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Molecular Formula | C225H348N48O68 |
CAS Number | 2023788-19-2 |
Molar Mass | 4813.527 g/mol |
Amino Acid Sequence | YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS |
PubChem CID | 154666422 |
Primary Research Area |
Type 2 Diabetes Mellitus (T2DM) Obesity Weight Management Glycemic Control HbA1c Reduction Cardiovascular Outcomes (CVOT) Non-alcoholic Steatohepatitis (NASH) / Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Insulin Resistance Glucagon-Like Peptide-1 (GLP-1) Receptor Agonism Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Agonism Appetite Suppression Body Composition Renal Outcomes |
Purity | >99% |
Research Summary | Description |
---|---|
Once-weekly Tirzepatide in patients with Type 2 diabetes |
Summary: This publication reports the results of SURPASS-1, a Phase 3, randomized, double-blind, placebo-controlled trial evaluating tirzepatide as monotherapy in adults with type 2 diabetes who were treatment-naive. Participants received once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 40 weeks. All three doses of tirzepatide significantly reduced HbA1c and body weight from baseline compared to placebo. Notably, a high percentage of participants achieved HbA1c levels below 7% and even below 5.7% (non-diabetic range). Gastrointestinal adverse events (nausea, diarrhea, vomiting) were the most common. Citation: Rosenstock, J., Wysham, P. C., Frías, J. P., Kaneko, S., Kawaguchi, Y., Manghi, F. P., ... & SURPASS-1 Investigators. (2021). Once-weekly tirzepatide in patients with type 2 diabetes. The New England Journal of Medicine, 385(6), 503–515. |
Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial |
Summary: SURPASS-4 was a Phase 3, open-label, randomized trial comparing tirzepatide (5 mg, 10 mg, or 15 mg once weekly) with insulin glargine once daily in patients with type 2 diabetes and increased cardiovascular risk whose glucose levels were inadequately controlled. The study's primary objective was to assess glycemic control, with a median follow-up of 85 weeks. Tirzepatide demonstrated superior HbA1c reductions and significantly greater weight loss compared to insulin glargine. Importantly, tirzepatide was associated with a lower risk of hypoglycemia compared to insulin glargine. The trial also showed a numerically lower rate of major adverse cardiovascular events (MACE) with tirzepatide, though it was not powered for MACE superiority. Citation: Del Prato, S., Kahn, S. E., Pavo, I., Lukashevich, V., Kozlovitski, D., Dahl, D., ... & SURPASS-4 Investigators. (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. The Lancet, 398(10302), 1435–1446. |
Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial (SURPASS-3 MRI) |
Summary: This post-hoc analysis of the SURPASS-3 MRI substudy investigated the impact of tirzepatide (pooled doses of 5 mg, 10 mg, and 15 mg) versus insulin degludec on thigh muscle volume, muscle volume Z-score (a measure invariant to weight), and muscle fat infiltration in patients with type 2 diabetes. Using MRI, the study found that while tirzepatide-induced weight reduction was associated with a decrease in absolute muscle volume, the changes in muscle volume were in line with what would be expected for the degree of weight loss observed. Crucially, tirzepatide significantly reduced muscle fat infiltration (myosteatosis) more favorably than insulin degludec, suggesting improved muscle quality. Citation: Sattar, N., Abadir, E., Ambery, P., Drouin, P., Frias, J. P., Lingvay, I., ... & SURPASS-3 MRI investigators. (2025). Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial (SURPASS-3 MRI). The Lancet Diabetes & Endocrinology, 13(2), 174-184. |
Comparison of tirzepatide with dulaglutide on major cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: The SURPASS-CVOT trial. |
Summary: This highly anticipated Phase 3, event-driven, randomized, double-blind, active-controlled trial (SURPASS-CVOT) compared once-weekly tirzepatide (at maximum tolerated doses up to 15 mg) with once-weekly dulaglutide (1.5 mg) in over 13,000 adults with type 2 diabetes and established atherosclerotic cardiovascular disease. The primary objective was to demonstrate non-inferiority of tirzepatide to dulaglutide for major adverse cardiovascular events (MACE-3: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Topline results, recently announced, indicate that tirzepatide met the primary objective of non-inferiority, showing an 8% lower rate of MACE-3 events compared to dulaglutide (Hazard Ratio: 0.92; 95.3% CI: 0.83 to 1.01), which fell within the non-inferiority margin. Furthermore, while not primarily powered for superiority, tirzepatide also demonstrated numerically greater reductions in HbA1c and weight, and was associated with a 16% lower rate of all-cause death compared to dulaglutide. Citation: Eli Lilly and Company. (2025, July 31). Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial, reinforcing its benefit in patients with type 2 diabetes and heart disease. Retrieved from https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated |
Summary: This publication reports the results of SURPASS-1, a Phase 3, randomized, double-blind, placebo-controlled trial evaluating tirzepatide as monotherapy in adults with type 2 diabetes who were treatment-naive. Participants received once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 40 weeks. All three doses of tirzepatide significantly reduced HbA1c and body weight from baseline compared to placebo. Notably, a high percentage of participants achieved HbA1c levels below 7% and even below 5.7% (non-diabetic range). Gastrointestinal adverse events (nausea, diarrhea, vomiting) were the most common.
Citation:
Rosenstock, J., Wysham, P. C., Frías, J. P., Kaneko, S., Kawaguchi, Y., Manghi, F. P., ... & SURPASS-1 Investigators. (2021). Once-weekly tirzepatide in patients with type 2 diabetes. The New England Journal of Medicine, 385(6), 503–515.
Summary: SURPASS-4 was a Phase 3, open-label, randomized trial comparing tirzepatide (5 mg, 10 mg, or 15 mg once weekly) with insulin glargine once daily in patients with type 2 diabetes and increased cardiovascular risk whose glucose levels were inadequately controlled. The study's primary objective was to assess glycemic control, with a median follow-up of 85 weeks. Tirzepatide demonstrated superior HbA1c reductions and significantly greater weight loss compared to insulin glargine. Importantly, tirzepatide was associated with a lower risk of hypoglycemia compared to insulin glargine. The trial also showed a numerically lower rate of major adverse cardiovascular events (MACE) with tirzepatide, though it was not powered for MACE superiority.
Citation:
Del Prato, S., Kahn, S. E., Pavo, I., Lukashevich, V., Kozlovitski, D., Dahl, D., ... & SURPASS-4 Investigators. (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. The Lancet, 398(10302), 1435–1446.
Summary: This post-hoc analysis of the SURPASS-3 MRI substudy investigated the impact of tirzepatide (pooled doses of 5 mg, 10 mg, and 15 mg) versus insulin degludec on thigh muscle volume, muscle volume Z-score (a measure invariant to weight), and muscle fat infiltration in patients with type 2 diabetes. Using MRI, the study found that while tirzepatide-induced weight reduction was associated with a decrease in absolute muscle volume, the changes in muscle volume were in line with what would be expected for the degree of weight loss observed. Crucially, tirzepatide significantly reduced muscle fat infiltration (myosteatosis) more favorably than insulin degludec, suggesting improved muscle quality.
Citation:
Sattar, N., Abadir, E., Ambery, P., Drouin, P., Frias, J. P., Lingvay, I., ... & SURPASS-3 MRI investigators. (2025). Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial (SURPASS-3 MRI). The Lancet Diabetes & Endocrinology, 13(2), 174-184.
Summary: This highly anticipated Phase 3, event-driven, randomized, double-blind, active-controlled trial (SURPASS-CVOT) compared once-weekly tirzepatide (at maximum tolerated doses up to 15 mg) with once-weekly dulaglutide (1.5 mg) in over 13,000 adults with type 2 diabetes and established atherosclerotic cardiovascular disease. The primary objective was to demonstrate non-inferiority of tirzepatide to dulaglutide for major adverse cardiovascular events (MACE-3: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Topline results, recently announced, indicate that tirzepatide met the primary objective of non-inferiority, showing an 8% lower rate of MACE-3 events compared to dulaglutide (Hazard Ratio: 0.92; 95.3% CI: 0.83 to 1.01), which fell within the non-inferiority margin. Furthermore, while not primarily powered for superiority, tirzepatide also demonstrated numerically greater reductions in HbA1c and weight, and was associated with a 16% lower rate of all-cause death compared to dulaglutide.
Citation:
Eli Lilly and Company. (2025, July 31). Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial, reinforcing its benefit in patients with type 2 diabetes and heart disease. Retrieved from https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated
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