Detailed three-year data show 99% of prediabetic patients stayed diabetes-free

Eli Lilly released detailed three-year results from its SURMOUNT-1 trial on Nov. 13, 2024, showing that nearly 99% of adults with prediabetes and obesity or overweight who took tirzepatide had not developed type 2 diabetes after 176 weeks of weekly injections ^[1]. The findings were published in The New England Journal of Medicine and presented at ObesityWeek 2024 ^[1]. Lilly had first disclosed topline results in August ^[2].

Tirzepatide is the active ingredient in Mounjaro, approved for type 2 diabetes, and Zepbound, approved for weight management ^[1]. It is a once-weekly dual GIP and GLP-1 receptor agonist ^[1]. This is the longest completed tirzepatide study to date ^[1].

What the numbers show

SURMOUNT-1 enrolled adults without type 2 diabetes who had obesity, or overweight plus a condition such as high blood pressure, abnormal cholesterol, obstructive sleep apnea or cardiovascular disease ^[1]. The 1,032 participants who had prediabetes at the start stayed enrolled for an extra 104 weeks beyond the original 72-week endpoint ^[1][2]. That gave 762 people on pooled tirzepatide doses (5 mg, 10 mg and 15 mg) and 270 on placebo ^[1].

At week 176, 1.2% of the tirzepatide group had been diagnosed with type 2 diabetes, compared with 12.6% on placebo, using the efficacy estimand — the analysis that looks at results while people stay on treatment ^[1]. Under the treatment-regimen estimand, which counts everyone regardless of whether they stopped the drug, the figures were 1.3% and 13.3% ^[1]. The hazard ratio was 0.06, a 94% reduction in the risk of progressing to diabetes, and the number needed to treat to prevent one case was nine ^[1][2].

Weight loss held up over the three years. Average reductions from baseline at week 176 were 15.4% on 5 mg, 19.9% on 10 mg and 22.9% on 15 mg under the efficacy estimand, versus 2.1% on placebo ^[1]. Under the more conservative treatment-regimen estimand, the numbers were 12.3%, 18.7% and 19.7%, versus 1.3% on placebo ^[1].

Participants were then followed for 17 weeks off treatment, through week 193. By that point, 2.4% of the tirzepatide group had been diagnosed with type 2 diabetes, compared with 13.7% on placebo, and the hazard ratio rose to 0.12 ^[1]. In other words, the gap narrowed somewhat once the drug was stopped, though the tirzepatide group still had far fewer diagnoses.

Lilly also reported sustained improvements in blood sugar control, fasting insulin, blood pressure, lipids and health-related quality of life through 176 weeks ^[1][2]. A post hoc analysis suggested about half of the delay in diabetes onset was linked to weight loss itself, with the rest possibly from other effects of the drug ^[1].

On safety, the profile at 193 weeks was consistent with the earlier 72-week results ^[1]. Other than COVID-19, the most common adverse events were gastrointestinal and generally mild to moderate, most often nausea, diarrhea and constipation ^[1]. Zepbound's labeling also carries a boxed warning about thyroid C-cell tumors, and lists risks including pancreatitis, gallbladder problems, kidney problems from dehydration, and severe allergic reactions ^[1].

Why it matters for patients

Prediabetes is common among people considering GLP-1 and dual-incretin drugs, and the practical question has been whether short-term trial results hold up over years. These data extend the evidence to three years of continuous treatment and show both the weight loss and the diabetes protection were maintained during that period ^[1].

The number needed to treat — nine people treated to prevent one diabetes case over three years — is a useful frame for conversations about benefit versus cost and side effects ^[1][2]. The week-193 data are also worth noting: diagnoses roughly doubled in the tirzepatide group during just 17 weeks off treatment, from 1.2% to 2.4% ^[1]. Lilly framed the results as underscoring "the critical role of long-term therapy," a statement from a company that sells the drug ^[1].

What these data do not show is whether preventing or delaying a diabetes diagnosis translates into fewer heart attacks, kidney failures or deaths. The sources do not report those outcomes. Longer-term studies in chronic kidney disease and in obesity-related illness and death are ongoing ^[1].

What happens next

The FDA was set to decide on tirzepatide for moderate-to-severe obstructive sleep apnea with obesity, following a submission earlier in 2024 ^[1][2]. Lilly said it planned to submit data on heart failure with preserved ejection fraction and obesity to the FDA and other regulators by the end of 2024 ^[1][2]. Tirzepatide was approved as Mounjaro on May 13, 2022, and as Zepbound on Nov. 8, 2023 ^[1].