Three-year SURMOUNT-1 data show a 94% cut in progression to type 2 diabetes

Eli Lilly announced topline results on August 20, 2024, from the three-year portion of its SURMOUNT-1 trial, reporting that weekly tirzepatide — sold as Zepbound for weight management and Mounjaro for type 2 diabetes — cut the risk of progressing to type 2 diabetes by 94% compared with placebo in adults with prediabetes who had obesity or were overweight ^[1]. It is the longest completed trial of tirzepatide to date ^[1].

The analysis covered 1,032 participants who had prediabetes when they were randomized and who stayed in the study for an additional 104 weeks of treatment beyond the original 72-week endpoint, for a total treatment period of 176 weeks, followed by 17 weeks off treatment — 193 weeks in all ^[1]. The original 72-week results were published in the New England Journal of Medicine in 2022 ^[1].

What the numbers showed

On the diabetes-progression endpoint, pooled tirzepatide doses (5 mg, 10 mg and 15 mg) produced a 94% risk reduction versus placebo through week 176 using what Lilly calls the efficacy estimand, and a 93% reduction using the treatment-regimen estimand, which accounts for people who stopped treatment or started other therapies ^[1]. Both were statistically significant (p<0.0001) ^[1].

Weight loss held up over the three years. Under the efficacy estimand, average weight reductions at week 176 were 15.4% on 5 mg, 19.9% on 10 mg and 22.9% on 15 mg, versus 2.1% for placebo ^[1]. Under the more conservative treatment-regimen estimand, the figures were 12.3%, 18.7% and 19.7%, versus 1.3% for placebo ^[1]. The 10 mg and 15 mg comparisons against placebo were statistically significant (p<0.001) ^[1].

What happened after people stopped mattered too. During the 17-week off-treatment follow-up, participants who had discontinued tirzepatide began regaining weight and showed some increase in progression to type 2 diabetes; the risk reduction versus placebo narrowed to 88% ^[1].

Safety over 193 weeks was consistent with the earlier 72-week results and other tirzepatide weight-management trials, Lilly said ^[1]. The most frequent adverse events were gastrointestinal and generally mild to moderate, most commonly diarrhea, nausea, constipation and vomiting ^[1].

Why it matters for patients

Prediabetes is common, and many people taking GLP-1 or GIP/GLP-1 medicines for weight have it. These data are the first from a completed three-year tirzepatide trial to quantify how much staying on the drug shifted the odds of crossing into type 2 diabetes in this group ^[1]. A BMO Capital Markets analyst told Reuters, "We just don't see numbers like this in metabolic space," and noted that Novo Nordisk's drug had shown a 73% risk reduction after three years in a separate late-stage trial ^[2]. Those were different studies, so the figures are not a head-to-head comparison.

The off-treatment data are the other practical signal: benefits narrowed once people stopped, with weight regain and some increase in diabetes progression ^[1]. That is relevant because adherence in real-world use is often short. Reuters reported in July 2024 that only one in four U.S. patients prescribed Wegovy or Ozempic (both semaglutide) for weight loss two years earlier were still taking them ^[2].

Importantly, tirzepatide is not approved to prevent or delay type 2 diabetes. It was approved as Mounjaro for glycemic control in adults with type 2 diabetes on May 13, 2022, and as Zepbound for chronic weight management on November 8, 2023 ^[1]. A Leerink analyst said it was unclear whether Lilly could file for a prevention indication based on these data, and that a prediabetes approval could be significant for the company ^[2]. Whether Lilly will seek such an indication was not stated in the announcement.

What happens next

Lilly said detailed results would be submitted to a peer-reviewed journal and presented at ObesityWeek 2024, held November 3–6 ^[1]. The company also noted ongoing tirzepatide studies in chronic kidney disease and in obesity-related morbidity and mortality, a 2024 submission to the FDA for moderate-to-severe obstructive sleep apnea with obesity, and plans to submit heart failure with preserved ejection fraction data later that year ^[1].