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Lilly's Mounjaro rivals Trulicity in cardiovascular risk reduction

Mounjaro rivals its GLP-1 predecessor, Trulicity, in reducing cardiovascular events in type 2 diabetes and outperforms in A1C reduction, weight loss and cardiovascular biomarkers.

Alivia Kaylor, MSc
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Published: 01 Aug 2025

Eli Lilly's dual GIP/GLP-1 drug, Mounjaro, has moved one step closer to receiving a cardiovascular risk reduction label following Phase 3 trial data showing that the therapy performed on par with the company's own GLP-1 predecessor, Trulicity, in a head-to-head study.

The SURPASS-CVOT study, which enrolled 13,299 patients across 30 countries with type 2 diabetes and established cardiovascular disease, met its primary objective by demonstrating that Mounjaro (tirzepatide) was noninferior to Trulicity (dulaglutide) in reducing major adverse cardiovascular events (MACE-3), including cardiovascular death, heart attack and stroke.

Study participants displayed an 8% lower risk of cardiovascular events than those using Trulicity, with consistent results across all three MACE-3.

Additionally, Lilly says, the 4.5-year-long study found that Mounjaro led to more weight loss, reduced A1C levels and was associated with a 16% lower rate of death by all causes.

"The SURPASS-CVOT results show that Mounjaro preserved the cardioprotective benefit of Trulicity … while providing additional benefits, including greater kidney protection and a reduced overall risk of death," said Kenneth Custer, PhD, president of Lilly Cardiometabolic Health. "These findings strengthen the case for Mounjaro as a potential front-line treatment for people with type 2 diabetes and cardiovascular disease."

Industry implications

Globally, diabetes affects more than 530 million people (10.5% of the global population). Among those individuals with type 2 diabetes, cardiovascular disease remains the leading cause of death, studies have confirmed.

"Historically, cardiovascular risk reduction in type 2 diabetes came through statins or antihypertensives," Lydia Alexander, MD, Immediate Past President of the Obesity Medicine Association and Chief Medical Officer at Enara Health, said in response to Lilly's press announcement. "Now, metabolic therapies are joining the front line and SURPASS-CVOT signals tirzepatide's arrival as a contender in that realm."

Unlike traditional treatment methods targeting isolated risk factors, dual agonists like tirzepatide address the interconnected factors of cardiometabolic disease, which include insulin resistance, excess adiposity and systemic inflammation.

"Providers will increasingly view GLP-1/GIP dual agonists as integral to cardiovascular risk reduction -- not just weight or glycemic control," Alexander added. "Improvements in renal function, weight and glycemic control suggest tirzepatide may exert broader multi-organ benefits."

A switch to a whole-body approach to treating metabolic disease, especially among patients with overlapping comorbidities, could improve how clinicians assess cardiovascular risk and help prioritize early intervention. These clinical results also offer care providers a promising single-agent approach to managing glucose levels, weight and cardiovascular and renal disease.

"An 8% MACE reduction may seem modest, but it meets rigorous criteria," Alexander highlighted. "If the 16% mortality reduction holds, therapy algorithms could shift dramatically."

Submission timeline

According to the press release, Lilly intends to submit the trial data to the global regulatory authorities by the end of this year, potentially matching the indication granted in 2020 to Novo Nordisk's Ozempic (semaglutide). A cardiovascular label could also ease payer negotiations for dual-purpose reimbursement.

Full results will be detailed at the European Association for the Study of Diabetes meeting in September.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.

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