Tirzepatide kept nearly 99% of prediabetic adults diabetes-free at three years, Lilly says

Eli Lilly released detailed three-year results on Nov. 13, 2024 from SURMOUNT-1, the longest completed study of tirzepatide, showing that nearly 99% of adults with prediabetes and obesity or overweight who received weekly injections remained free of type 2 diabetes at 176 weeks ^[1]. The findings were published in the New England Journal of Medicine and presented at ObesityWeek 2024 ^[1][2]. Lilly first disclosed the top-line results in August ^[2].

Among the trial's 1,032 participants with prediabetes, 1.2% of those taking pooled tirzepatide doses of 5 mg, 10 mg or 15 mg had been diagnosed with type 2 diabetes by week 176, compared with 12.6% of those on placebo ^[1]. Lilly reported the numbers two ways: one estimate counts participants who stayed on their assigned treatment (1.2% versus 12.6%), while the other also accounts for people who stopped treatment (1.3% versus 13.3%) ^[1]. The hazard ratio was 0.06 and 0.07, respectively, which Lilly described as a 94% reduction in risk ^[1]. The company calculated that nine patients would need to be treated to prevent one new case of diabetes ^[1][2].

Weight loss was also sustained. Average body weight fell 22.9% at the 15 mg dose, 19.9% at 10 mg and 15.4% at 5 mg by week 176 under the first estimate, compared with 2.1% for placebo ^[1]. Under the second estimate, the 15 mg group averaged 19.7% and placebo 1.3% ^[1].

After treatment stopped, the gap narrowed but held. During the 17-week follow-up that ended at week 193, 2.4% of the pooled tirzepatide group had been diagnosed with type 2 diabetes versus 13.7% on placebo, a hazard ratio of 0.12 ^[1].

The study was run and funded by Lilly. SURMOUNT-1 was randomized, double-blind and placebo-controlled, and enrolled adults without type 2 diabetes who had obesity, or overweight plus at least one of hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease; participants also followed a reduced-calorie diet with increased physical activity ^[1].

A post hoc mediation analysis suggested about half of the delay in diabetes onset was associated with the weight loss produced by the drug, with the remaining benefit potentially from other effects ^[1]. Lilly also reported improvements in blood sugar control, fasting insulin, blood pressure, lipids and health-related quality of life that were sustained through 176 weeks ^[1][2]. Adverse events were mostly gastrointestinal — nausea, diarrhea and constipation were the most common — and generally mild to moderate, consistent with earlier results ^[1].

Why it matters for patients

Tirzepatide is sold as Mounjaro for type 2 diabetes and as Zepbound for adults with obesity or overweight plus a weight-related condition ^[1]. It is not approved to prevent diabetes, and whether Lilly will seek that indication has not been reported. Whether insurers would cover the drug for diabetes prevention has also not been reported.

The practical framing Lilly offered is the number needed to treat: nine people treated for three years to prevent one case of diabetes ^[1][2]. That is a measure of how many patients must take the drug for one to get the benefit the trial measured.

Two limits are worth noting. Everyone in this analysis had prediabetes plus obesity or overweight, so the results describe that group. And the week 193 figures show that the percentage of participants diagnosed with diabetes rose slightly in both groups in the 17 weeks after injections stopped, from 1.2% to 2.4% for tirzepatide and 12.6% to 13.7% for placebo ^[1].

Zepbound's label carries warnings about thyroid C-cell tumors, pancreatitis, gallbladder and kidney problems, low blood sugar when used with insulin or sulfonylureas, vision changes in people with type 2 diabetes, depression or suicidal thoughts, and the risk of food entering the lungs during surgery or procedures using deep sedation ^[1].

What happens next

The FDA is set to decide on using tirzepatide to treat moderate-to-severe obstructive sleep apnea; no decision date was disclosed ^[2]. Lilly plans to submit data on heart failure with preserved ejection fraction and obesity to the FDA and other regulators later this year ^[1][2]. Studies of tirzepatide in chronic kidney disease and in obesity-related illness and death are ongoing ^[1].