An experimental Eli Lilly drug led to greater improvement on measures of type 2 diabetes compared to the approved Novo drug Ozempic, Phase 3 results that further build the case for the closely watched peptide that’s engineered to hit three metabolic targets in the gut.
The preliminary results are from a Phase 3 trial that evaluated two doses of the Lilly drug retatrutide in adults with type 2 diabetes. Lilly said Wednesday that both the high and low doses of the study drug met the main goal, reducing A1C, a measure of blood sugar, by an average 2.2 percentage points at 80 weeks. By comparison, the highest approved dose of Ozempic reduced A1C by 1.8 percentage points.
On the key secondary goal of measuring body weight at 80 weeks, the study drug led patients to lose an average of 44.3 pounds (about 19.5% of body weight) for the low dose and 47.4% (about 20.9%) for the high dose. In the Ozempic arm, patients lost an average 20.9 pounds (about 9.4% of body weight) at 80 weeks. The results also showed retatrutide topped Ozempic on cardiovascular measures, such as non-HDL cholesterol, triglycerides, and systolic blood pressure. Lilly said detailed data will be presented at a future medical meeting and published in a peer-reviewed publication.
“Based on these results and those from across our Phase 3 program, we believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions,” Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, said in a prepared statement.
Retatrutide is a peptide engineered to bind to and activate three receptors in the gut: GLP-1, GIP, and glucagon. The once-weekly injectable drug sometimes goes by the shorthand “triple-G.” While hitting three targets is intended to lead to better results, it also leads to greater side effects, notably the gastrointestinal problems that patients cite when stopping use of peptide drugs for metabolic indications.
The most common adverse events reported in the study were constipation, vomiting, and indigestion. Both the high and low doses of the study drug posted higher rates of these side effects compared to Ozempic. The discontinuation rates were also higher — 4.8% and 7.9% for the low and high doses respectively, compared to 2.7% for Ozempic.
Lilly already hits GLP-1 and GIP with tirzepatide, an approved peptide drug that’s marketed as Mounjaro for type 2 diabetes and as Zepbound for weight management. Meanwhile, Novo’s semaglutide, marketed as Ozempic for type 2 diabetes and as Wegovy for obesity, only targets the GLP-1 receptor.
In a research note, Leerink Partners analyst David Risinger said the head-to-head data strengthen the case for retatrutide’s long-term differentiation, supporting branded premium pricing ahead of the launch of generic versions of Ozempic, whose patents expire in 2032. Risinger acknowledged the higher rates of gastrointestinal side effects and discontinuations, adding that they are a tradeoff for triple-G. But he added that these problems are not a surprise and the tolerability issues are essentially in line with what Lilly reported earlier this year from a different Phase 3 test that enrolled patients with obesity who also have type 2 diabetes.
The latest retatrutide results are part of a broad Phase 3 program for the drug. In total, Lilly is testing the peptide in nine Phase 3 trials in chronic weight management and related conditions, plus three more Phase 3 tests in type 2 diabetes. Risinger said the next key data readout to watch for is the Phase 3 test comparing retatrutide head to head against tirzepatide in adults with obesity, both with or without type 2 diabetes. If retatrutide reaches the market, Leerink models the drug reaching about $15 billion in sales in 2032.
Photo: Konrad Fiedler/Bloomberg, via Getty Images
