Background: Obesity is a chronic disease and a causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period.
Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.
Method: We performed a phase 3, double-blind, randomized, controlled trial in which 2,539 participants with obesity, of whom 1,032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at an once-weekly dose of 5 mg, 10 mg, or 15 mg, or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The 3 key secondary endpoints, which were controlled for false positives, were the % change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods.
Results: At 176 weeks, the mean % change in body weight among the participants who received tirzepatide was −12.3% with the 5-mg dose, −18.7% with the 10-mg dose, and −19.7% with the 15-mg dose, as compared with −1.3% among those who received placebo (p < 0.001 for all comparisons with placebo).
Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0–0.1; p < 0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1–0.2; p < 0.001).
Other than COVID-19, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified.
Conclusion: 3 years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo.
(Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.)
