Lilly says tirzepatide cut type 2 diabetes risk by 94% in three-year trial

Eli Lilly said on Aug. 20, 2024 that tirzepatide, sold as Zepbound and Mounjaro, reduced the risk of progressing to type 2 diabetes by 94% in adults with prediabetes and obesity or overweight, compared with placebo, across 176 weeks of weekly injections ^[1].

The results come from SURMOUNT-1, a randomized, double-blind, placebo-controlled trial that began with 1,032 adults who had prediabetes when they were assigned to a treatment group ^[1]. After the original 72-week phase, those participants stayed enrolled for an additional 104 weeks of treatment, for a total treatment period of 176 weeks, followed by 17 weeks with no drug — 193 weeks overall ^[1]. Lilly described it as the longest completed trial of tirzepatide to date ^[1].

On the study's key secondary endpoint, pooled tirzepatide doses produced a 94% reduction in the risk of progression to type 2 diabetes versus placebo, with a p-value below 0.0001 ^[1]. Lilly reported a second figure of 93% using a different accounting method that includes people who stopped taking the drug ^[1].

Weight loss was sustained through the treatment period. Averaged across those who stayed on treatment, participants lost 15.4% of body weight at the 5 mg dose, 19.9% at 10 mg and 22.9% at 15 mg, compared with 2.1% for placebo ^[1]. Under the method that counts everyone as originally assigned, the figures were 12.3%, 18.7% and 19.7%, against 1.3% for placebo ^[1].

When treatment stopped, participants began regaining weight and showed some increase in progression to type 2 diabetes, leaving an 88% reduction in risk compared with placebo over the full study period ^[1].

The safety profile over 193 weeks matched what was seen in the earlier 72-week results and in other tirzepatide trials for chronic weight management, Lilly said. The most common side effects were gastrointestinal — diarrhea, nausea, constipation and vomiting — and were generally mild to moderate ^[1]. The number of participants who stopped treatment because of side effects has not been reported.

Reuters reported that Lilly shares rose 4.4% to $962.02 in early trading after the announcement ^[2]. BMO Capital Markets analyst Evan Seigerman said, "We just don't see numbers like this in metabolic space," and noted that a rival drug from Novo Nordisk showed a 73% risk reduction after three years in a separate late-stage trial ^[2]. Leerink analyst David Risinger said it was unclear whether Lilly could file for approval to prevent diabetes based on the data ^[2]. Reuters also noted that only one in four U.S. patients prescribed Novo's Wegovy or Ozempic for weight loss two years earlier were still taking the medications ^[2].

Why it matters for patients

Prediabetes and obesity together place people at elevated risk of developing type 2 diabetes, and the trial was designed to test whether long-term treatment changes that trajectory ^[1]. The 94% figure is a relative reduction — how much the risk was lowered compared with placebo — not the share of people who avoided diabetes. The actual number of participants who developed diabetes in each group has not been disclosed, so an individual's absolute change in risk cannot be calculated from these results.

Tirzepatide is a GIP and GLP-1 receptor agonist, a single molecule that activates both hormone receptors ^[1]. Its approved uses are type 2 diabetes for Mounjaro, cleared by the FDA on May 13, 2022, and chronic weight management for Zepbound, approved Nov. 8, 2023, for adults with obesity or those who are overweight with at least one weight-related condition ^[1]. Preventing diabetes is not an approved use.

The data also indicate that the benefit depended on continuing treatment. During the 17 weeks after the drug was stopped, weight returned and the risk reduction weakened from 94% to 88% ^[1]. The longer-term effects of stopping and restarting have not been reported.

What happens next

Detailed results are to be submitted to a peer-reviewed journal and presented at ObesityWeek 2024, scheduled for Nov. 3-6 ^[1]. Whether Lilly will seek FDA approval for a diabetes-prevention indication has not been disclosed ^[2].