SURMOUNT-1 was a phase 3, double-blind, randomized study of tirzepatide 5, 10, and 15 mg once weekly compared with placebo in 2539 adults with obesity, or overweight with at least one weight-related comorbidity, without T2D for an initial 72-weeks.2

Following the initial 72 weeks, the 1,032 participants who had prediabetes at study commencement remained enrolled in SURMOUNT-1 for an additional 104 weeks of treatment to evaluate the impact on body weight and potential differences in progression to T2D at 3 years of treatment with tirzepatide compared to placebo.3

Key secondary objectives were to demonstrate that tirzepatide was superior to placebo for

• time to onset of T2D at 176 weeks and 193 weeks (after 17 weeks off drug safety follow up period), and
• mean percent change in body weight from randomization to week 176.2
  

In a key secondary endpoint, tirzepatide led to a significant reduction in the risk of progression to T2D in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.0001, controlled for type 1 error).3

Pooled doses of tirzepatide achieved significant results, demonstrating a 94% reduction in risk of progression to T2D compared to placebo up to week 176, for the efficacy estimand.3

At week 176, mean percent weight reductions (efficacy estimand, controlled for type 1 error) were

• 15.4% in the tirzepatide 5 mg arm
• 19.9% in the tirzepatide 10 mg arm
• 22.9% in the tirzepatide 15 mg arm, and
• 2.1% in the placebo arm.3

The efficacy estimand represents efficacy had all patients remained on randomized treatment for the entire planned treatment duration (up to 176 weeks).3

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 T2D, resulting in an 88% reduction in the risk of progression to T2D compared to placebo.3

The overall safety and tolerability profile of tirzepatide over the 193-week study was consistent with the primary results at 72 weeks in SURMOUNT-1 and other tirzepatide clinical studies conducted for chronic weight management.3

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.3

Eli Lilly and Company is continuing to evaluate the results of the 176-week data from the SURMOUNT-1 study. Results will be submitted to a peer-reviewed journal and presented at ObesityWeek 2024, which will take place November 3-6. Regulatory authorities throughout the world have different evidence requirements to obtain an indication for risk reduction of T2D. We recognize the importance of these data and will assess our options based on discussions with regulators.3,4