D iabetes A ssociation S tandards of M edical C are in D iabetes 2017
Marathe, P. H., Gao, H. X., & Close, K. L. (2017) · Journal of Diabetes · doi:10.1111/1753-0407.12524 · Cited by 468
Renoprotective effects of sodium-glucose cotransporter-2 inhibitors
Heerspink, H. J. L., Kosiborod, M., Inzucchi, S. E., & Cherney, D. Z. I. (2018) · Kidney International · doi:10.1016/j.kint.2017.12.027 · Cited by 393
Self-citationThiazolidinediones: the forgotten diabetes medications
Lebovitz, H. E. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1270-y · Cited by 388
Distinct but complementary contributions of PPAR isotypes to energy homeostasis
Dubois, V., Eeckhoute, J., Lefèbvre, P., & Staels, B. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88894 · Cited by 397
Insulin resistance and cardiovascular disease
Kosmas, C. E., Bousvarou, M. D., Kostara, C. E., Papakonstantinou, E. J., Salamou, E., & Guzman, E. (2023) · Journal of International Medical Research · doi:10.1177/03000605231164548 · Cited by 434
Cefalu, W. T., Kaul, S., Gerstein, H. C., Holman, R. R., Zinman, B., Skyler, J. S., Green, J. B., Buse, J. B., Inzucchi, S. E., Leiter, L. A., et al. (2017) · Diabetes Care · doi:10.2337/dci17-0057 · Cited by 387
Self-citationManagement of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action
Bril, F., & Cusi, K. (2017) · Diabetes Care · doi:10.2337/dc16-1787 · Cited by 341
Ueki, K., Sasako, T., Okazaki, Y., Kato, M., Okahata, S., Katsuyama, H., Haraguchi, M., Morita, A., Ohashi, K., Hara, K., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30327-3 · Cited by 313
Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors
Francque, S., Szabo, G., Abdelmalek, M. F., Byrne, C. D., Cusi, K., Dufour, J.-F., Roden, M., Sacks, F., & Tacke, F. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00366-5 · Cited by 316
Arnold, S. V., Bhatt, D. L., Barsness, G. W., Beatty, A. L., Deedwania, P. C., Inzucchi, S. E., Kosiborod, M., Leiter, L. A., Lipska, K. J., Newman, J. D., et al. (2020) · Circulation · doi:10.1161/cir.0000000000000766 · Cited by 304
Self-citationVaccaro, O., Masulli, M., Nicolucci, A., Bonora, E., Del Prato, S., Maggioni, A. P., Rivellese, A. A., Squatrito, S., Giorda, C. B., Sesti, G., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30317-0 · Cited by 292
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S., DeFronzo, R. A., Einhorn, D., Fonseca, V. A., et al. (2019) · Endocrine Practice · doi:10.4158/cs-2018-0535 · Cited by 297
“Cardiovascular benefits, such as reduced major adverse cardiovascular events, have been documented in T2D and in patients with prediabetes and a history of stroke (75,76).”
BackgroundLegchenko, E., Chouvarine, P., Borchert, P., Fernandez‐Gonzalez, A., Snay, E. R., Meier, M., Maegel, L., Mitsialis, S. A., Rog‐Zielinska, E. A., Kourembanas, S., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0303 · Cited by 294
SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study
Abdul‐Ghani, M. A., Prato, S. D., CHILTON, R. J., & DeFronzo, R. A. (2016) · Diabetes Care · doi:10.2337/dc16-0041 · Cited by 303
Prediabetes and Cardiovascular Disease
Brannick, B., & Dagogo-Jack, S. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2017.10.001 · Cited by 293
Treatment of type 2 diabetes: challenges, hopes, and anticipated successes
Nauck, M. A., Wefers, J., & Meier, J. J. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00113-3 · Cited by 315
Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence
Cheng, H. S., Tan, W., Low, Z. S., Marvalim, C., Lee, J. Y. H., & Tan, N. S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205055 · Cited by 282
“III (3876) Reduced risk of stroke and myocardial infarction among non-diabetic patients with high CVD risk [96]”
BackgroundNon-alcoholic fatty liver disease: A patient guideline
Francque, S. M., Marchesini, G., Kautz, A., Walmsley, M., Dorner, R., Lazarus, J. V., Zelber-Sagi, S., Hallsworth, K., Busetto, L., Frühbeck, G., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100322 · Cited by 264
PPAR Agonists and Metabolic Syndrome: An Established Role?
Botta, M., Audano, M., Sahebkar, A., Sirtori, C. R., Mitro, N., & Ruscica, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041197 · Cited by 260
ESVM Guideline on peripheral arterial disease
Frank, U., Nikol, S., Belch, J. J. F., Boc, V., Brodmann, M., Carpentier, P., Chraim, A., Canning, C., Dimakakos, E. P., Gottsäter, A., et al. (2019) · VASA · doi:10.1024/0301-1526/a000834 · Cited by 275
Ryan, D. H., Lingvay, I., Colhoun, H. M., Deanfield, J., Emerson, S. S., Kahn, S. E., Kushner, R. F., Marso, S., Plutzky, J., Brown-Frandsen, K., et al. (2020) · American Heart Journal · doi:10.1016/j.ahj.2020.07.008 · Cited by 249
Diabetes and Stroke: What Are the Connections?
Mosenzon, O., CHENG, A. Y. Y., Rabinstein, A. A., & Sacco, S. (2023) · Journal of Stroke · doi:10.5853/jos.2022.02306 · Cited by 286
Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists
Liu, Q. K. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1431292 · Cited by 265
“Pioglitazone represents another potentially important therapy for preventing stroke events (258).”
BackgroundCalvier, L., Chouvarine, P., Legchenko, E., Hoffmann, N. A., Geldner, J., Borchert, P., Jonigk, D. D., Mozes, M. M., & Hansmann, G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.011 · Cited by 242
Pioglitazone use and risk of bladder cancer: Population based cohort study
Tuccori, M., Filion, K. B., Yin, H., Yu, O. H., Platt, R. W., & Azoulay, L. (2016) · BMJ · doi:10.1136/bmj.i1541 · Cited by 237
Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair
Cai, W., Yang, T., Liu, H., Han, L., Zhang, K., Hu, X., Zhang, X., Yin, K., Gao, Y., Bennett, M. V. L., et al. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.10.002 · Cited by 240
Ma, X., Dong, L., Shao, Q., Cheng, Y., Lv, S., Sun, Y., Shen, H., Wang, Z., Zhou, Y., & Liu, X. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01006-7 · Cited by 235
The Relationship Between Type 2 Diabetes, NAFLD, and Cardiovascular Risk
Caussy, C., Aubin, A., & Loomba, R. S. (2021) · Current Diabetes Reports · doi:10.1007/s11892-021-01383-7 · Cited by 253
Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management
Marjot, T., Moolla, A., Cobbold, J. F., Hodson, L., & Tomlinson, J. W. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz009 · Cited by 228
Dawson, J., Béjot, Y., Christensen, L. M., Marchis, G. M. D., Dichgans, M., Hagberg, G., Heldner, M. R., Milionis, H. J., Li, L., Pezzella, F. R., et al. (2022) · European Stroke Journal · doi:10.1177/23969873221100032 · Cited by 260
Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes
DeFronzo, R. A., Inzucchi, S., Abdul-Ghani, M., & Nissen, S. E. (2019) · Diabetes and Vascular Disease Research · doi:10.1177/1479164118825376 · Cited by 223
Self-citationWein, T. H., Lindsay, M. P., Côté, R., Foley, N. C., Berlingieri, J., Bhogal, S. K., Bourgoin, A., Buck, B. H., Cox, J. L., Davidson, D., et al. (2017) · International Journal of Stroke · doi:10.1177/1747493017743062 · Cited by 227
Mantovani, A., Byrne, C. D., & Targher, G. (2022) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00261-2 · Cited by 230
Cardiovascular disease in diabetes, beyond glucose
Eckel, R. H., Bornfeldt, K., & Goldberg, I. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.001 · Cited by 235
Harrison, S. A., Alkhouri, N., Davison, B. A., Sanyal, A., Edwards, C., Colca, J. R., Lee, B. H., Loomba, R., Cusi, K., Kolterman, O., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.10.023 · Cited by 211
Liao, H.-W., Saver, J. L., Wu, Y.-L., Chen, T.-H., Lee, M., & Ovbiagele, B. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-013927 · Cited by 198
3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2023
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Gaglia, J. L., Hilliard, M. E., Isaacs, D. M., et al. (2022) · Diabetes Care · doi:10.2337/dc23-s003 · Cited by 220
van Baar, M. J. B., van Ruiten, C. C., Muskiet, M. H. A., van Bloemendaal, L., IJzerman, R. G., & van Raalte, D. H. (2018) · Diabetes Care · doi:10.2337/dc18-0588 · Cited by 208
“This result was confirmed by the Insulin Resistance Intervention After Stroke (IRIS) study (87), which demonstrated that in patients who had insulin resistance along with a recent history of ischemic stroke or transient ischemic attack, pioglitazone significantly reduces the event rate of fatal or nonfatal MI and stro…”
ResultBril, F., Kalavalapalli, S., Clark, V. C., Lomonaco, R., Soldevila-Pico, C., Liu, I.-C., Orsak, B., Tio, F., & Cusi, K. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.12.001 · Cited by 199
Liu, L., Li, Z., Zhou, H., Duan, W., Huo, X., Xu, W., Li, S., Nie, X., Liu, H., Liu, J., et al. (2023) · Stroke and Vascular Neurology · doi:10.1136/svn-2023-002998 · Cited by 227
Self-citationSelective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling
Langlet, F., Haeusler, R. A., Lindén, D., Ericson, E., Norris, T., Johansson, A., Cook, J. R., Aizawa, K. S., Wang, L., Buettner, C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.045 · Cited by 201
“Restoring insulin sensitivity is an effective approach to prevent and treat diabetes (Berkowitz et al., 1996) and to reduce its macrovascular complications (Kernan et al., 2016).”
Pharmacotherapy of type 2 diabetes: An update
Upadhyay, J., Pοlyzos, S. A., Perakakis, N., Thakkar, B., Paschou, S. Α., Katsiki, N., UNDERWOOD, P. C., Park, K., Seufert, J., Kang, E. S., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.08.010 · Cited by 196
New Insights Into Cerebrovascular Pathophysiology and Hypertension
Webb, A. J. S., & Werring, D. J. (2022) · Stroke · doi:10.1161/strokeaha.121.035850 · Cited by 210
Machine learning in precision diabetes care and cardiovascular risk prediction
Oikonomou, E. K., & Khera, R. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01985-3 · Cited by 190
Precision medicine in the management of type 2 diabetes
Gloyn, A. L., & Drucker, D. J. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30052-4 · Cited by 201
Management of non-alcoholic fatty liver disease
Petroni, M. L., Brodosi, L., Bugianesi, E., & Marchesini, G. (2021) · BMJ · doi:10.1136/bmj.m4747 · Cited by 193
Diabetes mellitus and stroke: A clinical update
Tun, N. N., Arunagirinathan, G., Munshi, S. K., & Pappachan, J. M. (2017) · World Journal of Diabetes · doi:10.4239/wjd.v8.i6.235 · Cited by 177
Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk
Goldfine, A. B., & Shoelson, S. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88884 · Cited by 176
Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020
Gladstone, D. J., Lindsay, M. P., Douketis, J., Smith, E. E., Dowlatshahi, D., Wein, T., Bourgoin, A., Cox, J., Falconer, J. B., Graham, B. R., et al. (2022) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2021.127 · Cited by 168
RSSDI-ESI clinical practice recommendations for the management of type 2 diabetes mellitus 2020
Madhu, S., Chawla, R., Makkar, B. M., Ghosh, S. K., Saboo, B., & Kalra, S. (2020) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_225_20 · Cited by 182
NAFLD, and cardiovascular and cardiac diseases: Factors influencing risk, prediction and treatment
Targher, G., Corey, K. E., & Byrne, C. D. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2020.101215 · Cited by 174
Triglyceride Glucose Index and Prognosis of Patients With Ischemic Stroke
Zhou, Y., Pan, Y., Yan, H., Wang, Y., Li, Z., Zhao, X., Li, H., Meng, X., Wang, C., Liu, L., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00456 · Cited by 160
Iron, ferroptosis, and ischemic stroke
Guo, J., Tuo, Q., & Lei, P. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15807 · Cited by 163
Ghosh-Swaby, O. R., Goodman, S. G., Leiter, L. A., Cheng, A., Connelly, K. A., Fitchett, D., Jüni, P., Farkouh, M. E., & Udell, J. A. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30038-3 · Cited by 159
Insulin resistance in type 2 diabetes mellitus
Accili, D., Deng, Z., & Liu, Q. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01114-y · Cited by 219
Non-alcoholic fatty liver disease and cardiovascular disease: assessing the evidence for causality
Brouwers, M. C. G. J., Simons, N., Stehouwer, C. D. A., & Isaacs, A. J. (2019) · Diabetologia · doi:10.1007/s00125-019-05024-3 · Cited by 154
Pioglitazone and bladder cancer risk: a systematic review and meta‐analysis
Tang, H., Shi, W., Fu, S., Wang, T., Zhai, S., Song, Y., & Han, J. (2018) · Cancer Medicine · doi:10.1002/cam4.1354 · Cited by 162
Interventions for improving modifiable risk factor control in the secondary prevention of stroke
Bridgwood, B. M., Lager, K. E., Mistri, A. K., Khunti, K., Wilson, A., & Modi, P. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009103.pub3 · Cited by 156
Strategies for Achieving Healthy Vascular Aging
Nowak, K. L., Rossman, M. J., Chonchol, M., & Seals, D. R. (2018) · Hypertension · doi:10.1161/hypertensionaha.117.10439 · Cited by 155
Pharmacotherapy of type 2 diabetes: An update and future directions
DeMarsilis, A. J., Reddy, N., Boutari, C., Filippaios, A., Sternthal, E., Katsiki, N., & Mantzoros, C. S. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155332 · Cited by 173
Pioglitazone for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis
Lee, M., Saver, J. L., Liao, H.-W., Lin, C.-H., & Ovbiagele, B. (2017) · Stroke · doi:10.1161/strokeaha.116.013977 · Cited by 147
The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial
Gerstein, H. C., Hart, R., Colhoun, H. M., Diaz, R., Lakshmanan, M., Botros, F. T., Probstfield, J., Riddle, M. C., Rydén, L., Atisso, C. M., et al. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30423-1 · Cited by 137
Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived?
Abdul-Ghani, M. A., DeFronzo, R. A., Prato, S. D., CHILTON, R. J., Singh, R., & Ryder, R. E. J. (2017) · Diabetes Care · doi:10.2337/dc16-2736 · Cited by 146
Diagnosis and Treatment of Type 2 Diabetes in Adults
Kalyani, R. R., Neumiller, J. J., Maruthur, N. M., & Wexler, D. J. (2025) · JAMA · doi:10.1001/jama.2025.5956 · Cited by 145
Mansi, I. A., Chansard, M., Lingvay, I., Zhang, S., Halm, E. A., & Alvarez, C. A. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.5714 · Cited by 144
Metadata
- Authors
- Kernan, W. N., Viscoli, C. M., Furie, K. L., Young, L. H., Inzucchi, S. E., Gorman, M., Guarino, P. D., Lovejoy, A. M., Peduzzi, P. N., Conwit, R., Brass, L. M., Schwartz, G. G., Adams, H. P., Berger, L., Carolei, A., Clark, W., Coull, B., Ford, G. A., Kleindorfer, D., O’Leary, J. R., Parsons, M. W., Ringleb, P., Sen, S., Spence, J. D., Tanne, D., Wang, D., & Winder, T. R.
- Affiliations
- Western University (CA)
- University of Vermont (US)
- Yale University (US)
- ORCID
- Kernan, Walter N.
- Furie, Karen L.
- Young, Lawrence H.
- Inzucchi, Silvio E.
- Gorman, Mark
- Guarino, Peter D.
- Peduzzi, Peter N.
- Conwit, Robin
- Schwartz, Gregory G.
- Adams, Harold P.
- Carolei, Antonio
- Clark, Wayne
- Coull, Bruce
- Ford, Gary A.
- Kleindorfer, Dawn
- Parsons, Mark W.
- Ringleb, Peter
- Sen, Souvik
- Spence, J. David
- Wang, David
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-04-07
- Volume
- 374
- Issue
- 14
- Pages
- 1321-1331
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4887756
- OpenAlex
- W2274836352
- Semantic Scholar
- 192abcbc3012aaf42b8606eddd5adedcee96ce93
- Cited by
- 1,124
- References
- 63
- Citations by year
- 2026: 57 · 2025: 67 · 2024: 93 · 2023: 104 · 2022: 83 · 2021: 131 · 2020: 116 · 2019: 114 · 2018: 120 · 2017: 150 · 2016: 86
- FWCI
- 104.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Yale University
- National Institute for Health and Care Research (NF-SI-0512-10089)
- National Institutes of Health (UL1TR001863)
- National Cancer Institute (P30CA016359)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK045735)
- National Institute of Neurological Disorders and Stroke (U01NS044876)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- pioglitazone, ischemic stroke, transient ischemic attack, insulin resistance, HOMA-IR, secondary stroke prevention, myocardial infarction, weight gain, edema, bone fractures, adverse drug reactions, thiazolidinediones, cardiovascular risk factors, all-cause mortality, stroke recurrence, myocardial infarction recurrence
- MeSH terms
- Pioglitazone, Aged, Brain Ischemia, Ischemic Attack, Transient, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Middle Aged, Myocardial Infarction, Weight Gain, Stroke, Thiazolidinediones, Peroxisome Proliferator-Activated Receptors, Fractures, Bone, Secondary Prevention
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
