The DOI matches its Crossref record; 18 of the 20 references it cites were found in a registry or an index; 7 of the 29 sources its claims cite were checked for support.
Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes
Open accessAbstract
Importance: The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described. Objective: To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control. Design, Setting, and Participants: Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020; follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin. Interventions: Patients were randomized in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks. Tirzepatide was initiated at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved. Main Outcomes and Measures: The primary end point was mean change from baseline in glycated hemoglobin A1c (HbA1c) at week 40. The 5 key secondary end points included mean change in body weight and percentage of patients achieving prespecified HbA1c levels. Results: Among 475 randomized participants (211 [44%] women; mean [SD] age, 60.6 [9.9] years; mean [SD] HbA1c, 8.31% [0.85%]), 451 (94.9%) completed the trial. Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group. At week 40, mean HbA1c change from baseline was -2.40% with 10-mg tirzepatide and -2.34% with 15-mg tirzepatide vs -0.86% with placebo (10 mg: difference vs placebo, -1.53% [97.5% CI, -1.80% to -1.27%]; 15 mg: difference vs placebo, -1.47% [97.5% CI, -1.75% to -1.20%]; P < .001 for both). Mean HbA1c change from baseline was -2.11% with 5-mg tirzepatide (difference vs placebo, -1.24% [95% CI, -1.48% to -1.01%]; P < .001]). Mean body weight change from baseline was -5.4 kg with 5-mg tirzepatide, -7.5 kg with 10-mg tirzepatide, -8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo (5 mg: difference, -7.1 kg [95% CI, -8.7 to -5.4]; 10 mg: difference, -9.1 kg [95% CI, -10.7 to -7.5]; 15 mg: difference, -10.5 kg [95% CI, -12.1 to -8.8]; P < .001 for all). Higher percentages of patients treated with tirzepatide vs those treated with placebo had HbA1c less than 7% (85%-90% vs 34%; P < .001 for all). The most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%). Conclusions and Relevance: Among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine, the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04039503.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
50 Own result · 12 Own method · 7 No full text of the sources · 4 Partly supported · 3 Own interpretation · 2 Supported so far · 2 Sources not found · 1 No basis given · accuracy not yet measured
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
“At week 40, the mean body weight change from baseline was -5.4 kg with 5-mg tirzepatide, -7.5 kg with 10-mg tirzepatide, and -8.8 kg with 15-mg tirzepatide vs 1.6 kg with placebo (5 mg: difference, -7.1 kg [95% CI, -8.7 to -5.4]; 10 mg: difference, -9.1 kg [95% CI, -10.7 to -7.5]; 15 mg: difference, -10.5 kg [95% CI, -12.1 to -8.8]; P < .001for all; treatment-regimen estimand; Table 2; eFigure 3A”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Key Secondary Outcomes
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.
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
“At week 40, tirzepatide significantly reduced mean fasting serum glucose by -58.2 mg/dL for the 5-mg dose, -64.0 mg/dL for the 10-mg dose, and -62.6 mg/dL for the 15-mg dose, compared with -39.2 mg/dL for placebo (5 mg: difference, -19.0 mg/dL [95% CI, -26.6 to -11.4]; P < .001; 10 mg: difference, -24.9 mg/dL [95% CI, -32.3 to -17.4]; P < .001;15 mg: difference, -23.4 mg/dL [95% CI, -31.0 to -15.8”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Key Secondary 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
“At week 40, tirzepatide significantly reduced mean fasting serum glucose by -58.2 mg/dL for the 5-mg dose, -64.0 mg/dL for the 10-mg dose, and -62.6 mg/dL for the 15-mg dose, compared with -39.2 mg/dL for placebo (5 mg: difference, -19.0 mg/dL [95% CI, -26.6 to -11.4]; P < .001; 10 mg: difference, -24.9 mg/dL [95% CI, -32.3 to -17.4]; P < .001;15 mg: difference, -23.4 mg/dL [95% CI, -31.0 to -15.8”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Key Secondary 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
“At week 40, the mean percent change from baseline in insulin dose was 13.0% for 5-mg tirzepatide, 8.1% for 10-mg tirzepatide, -11.4% for 15-mg tirzepatide, and 75.0% for placebo (5 mg: difference, -35.4% [95% CI, -46.0% to -22.8%]; 10 mg: difference, -38.2% [95% CI, -48.3% to -26.1%]; 15 mg: difference, -49.3% [95% CI, -57.7% to -39.4%]; P < .001for all; Table 2; Figure 2F; eFigure 4 in Supplement”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Additional Secondary and Exploratory End Points
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
“Similarly, a signifi- cantly greater percentage of patients receiving tirzepatide vs placebo achieved the 2 composite outcomes, HbA 1c less than 7.0% (78%-80% vs 12%) or less than or equal to 6.5% (67%- 78% vs 8%) without body weight gain and without clinically significant documented hypoglycemia or severe hypoglyce- mia (P < .001 for all; efficacy estimand; eTable 2 in Supple- ment 2).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Additional Secondary and Exploratory End Points
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
“At week 40, the mean body weight change from baseline was -5.4 kg with 5-mg tirzepatide, -7.5 kg with 10-mg tirzepatide, and -8.8 kg with 15-mg tirzepatide vs 1.6 kg with placebo (5 mg: difference, -7.1 kg [95% CI, -8.7 to -5.4]; 10 mg: difference, -9.1 kg [95% CI, -10.7 to -7.5]; 15 mg: difference, -10.5 kg [95% CI, -12.1 to -8.8]; P < .001for all; treatment-regimen estimand; Table 2; eFigure 3A”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Key Secondary Outcomes
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.
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
“Similarly, more patients receiving 10-mg and 15-mg tirzepatide met the HbA 1c target of less than 5.7% vs placebo at week 40 (42% and 50% vs 3%; P < .001for all; treatmentregimen estimand; Table 2, Figure 2C).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Key Secondary 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
“Patients receiving tirzepatide, compared with placebo, were more likely to achieve body weight loss of 5% (48%-72% vs 6%), 10% (21%-42% vs 1%), and 15% (7%-24% vs 0%) (P < .05for all; treatment-regimen estimand; Table 2; eFigure 3B in Supplement 2).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Additional Secondary and Exploratory End Points
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.
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 most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Abstract
plainn = 475- 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
“Similarly, a signifi- cantly greater percentage of patients receiving tirzepatide vs placebo achieved the 2 composite outcomes, HbA 1c less than 7.0% (78%-80% vs 12%) or less than or equal to 6.5% (67%- 78% vs 8%) without body weight gain and without clinically significant documented hypoglycemia or severe hypoglyce- mia (P < .001 for all; efficacy estimand; eTable 2 in Supple- ment 2).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Additional Secondary and Exploratory End Points
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.
- It may state two separate claims as one. 20
- Probably not a substantial claim. 18
- 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
“Although increasing the basal insulin dose often improves glycemic control, it can also be associated with increased risk of hypoglycemia and weight gain, resulting in inadequate intensification of insulin dose in clinical practice.1”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Partly supportedcites [1] Swinnen, 2009, Insulin therapy for type 2 diabetes., Diabetes Care sourceExperimental — accuracy not yet measured
The 'Titration and timing of basal insulin' section says dose titration can achieve glycemic targets, and 'When should insulin therapy be intensified?' says hypoglycemia can limit aggressive titration. The 'Weight gain' section associates insulin therapy with weight gain but finds no evidence of a dose–response relationship in studies of basal insulin initiation. The paper also notes prolonged uncontrolled hyperglycemia in practice, but does not establish that weight gain causes inadequate basal-dose intensification. (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.
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
“It also suppresses glucagon secretion during hyperglycemia, signals glucagon secretion during hypoglycemia, facilitates postprandial lipid clearance, and promotes satiety.[8][9][10]”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Partly supportedcites [8] Baggio, 2021, Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease., Mol Metab sourceExperimental — accuracy not yet measured
The GIP section (page not specified) says GIP promotes lipid accretion in fat cells, supporting a related role in lipid handling. It does not state that GIP facilitates clearance of circulating lipids after a meal; searches for postprandial lipid clearance and meal-related triglyceride clearance did not establish that more specific claim. (LLM, conf=0.75)
- Not checked — no full text of the sourcecites [9] Campbell, 2013, Pharmacology, physiology, and mechanisms of incretin hormone action., Cell Metab source
- Not checked — no full text of the sourcecites [10] Nauck, 2018, Incretin hormones: their role in health and disease., Diabetes Obes Metab 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.
- 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 also suppresses glucagon secretion during hyperglycemia, signals glucagon secretion during hypoglycemia, facilitates postprandial lipid clearance, and promotes satiety.[8][9][10]”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Supportedcites [8] Baggio, 2021, Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease., Mol Metab source
The Glucose-dependent insulinotropic polypeptide (GIP) section states that GIP modestly increases glucagon secretion during hypoglycemia, directly supporting the attributed claim. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [9] Campbell, 2013, Pharmacology, physiology, and mechanisms of incretin hormone action., Cell Metab source
- Not checked — no full text of the sourcecites [10] Nauck, 2018, Incretin hormones: their role in health and disease., Diabetes Obes Metab 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When added to basal insulin, selective glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated improved glycemic control and body weight loss without increasing the risk of hypoglycemia and reducing insulin requirements.[2][3][4][5][6]”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Not checked — no full text of the sourcecites [2] Pozzilli, 2017, Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD-9)., Diabetes Obes Metab source
- Partly supportedcites [3] Zinman, 2019, Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: the PIONEER 8 trial., Diabetes Care sourceExperimental — accuracy not yet measured
The Introduction says GLP-1 receptor agonists added to insulin reduce HbA1c and body weight without increasing hypoglycemia, and the Conclusions report an insulin-sparing effect with oral semaglutide 7 and 14 mg. But PIONEER 8 studied basal, basal-bolus, and premixed insulin regimens; its reported reduction in total daily insulin dosage is not established specifically for the basal-insulin group. (LLM, conf=0.83)
- Supportedcites [4] Rosenstock, 2020, Impact of a weekly glucagon-like peptide 1 receptor agonist, albiglutide, on glycemic control and on reducing prandial insulin use in type 2 diabetes inadequately controlled on multiple insulin therapy: a randomized trial., Diabetes Care source
The Conclusions report that adding weekly albiglutide while stopping prandial insulin improved glucose control, reduced body weight and total insulin dose, and caused less hypoglycemia; basal insulin requirements were unchanged. The Introduction also describes favorable glycemic, weight, and hypoglycemia outcomes for GLP-1 receptor agonists used with basal insulin. (LLM, conf=0.91)
boosteddirect- 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.
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 also suppresses glucagon secretion during hyperglycemia, signals glucagon secretion during hypoglycemia, facilitates postprandial lipid clearance, and promotes satiety.[8][9][10]”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Supportedcites [8] Baggio, 2021, Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease., Mol Metab source
The Glucose-dependent insulinotropic polypeptide (GIP) section explicitly states that GIP suppresses glucagon levels during hyperglycemia. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites [9] Campbell, 2013, Pharmacology, physiology, and mechanisms of incretin hormone action., Cell Metab source
- Not checked — no full text of the sourcecites [10] Nauck, 2018, Incretin hormones: their role in health and disease., Diabetes Obes Metab 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It also suppresses glucagon secretion during hyperglycemia, signals glucagon secretion during hypoglycemia, facilitates postprandial lipid clearance, and promotes satiety.[8][9][10]”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Partly supportedcites [8] Baggio, 2021, Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease., Mol Metab sourceExperimental — accuracy not yet measured
The GIP section reports that activating hypothalamic GIP-receptor-expressing neurons may reduce food intake, consistent with findings from GIP-receptor agonists in mice with diet-induced obesity. This supports a possible appetite-related effect, but the paper does not establish the unqualified claim that GIP itself promotes satiety. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [9] Campbell, 2013, Pharmacology, physiology, and mechanisms of incretin hormone action., Cell Metab source
- Not checked — no full text of the sourcecites [10] Nauck, 2018, Incretin hormones: their role in health and disease., Diabetes Obes Metab 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.
- 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
“Mean HbA 1c change from baseline was -2.11% with 5-mg tirzepatide (difference vs placebo, -1.24% [95% CI, -1.48% to -1.01%]; P < .001]).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Abstract
plaindirectn = 475 ·- 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 quote only partly states this claim.
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
“At week 40, mean HbA 1c change from baseline was -2.40% with 10-mg tirzepatide and -2.34% with 15-mg tirzepatide vs -0.86% with placebo (10 mg: difference vs placebo, -1.53% [97.5% CI, -1.80% to -1.27%]; 15 mg: difference vs placebo, -1.47% [97.5% CI, -1.75% to -1.20%]; P < .001for both).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Abstract
plaindirectn = 475- 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
“Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Abstract
plainn = 475- 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
“No deaths occurred during the study.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Adverse Events and Tolerability
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 most fre-quent treatment-emergent adverse event in the tirzepatide groups were gastrointestinal, including diarrhea (12%-21% vs 10% in the placebo group), nausea (13%-18% vs 2.5% in the placebo group), vomiting (7%-13% vs 2.5% in the placebo group), and decreased appetite (7%-14% vs 1.7% in the placebo group) (Table 3).”
- Also stated in: § Discussion · plain
“The most commonly reported treatment-emergent adverse events for patients receiving tirzepatide were gastrointestinal in nature and decreased over time, especially after reaching maintenance doses.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Adverse Events and Tolerability
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.
- Also stated in: § Discussion · 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
“At week 40, mean change in systolic and diastolic blood pressure was -6.1 to -12.6 mm Hg and -2.0 to -4.5 mm Hg for tirzepatide”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Additional Secondary and Exploratory End Points
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 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
“Rates of premature treatment discontinuation due to adverse events were 6.0% (7/116) in the 5-mg tirzepatide group, 8.4% (10/119) in the 10-mg tirzepatide group, 10.8% (13/120) in the 15-mg tirzepatide group, and 2.5% (3/120) in the placebo group (Table 3).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Downloaded From: https://jamanetwork.com/ on 07/10/2023
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
“-1.7 mm Hg and -2.1 mm Hg for the placebo group (eTable 7 in Supplement 2).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Additional Secondary and Exploratory End Points
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
“Investigators, site staff, clinical monitors, external independent adjudication committee members, sponsors, and patients remained blinded to the treatment assignments until study completion.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Randomization and Blinding
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
“Patients were randomized in a 1:1:1:1 ratio to receive 5 mg, 10 mg, or 15 mg of tirzepatide or volume-matched placebo (Figure 1) with a blocking schema (block size of 4) by a computer-generated random sequence using an interactive web response system and stratified based on country, baseline HbA 1c (≤8.0% or >8.0%[≤64 mmol/mol or >64 mmol/mol]), and baseline metformin use.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Randomization and Blinding
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.
In the paper
“Glucose-dependent insulinotropic polypeptide is the primary incretin hormone responsible for mealstimulated insulin secretion in healthy individuals.7”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Not checked — no full text of the sourcecites [7] Gasbjerg, 2019, Separate and combined glucometabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 in healthy individuals., Diabetes 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.
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 cases of suspected pancreatitis and major adverse cardiovascular events were adjudicated by an independent clinical end point committee in a blinded manner (eAppendix in Supplement 2).”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Randomization and Blinding
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 primary objective tested the 10-mg and 15-mg tirzepatide doses in parallel, controlled for multiplicity, and were accompanied by 2-sided 97.5% CIs; statistical significance was defined as P < .025.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Statistical Analyses
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.
In the paper
“Tirzepatide is a novel, once-weekly dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist that is administered via subcutaneous injection and has shown statistically significant reductions in hemoglobin A 1c (HbA 1c ) and body weight compared with the GLP-1 receptor agonist semaglutide (1 mg), 11 insulin degludec, 12 and insulin glargine 13 when added to oral glucose-lower”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Not checked — no full text of the sourcecites [13] Del Prato, 2021, Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial., Lancet 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.
In the paper
“Although treatment guidelines generally recommend using GLP-1 receptor agonists prior to basal insulin in most cases, the treatment sequence may vary because the latter is still widely used as the first injectable therapy in clinical practice due to cost, reimbursement issues, and prescribing habits.16”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Discussion
What the sources say
- Not checked — no full text of the sourcecites [16] Yu, 2017, Characteristics associated with the choice of first injectable therapy among US patients with type 2 diabetes., Clin Ther source
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. 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
“Sixth, due to the global nature of the study and the countries participating in it, the percentage of participants identifying as certain racial or ethnic groups was low.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Limitations
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.
In the paper
“Tirzepatide is a novel, once-weekly dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist that is administered via subcutaneous injection and has shown statistically significant reductions in hemoglobin A 1c (HbA 1c ) and body weight compared with the GLP-1 receptor agonist semaglutide (1 mg), 11 insulin degludec, 12 and insulin glargine 13 when added to oral glucose-lower”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Not checked — no full text of the sourcecites [12] Ludvik, 2021, Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial., Lancet source
boosteddirect- 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
“Tirzepatide is a novel, once-weekly dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist that is administered via subcutaneous injection and has shown statistically significant reductions in hemoglobin A 1c (HbA 1c ) and body weight compared with the GLP-1 receptor agonist semaglutide (1 mg), 11 insulin degludec, 12 and insulin glargine 13 when added to oral glucose-lower”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Not checked — no full text of the sourcecites [11] Frías, 2021, Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes., N Engl J Med source
boosteddirect- 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
“Second, the lack of adjustment of insulin dose for the first 4 weeks of treatment may have initially favored patients receiving tirzepatide, although this was compensated during the remainder of the 40-week treatment period.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Limitations
hedgedconditional- 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
“First, the patients enrolled in this study were treated with insulin glargine with or without metformin, and therefore the observations may not be directly extrapolated to other regimens using different oral antihyperglycemic medications.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Limitations
hedgedconditional- 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.
In the paper
“The effects of tirzepatide on glycemic control, body weight, lipid levels, and blood pressure on a background of titrated basal insulin in this trial were consistent with previously reported studies of tirzepatide [11][12][13][14] and further validate its effectiveness across different patient populations differing in the duration of the disease, background glucose-lowering therapies, or comorbidi”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Discussion
What the sources say
- Not matchedcites [11][12][13][14]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- 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
“Strengths of the study include the randomized, doubleblind, placebo-controlled design and titration of background basal insulin using a treat-to-target algorithm.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > 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.
Probably not a substantial claim. 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
“Additionally, tirzepatide was associated with reductions in blood pressure and improvements in lipid profile.[11][12][13][14]”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
What the sources say
- Not checked — no full text of the sourcecites [11] Frías, 2021, Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes., N Engl J Med source
- Not checked — no full text of the sourcecites [12] Ludvik, 2021, Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial., Lancet source
- Not checked — no full text of the sourcecites [13] Del Prato, 2021, Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial., Lancet source
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.
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
“Tirzepatide is a novel, once-weekly dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist that is administered via subcutaneous injection and has shown statistically significant reductions in hemoglobin A 1c (HbA 1c ) and body weight compared with the GLP-1 receptor agonist semaglutide (1 mg), 11 insulin degludec, 12 and insulin glargine 13 when added to oral glucose-lower”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > B
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
“Fourth, although gastrointestinal adverse events and their severity are typically self-reported in most clinical trials, this approach has limitations.”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Limitations
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper relies on this without support.
This is the first trial to assess the efficacy and adverse event profile of a dual GIP/GLP-1 receptor agonist in combination with a basal insulin regimen.
“To the authors' knowledge, this is the first trial to assess the efficacy and adverse event profile of a dual glucosedependent insulinotropic polypeptide/GLP-1 receptor agonist in combination with a basal insulin regimen.”
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
“In a back-to-back published Phase 2 study comprising of subjects with obesity and T2D, 36 weeks of retatrutide treatment reduced body weight by ~16.9%, compared to ~2% or ~3% with dulaglutide or placebo, respectively;”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [166]
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
“furthermore, the triagonist lowered HbA1c levels by ~2%, compared to ~1.4% or ~0.01% with dulaglutide or placebo, respectively, at the 24 week time point166.”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [166]
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
“In individuals who are intensified to insulin therapy, combination therapy with a GLP-1 RA or a dual GIP and GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effects, as well as weight and hypoglycemia benefits, than treatment intensification with insulin alone (89,131).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [131]
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
“Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone (SURPASS) studies have shown that tirzepatide reduced HbA1c and fasting glucose levels more than the titrated insulin degludec, insulin glargine or 1 mg once a week semaglutide independently of the baseline levels of HbA1c.”
From The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update. (2024) · cites this paper as [55]
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, about 11% of those with T2DM did not respond even to the highest dose of tirzepatide [53-55].”
From The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update. (2024) · cites this paper as [55]
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
“In summary, dual and triple agonists related to GLP-1 represent significant advances in the field of diabetes treatment,167,168 demonstrating the future trend of enhancing therapeutic effects by targeting multiple biomarkers.136,169,170”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [167]
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
“In the SURPASS trials, tirzepatide consistently outperformed placebo and active comparators in reducing HbA1c across all doses [90, 93–96].”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [93]
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, these GI AEs were mostly mild to moderate in severity, temporary, and tolerable. They typically occurred at treatment initiation or during dose-escalation phases, and gradually diminished over time, rarely leading to treatment discontinuation [12, 18–20].”
From Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial (2024) · cites this paper as [19]
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
“Mean WL ranged from −11.7 kg to −12.9 kg with tirzepatide 15 mg at 52 weeks and up to 43% of people with T2D achieved ≥ 15% WL, even if tirzepatide was not combined with a lifestyle intervention at SURPASS programme.”
From Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? (2024) · cites this paper as [43]
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 health benefits seen with continued treatment with the maximum tolerated dose of tirzepatide during this study were achieved with a safety profile consistent with that previously reported in SURMOUNT and SURPASS trials and in studies of incretin-based therapies approved for the treatment of obesity and overweight.18,25,26,27,28,29,30,31,32”
From Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (2024) · cites this paper as [29]
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
“In the SURPASS phase 3 trials, tirzepatide (5, 10, and 15 mg) reduced glycated hemoglobin A1c (HbA1c) up to 2.6% and reduced body weight up to 12.9 kg, significantly more than placebo (SURPASS-1), semaglutide 1 mg (SURPASS-2), insulin degludec (SURPASS-3), insulin glargine (SURPASS-4), and placebo as an add on to insulin glargine (SURPASS-5) (5-9).”
From Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2) (2024) · cites this paper as [9]
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
“In the SURPASS phase 3 trials, tirzepatide (5, 10, and 15 mg) reduced glycated hemoglobin A1c (HbA1c) up to 2.6% and reduced body weight up to 12.9 kg, significantly more than placebo (SURPASS-1), semaglutide 1 mg (SURPASS-2), insulin degludec (SURPASS-3), insulin glargine (SURPASS-4), and placebo as an add on to insulin glargine (SURPASS-5) (5-9).”
From Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2) (2024) · cites this paper as [9]
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
“to lower the risks of hypoglycemia and weight gain associated with insulin therapy (131,172).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [131]
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
“In individuals who are intensified to insulin therapy, combination therapy with a GLP-1 RA or a dual GIP and GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effects, as well as weight and hypoglycemia benefits, than treatment intensification with insulin alone (89,131).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [131]
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
“In phase 3 trials in patients with T2D, tirzepatide reduced glycated hemoglobin by 20.8 to 28.4 mmol/mol (1.9% to 2.6%) and reduced body weight by 5.6% to 13.9% (8-12).”
From Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test (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
“Clinical trials have shown that tirzepatide leads to incremental benefits with respect to glycemic control, weight, atherogenic lipoprotein levels, blood pressure, and kidney-related outcomes as compared with selective GLP-1 receptor agonists or other glucose-lowering agents.[16][17][18][19][20][21][22]”
From Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (2025) · cites this paper as [21]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In the Phase III clinical trial program, tirzepatide demonstrated superior glycemic ef fi cacy to placebo (183,184), subcutaneous semaglutide 1.0 mg weekly (185), insulin degludec (186), and insulin glargine (187).”
The cited source says what the claim attributes to it.
In the citing paper
“Seven studies [11, 12, 16–20] ultimately met all selection criteria and were included in the meta-analysis.”
The cited source says what the claim attributes to it.
In the citing paper
“These preclinical findings are consistent with the results of multiple RCTs [11, 12, 16–20] that evaluated the impact of tirzepatide on weight loss, and further supported by the results of our meta-analysis.”
The cited source says what the claim attributes to it.
In the citing paper
“The evaluation of the remaining four studies [12, 18–20] found them to have low risk in all five domains, indicating an overall low risk of bias for each individual study.”
The cited source says what the claim attributes to it.
In the citing paper
“Compared to an HbA 1c reduction of -0.86% in the placebo group, the 10-mg group had an HbA 1c reduction of -2.40% (-1.53% difference; 97.5% CI, -1.80% to -1.27%), and the 15-mg group had a reduction of -2.34% (-1.47% difference; 97.5% CI, -1.75% to -1.20%).25”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [25]
The cited source says what the claim attributes to it.
In the citing paper
“In individuals who are intensified to insulin therapy, combination therapy with a GLP-1 RA or a dual GIP and GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effects, as well as weight and hypoglycemia benefits, than treatment intensification with insulin alone (89,131).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [131]
In the citing paper
“Reduced body weight 5.4–8.8 kg compared to increase of 1.6 kg with placebo”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [196]
In the citing paper
“SURPASS 5: Tirzepatide versus placebo added to titrated insulin glargine improved glycemic control among patients with type 2 diabetes.”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [196]
In the citing paper
“The efficacy of tirzepatide (5, 10 and 15 mg once weekly subcutaneous injection: Mounjaro ) was assessed in the SURPASS trial programme which showed greater glucose-lowering and weight-lowering effects than semaglutide and other GLP-1RAs [57-62].”
From Recent advances in peptide-based therapies for obesity and type 2 diabetes (2024) · cites this paper as [61]
In the citing paper
“Tirzepatide-based evidence from the SURPASS (Researching Tirzepatide in Patients with Type 2 Diabetes for Glycemic Control and Weight Management) trials (SURPASS-1 NCT03954834 and SURPASS-5 NCT04039503) demonstrated dose-dependent, significant weight loss over 40 weeks compared with placebo, along with reductions in BMI and waist circumference [62, 63].”
From GLP-1 Receptor Agonists for Obesity Management in Older Adults: A Scoping Review on the Risk of Sarcopenia and Sarcopenic Obesity (2026) · cites this paper as [62]
In the citing paper
“In the SURPASS trials, the predominant side effects of tirzepatide were gastrointestinal, similar to the safety profiles reported with GLP-1R monoagonists.123,[125][126][127]”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [123]
In the citing paper
“Tirzepatide, a unimolecular dual agonist of GLP-1 and GIP receptors, has been approved for T2D management at the doses of 5, 10 and 15 mg once-weekly based on findings from the phase 3 SURPASS program [40–45].”
In the citing paper
“In these clinical trials, tirzepatide resulted in HbA1c reduction up to 2.6%, with 70–94% of participants achieving HbA1c ≤ 6.5% with tirzepatide 15 mg (Table 2, Figure 3).”
In the citing paper
“Mean WL ranged from −11.7 kg to −12.9 kg with tirzepatide 15 mg at 52 weeks and up to 43% of people with T2D achieved ≥ 15% WL, even if tirzepatide was not combined with a lifestyle intervention at SURPASS programme.”
In the citing paper
“In these clinical trials, tirzepatide resulted in HbA1c reduction up to 2.6%, with 70–94% of participants achieving HbA1c ≤ 6.5% with tirzepatide 15 mg (Table 2, Figure 3).”
In the citing paper
“Glucagon, is a 29‐amino acid peptide hormone produced by the pancreatic α-cells, and its role in increasing hepatic glucose production through glycogenolysis and gluconeogenesis is well described (43).”
In the citing paper
“Glucagon, is a 29‐amino acid peptide hormone produced by the pancreatic α-cells, and its role in increasing hepatic glucose production through glycogenolysis and gluconeogenesis is well described (43).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“| Severe hypoglycemia d | 0 | 2 (1.6) | 1 (0.8) | 0 |”
§ Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial > Conclusions
Reported 1.6 · recomputed 1.680672
Citations
Cites
Correspondence - Tranexamic acid for traumatic brain injury
(2005) · London School of Economics and Political Science Theses Online (London School of Economics and Political Science) · doi:10.1016/s0140-6736 · Cited by 11,894
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
Frías, J. P., Davies, M. J., Rosenstock, J., Pérez Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., Cui, X., & Brown, K. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107519 · Cited by 2,096
Pharmacology, physiology, and mechanisms of incretin hormone action.
Campbell, J. E., & Drucker, D. J. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.008 · Cited by 1,500
Rosenstock, J., Wysham, C., Frías, J. P., Kaneko, S., Lee, C. J., Fernández Landó, L., Mao, H., Cui, X., Karanikas, C. A., & Thieu, V. T. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01324-6 · Cited by 1,080
Incretin hormones: Their role in health and disease
Nauck, M. A., & Meier, J. J. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13129 · Cited by 950
Frias, J. P., Nauck, M. A., Van, J., Kutner, M. E., Cui, X., Benson, C., Urva, S., Gimeno, R. E., Milicevic, Z., Robins, D., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32260-8 · Cited by 815 · cited 1×
“Blood pressure, mean (SD), mm Hg Systolic 137 (16) 138 (15) 137 (16) 140 (15)”
Del Prato, S., Kahn, S. E., Pavo, I., Weerakkody, G. J., Yang, Z., Doupis, J., Aizenberg, D., Wynne, A. G., Riesmeyer, J. S., Heine, R. J., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)02188-7 · Cited by 684
Ludvik, B., Giorgino, F., Jódar, E., Frias, J. P., Fernández Landó, L., Brown, K., Bray, R., & Rodríguez, Á. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01443-4 · Cited by 639
Self-citationSemaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial.
Rodbard, H. W., Lingvay, I., Reed, J., de la Rosa, R., Rose, L., Sugimoto, D., Araki, E., Chu, P.-L., Wijayasinghe, N., & Norwood, P. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00070 · Cited by 412
Self-citationZinman, B., Aroda, V. R., Buse, J. B., Cariou, B., Harris, S. B., Hoff, S. T., Pedersen, K. B., Tarp-Johansen, M. J., Araki, E., PIONEER 8 Investigators, et al. (2019) · Diabetes Care · doi:10.2337/dc19-0898 · Cited by 300
Self-citation
Cited by
Sorted by citations
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206038 · Cited by 3,838
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
“In the Phase III clinical trial program, tirzepatide demonstrated superior glycemic efficacy to placebo (183,184), subcutaneous semaglutide 1.”
BackgroundAhmad, E., Lim, S., Lamptey, R., Webb, D. R., & Davies, M. J. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01655-5 · Cited by 1,120
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
“In the Phase III clinical trial programme, tirzepatide demonstrated superior glycaemic efficacy to placebo [183, 184], subcutaneous semaglutide 1.”
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
Zheng, Z., Zong, Y., Ma, Y., Tian, Y., Pang, Y., Zhang, C., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01931-z · Cited by 1,036
Metadata
- Authors
- Dahl, D., Onishi, Y., Norwood, P., Huh, R., Bray, R., Patel, H., & Rodríguez, Á.
- Affiliations
- Gemeinschaftspraxis für Innere Medizin und Diabetologie, Hamburg, Germany
- The Institute of Medical Science, Asahi Life Foundation (JP)
- Valley Endocrine and Research, Fresno, California
- Eli Lilly (United States) (US)
- Lilly Spain, Alcobendas, Madrid, Spain
- Corresponding author
- Rodríguez, Ángel
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2022-02-08
- Volume
- 327
- Issue
- 6
- Pages
- 534
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC8826179
- OpenAlex
- W4210940103
- Cited by
- 597
- References
- 17
- Citations by year
- 2026: 105 · 2025: 153 · 2024: 151 · 2023: 124 · 2022: 64
- FWCI
- 91.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Keywords
- tirzepatide, insulin glargine, type 2 diabetes, glycemic control, HbA1c, GIP/GLP-1 receptor agonist, combination therapy, metformin, body weight, adverse events, drug safety, treatment discontinuation, inadequate glycemic control, dose escalation, hypoglycemia, nausea, vomiting
- MeSH terms
- Insulin Glargine, Glycemic Control, Tirzepatide, Blood Glucose, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Gastric Inhibitory Polypeptide, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Male, Metformin, Middle Aged, Weight Loss
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 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (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
