INDIANAPOLIS, IN - Eli Lilly and Company announced detailed results from the Phase 3 SURMOUNT-1 three-year study (176-week treatment period), the longest completed study to date of tirzepatide. Weekly tirzepatide (Zepbound^® and Mounjaro^®) injections (pooled 5 mg, 10 mg, 15 mg doses) significantly reduced the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight, compared with placebo, over 176 weeks. Tirzepatide demonstrated sustained average weight loss of 22.9% (15 mg dose) through the three-year treatment period for the efficacy estimand. These findings were published in The New England Journal of Medicine (NEJM) and recently presented at ObesityWeek 2024.

"Individuals treated with tirzepatide lost on average up to 23% of their body weight and maintained this for over three years, while benefitting from a substantial decrease in risk of developing type 2 diabetes. In absolute terms, nearly 99% of individuals treated with tirzepatide remained diabetes-free at 176 weeks," said Ania Jastreboff, M.D., Ph.D., director of the Yale Obesity Research Center. "These results are impressive given the degree of sustained weight reduction and decrease in risk of diabetes."

Tirzepatide is the first and only approved dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist medicine. Both GIP and GLP-1 are gut hormones secreted in response to nutrient load and are responsible for the incretin effect.

"In the SURMOUNT-1 three-year study of tirzepatide, an average weight reduction of up to 22.9% was accompanied by a hazard ratio of 0.06 for progression to type 2 diabetes. This translates to a risk reduction of 94% and a number needed to treat of nine to prevent one case of diabetes," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "These results underscore the critical role of long-term therapy with effective treatments like tirzepatide to achieve and maintain weight reduction."  

In additional endpoints, the study showed an association of tirzepatide treatment with improvements in glycemic control, cardiometabolic risk factors (including fasting insulin, blood pressure and lipids) and health-related quality of life, which were sustained through 176 weeks. A post hoc mediation analysis suggested that approximately half of the observed effect in delay to onset of type 2 diabetes with tirzepatide was associated with medication-induced weight reduction, with the remaining benefit potentially attributed to other effects of tirzepatide.

The overall safety and tolerability profile of tirzepatide at 193 weeks (176 weeks followed by 17 weeks off-treatment) was consistent with the previously published results at 72 weeks for SURMOUNT-1 and other tirzepatide clinical studies conducted for weight reduction and long-term maintenance. Other than COVID-19, the most frequently reported adverse events were gastrointestinal-related and generally mild to moderate in severity. The most common gastrointestinal-related adverse events in patients treated with tirzepatide were nausea, diarrhea and constipation.