Semaglutide (CSPC Zhongqi)

A phase 3 trial of Eli Lilly's Mounjaro versus Trulicity has achieved its primary endpoint, showing Mounjaro's noninferiority in reducing cardiovascular risks in patients with Type 2 diabetes and heart disease. A variety of GLP-1 drugs that were developed to treat Type 2 diabetes, including Novo Nordisk’s Ozempic, have secured label expansions to reduce the risk of cardiovascular issues.But what about Eli Lilly’s dual-action GIP/GLP-1 therapy Mounjaro?Lilly has presented results from a phase 3 trial in which Mounjaro measures up head-to-head against the company’s GLP-1 Trulicity in reducing cardiovascular risks in patients with Type 2 diabetes and heart disease.The Surpass-CVOT study achieved its primary objective with Mounjaro showing its noninferiority to Trulicity in reducing the three major adverse cardiovascular events (MACE-3)—cardiovascular death, heart attack or stroke. Trulicity, which was approved to treat Type 2 diabetes in 2014, gained an FDA nod to reduce the risk of cardiovascular problems six years later. In the trial, which included 13,299 patients in 30 countries and lasted four-plus years, Mounjaro patients had an 8% lower risk of cardiovascular events than those on Trulicity, with the results consistent across each of the three components of MACE-3.Additionally, Mounjaro triggered more weight loss and reduced the level of A1C, which is a biomarker for Type 2 diabetes. Mounjaro also was associated with a 16% lower rate of death by all causes, suggesting its overall health benefits, Lilly said.“Cardiovascular disease remains the leading cause of death among people living with Type 2 diabetes,” Kenneth Custer, Ph.D., who heads up Lilly’s cardiometabolic health unit, said in a release. “These findings strengthen the case for Mounjaro as a potential front-line treatment for people with type 2 diabetes and cardiovascular disease.” Lilly added that it will submit the results to regulatory authorities by the end of this year. In September, the company will present detailed data from the trial at the European Association for the Study of Diabetes conference in Vienna.While Lilly called it a "landmark" trial, analysts from Citi weren't quite as enthusiastic, writing in a note to clients that it "misses the superiority scenario that many investors had hoped for."The analysts added that during an event in April, however, top cardiologists said "even a non-inferiority outcome would be sufficient for docs to change prescribing habits given tirzepatide's superior weight loss and tolerability profile vs. Novo's semaglutide." Tirzepatide is Mounjaro's generic name.Citi also took note of Lilly's report that a pre-specified indirect comparison of matched patient-level data from the Rewind-CVOT study, which compared Trulicity to placebo, and the Surpass-CVOT trial demonstrated Mounjaro reduced the risk of MACE-3 by 28% and all-cause mortality by 39% compared to a putative placebo, "which is a significant reduction and meets the 20% bar that cardiologists cite as being clinically meaningful."The heart-helping benefits of GLP-1 drugs have been well established. In 2020, Novo’s megablcockbuster Ozempic was approved to reduce cardiovascular risks in Type 2 diabetes patients. Then, earlier this year, Ozempic scored a nod to reduce the risk of worsening kidney disease and cardio death in those with Type 2 diabetes and chronic kidney disease. In 2024, the FDA tacked on a cardio expansion for Ozempic's weight loss counterpart Wegovy for those who are overweight or obese. Novo is also working to gain a heart failure nod for Wegovy and a cardio risk reduction endorsement for its oral GLP-1 treatment Rybelsus.As for Lilly, it won an expansion last year for its GIP/GLP-1 Zepbound to become the first treatment for patients with obesity and sleep apnea. The company also is testing its dual-action drugs as treatments for heart failure, prediabetes and metabolic dysfunction-associated steatohepatitis.