Tirzepatide Shows Noninferiority to Dulaglutide for Rate of MACE
In the study, tirzepatide (Mounjaro) improved measures of A1c, weight, renal function, and all-cause mortality.
In the SURPASS-CVOT (NCT04255433) study, tirzepatide (Mounjaro) showed noninferiority compared with dulaglutide (Trulicity) for the rate of major adverse cardiovascular events (MACE-3), which included cardiovascular death, heart attack, and stroke. Further, investigators found that tirzepatide improved measures of A1c, weight, renal function, and all-cause mortality.1
In the study, tirzepatide (Mounjaro) improved measures of A1c, weight, renal function, and all-cause mortality. | Image Credit: Siarhei - stock.adobe.com
"Cardiovascular disease remains the leading cause of death among people living with type 2 diabetes," Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, said in a news release.1 "The SURPASS-CVOT results show that Mounjaro preserved the cardioprotective benefit of Trulicity, a GLP-1 receptor agonist, while providing additional benefits, including greater kidney protection and a reduced overall risk of death. These findings strengthen the case for Mounjaro as a potential front-line treatment for people with type 2 diabetes and cardiovascular disease."
In the study, investigators aimed to determine the efficacy and safety of tirzepatide compared to dulaglutide for individuals with type 2 diabetes (T2D) and increased cardiovascular risk. Patients included had a diagnosis of T2D, confirmed atherosclerotic cardiovascular disease, hemoglobin A1c of 7% to 10.5%, and a body mass index of 25 kg/m2 or more. Patients excluded had type 1 diabetes, MACE within the last 60 days, a history of pancreatitis, and more.2
Treatment included either once weekly tirzepatide or dulaglutide administered subcutaneously. The primary outcome included time to first occurrence of death from MACE-3, and secondary outcomes included time to death from any cause, time to cardiovascular death, time to first myocardial infarction, time to first occurrence of stroke, change from baseline in body weight, change from baseline in hemoglobin A1c, change from baseline in blood lipids, and time to first occurrence of revascularization.2
Investigators of the study found that the risk of MACE-3 was 8% lower for tirzepatide compared with dulaglutide and met the prespecified criteria for noninferiority. Additionally, tirzepatide had consistent results across all 3 components of MACE-3. For all-cause mortality, the rate was 16% lower for tirzepatide when compared with dulaglutide. When looking at the change in eGFR for those with chronic kidney disease, there was a decrease of 4.97 mL/min/1.73 m2 for tirzepatide and 8.51 mL/min/1.73 m2 for dulaglutide. For A1c, there were reductions of 1.73% and 0.90%, respectively, and body weight decreased by 12.6% and 4.95%, respectively.1
The safety and tolerability of both drugs remained consistent with what has already been established, and the most commonly reported adverse events (AEs) for both were gastrointestinal-related and were generally mild-to-moderate in severity. Approximately 13.3% of those taking tirzepatide and 10.2% taking dulaglutide discontinued treatment due to AEs.1
In another study published in eClinicalMedicine, investigators found that tirzepatide had the greatest weight loss and strongest antihypertensive effects among popular antiobesity medications, including semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), orlistat (Xenical), naltrexone/bupropion (Contrave), phentermine/topiramate (Qsymia), naltrexone (Vivitrol), bupropion (Wellbutrin, Zyban), phentermine (Adipex), and topiramate (Topamax, Topiragen). For cardiovascular effects, tirzepatide had the strongest effects on systolic and diastolic blood pressure as well as improvements in triglyceride, high-density lipoprotein cholesterol, fasting glucose, and glycated hemoglobin A1c.3
READ MORE: Cardiology Resource Center
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REFERENCES
1. 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. News release. Eli Lilly. July 31, 2025. Accessed August 4, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated
2. A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT). ClinicalTrials.gov identification: NCT04255433. Updated July 23, 2025. Accessed August 4, 2025. https://clinicaltrials.gov/study/NCT04255433
3. Gallagher A. Tirzepatide facilitates greater weight loss, strongest antihypertensive effects. Drug Topics. February 13, 2025. Accessed August 4, 2025. https://www.drugtopics.com/view/tirzepatide-facilitates-greater-weight-loss-strongest-antihypertensive-effects
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