INDIANAPOLIS, IN - Eli Lilly recently announcedEli Lilly and Company positive topline results from the SURMOUNT-1 three-year study (176-week treatment period) evaluating the efficacy and safety of tirzepatide (Zepbound^® and Mounjaro^®) once weekly for long-term weight management and delay in progression to diabetes in adults with pre-diabetes and obesity or overweight. Weekly tirzepatide injections (5 mgⁱ, 10 mg, 15 mg) significantly reduced the risk of progression to type 2 diabetes by 94% ⁱⁱ among adults with pre-diabetes and obesity or overweight compared to placebo. Additionally, treatment with tirzepatide resulted in sustained weight loss through the treatment period, with adults on the 15 mg dose experiencing a 22.9% average decrease in body weight compared to 2.1% for placebo in adults with pre-diabetes and obesity or overweight at the end of the treatment period.

"Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the three-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes."

Tirzepatide was evaluated in 1,032 adults who had pre-diabetes at randomization and obesity or overweight for a treatment period of 176 weeks, followed by a 17-week off-treatment period (193 weeks in total). Results from the SURMOUNT-1 phase 3 study's primary analysis at 72 weeks in all participants were published in the New England Journal of Medicine in 2022.

In a key secondary endpoint, tirzepatide led to a significant reduction in the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.0001, controlled for type 1 error). For the efficacy estimandⁱⁱ, pooled doses of tirzepatide achieved significant results, demonstrating a 94% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176. For the treatment-regimen estimandⁱⁱⁱ, pooled doses of tirzepatide resulted in a significant 93% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176.

In an additional key secondary endpoint, tirzepatide (10 mg and 15 mg) led to statistically significant weight reduction compared to placebo in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.001, controlled for type 1 error). For the efficacy estimandⁱⁱ, adults taking tirzepatide achieved average weight reductions of 15.4% (5 mgⁱ), 19.9% (10 mg) and 22.9% (15 mg) compared to placebo (2.1%) at week 176. For the treatment-regimen estimandⁱⁱⁱ, adults taking tirzepatide achieved average weight reductions of 12.3% (5 mg ⁱ), 18.7% (10 mg) and 19.7% (15 mg) compared to placebo (1.3%) at week 176.

During the 17-week off-treatment follow-up period, those who had discontinued from tirzepatide began to regain weight and had some increase in the progression to type 2 diabetes, resulting in an 88% reduction (p<0.0001, controlled for type 1 error) in the risk of progression to type 2 diabetes compared to placebo.

The overall safety and tolerability profile of tirzepatide over the 193-week study was consistent with the previously published primary results at 72 weeks in SURMOUNT-1 and other tirzepatide clinical studies conducted for chronic weight management. The most frequently reported adverse events were typically gastrointestinal-related and generally mild to moderate in severity. The most common gastrointestinal-related adverse events for patients treated with tirzepatide were diarrhea, nausea, constipation and vomiting.

Tirzepatide, a GIP and GLP-1 receptor agonist, works by activating the two hormone receptors. GLP-1 is a regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. In addition, tirzepatide stimulates insulin secretion in a glucose-dependent manner. Tirzepatide increases insulin sensitivity in patients with type 2 diabetes mellitus and these effects can lead to a reduction of blood glucose.

These topline results provide evidence for reduced risk of progression to type 2 diabetes and long-term maintenance of weight loss with tirzepatide in adults with pre-diabetes and obesity or overweight. Detailed results will be submitted to a peer-reviewed journal and presented at ObesityWeek 2024, which will take place November 3-6.