Three years of tirzepatide cut progression to type 2 diabetes by 94 percent in SURMOUNT-1

Three years of weekly tirzepatide injections sharply lowered the risk that adults with obesity and prediabetes would develop type 2 diabetes, compared with placebo, according to results from the SURMOUNT-1 trial published November 13, 2024, in the New England Journal of Medicine ^[1][2].

The trial enrolled 2,539 adults with obesity, and 1,032 of them also had prediabetes ^[1]. Those 1,032 participants stayed in the study for 176 weeks of treatment followed by a 17-week period with no drug, for a total of 193 weeks ^[1]. They were assigned to one of three once-weekly tirzepatide doses (5 mg, 10 mg or 15 mg) or to placebo ^[1].

At week 176, 1.3 percent of participants taking pooled tirzepatide doses had been diagnosed with type 2 diabetes, compared with 13.3 percent of those taking placebo (hazard ratio 0.07; 95% confidence interval, 0.0 to 0.1; P<0.001) ^[1]. In its announcement, Eli Lilly, which funded the trial, described this as a 94 percent reduction in the risk of progression to type 2 diabetes across all pooled doses ^[2]. The company also reported a number needed to treat of nine, meaning nine people with obesity and prediabetes would need to be treated for three years to prevent one new case of diabetes ^[2]. Lilly said nearly 99 percent of treated participants remained diabetes-free at 176 weeks ^[2].

Weight loss held up over the same period. In the analysis reported in the journal, the average change in body weight at 176 weeks was −12.3 percent with the 5 mg dose, −18.7 percent with 10 mg and −19.7 percent with 15 mg, compared with −1.3 percent for placebo ^[1]. Lilly also reported a set of figures calculated a different way, showing average reductions of 15.4 percent, 19.9 percent and 22.9 percent for the same three doses and 2.1 percent for placebo ^[2]. The two sets of numbers differ because of the statistical methods used, and the journal's abstract cites the more conservative figures ^[1][2].

After the 17-week off-treatment period, 2.4 percent of participants who had taken tirzepatide and 13.7 percent of those who had taken placebo had type 2 diabetes (hazard ratio 0.12; 95% CI, 0.1 to 0.2; P<0.001) ^[1]. How much weight participants regained during those 17 weeks has not been reported in these documents.

On side effects, the journal reported that apart from COVID-19, the most common adverse events were gastrointestinal, most were mild to moderate, and they occurred mainly during dose escalation in the first 20 weeks. No new safety signals were identified ^[1]. Lilly listed nausea, diarrhea and constipation as the most common gastrointestinal side effects ^[2]. A post hoc mediation analysis suggested about half of the effect on delaying type 2 diabetes was associated with medication-induced weight loss, with the rest potentially tied to other effects of the drug ^[2].

Why it matters for patients

Prediabetes is a common reason people are offered a GLP-1 or dual-agonist medicine, and this is the longest completed trial of tirzepatide reported so far ^[2]. The absolute difference in this study is large: about 13 in 100 placebo participants developed diabetes over roughly three and a half years, compared with about 1 in 100 treated participants ^[1]. The number needed to treat of nine describes a group, not any one person's odds, and it applies to adults who have both obesity and prediabetes, the group studied here ^[1][2]. Tirzepatide is approved in the U.S. as Mounjaro for type 2 diabetes and as Zepbound for weight management, both alongside diet and exercise ^[2]. Whether regulators will add a diabetes-prevention indication has not been reported. The trial was funded by Eli Lilly, and several listed authors are Lilly employees ^[1].

What happens next

The journal published the article online on November 13, 2024, and in its print issue on March 6, 2025 ^[1]. Lilly said it submitted tirzepatide data for moderate-to-severe obstructive sleep apnea and obesity to the FDA and other regulators in 2024 and planned to submit heart failure with preserved ejection fraction data later that year ^[2]. Outcomes beyond 193 weeks, and any effect on diabetes risk after treatment stops for a longer period, have not been reported.