Tirzepatide and Prediabetes: What Three Years of SURMOUNT-1 Data Show About Preventing Type 2 Diabetes

Prediabetes rarely causes symptoms, and the only clue is often a lab value sitting in a gray zone that, for many adults with obesity, marks the road toward type 2 diabetes.

The question patients bring to a telehealth visit is a reasonable one: if tirzepatide lowers both weight and blood sugar, can it keep prediabetes from turning into diabetes? The strongest evidence so far comes from a three year analysis of the SURMOUNT-1 trial, and the result is striking but has limits worth understanding.

What is prediabetes, and how is it diagnosed?

Prediabetes is a blood sugar level that is higher than normal but still below the threshold for type 2 diabetes. The CDC lists three standard tests that can identify it, and a result in the prediabetes range on any one of them can flag the condition.

Underneath the lab value, prediabetes usually reflects insulin resistance, in which cells respond less to insulin and the pancreas must release more of it, and excess body weight is one of the strongest drivers of that resistance.

How common is prediabetes in the United States?

Prediabetes is extremely common. The CDC's National Diabetes Statistics Report estimates that 115.2 million US adults have prediabetes, and among people aged 65 or older the estimate is 31.3 million, or 52.1% of that age group. Because it causes no symptoms, it is often found on a routine metabolic panel.

Can tirzepatide prevent type 2 diabetes in people with prediabetes?

In clinical trials, tirzepatide sharply reduced the number of people with obesity and prediabetes who progressed to type 2 diabetes. The key evidence comes from the SURMOUNT-1 analysis by Jastreboff and colleagues, published in the New England Journal of Medicine in 2025.

SURMOUNT-1 enrolled 2539 adults with obesity, of whom 1032 also had prediabetes. That group remained on its assigned treatment, which was tirzepatide 5 mg, 10 mg or 15 mg once weekly or placebo, for 176 weeks and was then followed for a 17 week period off treatment. Over the 176 weeks, 1.3% of participants in the tirzepatide groups received a type 2 diabetes diagnosis, compared with 13.3% in the placebo group, for a hazard ratio of 0.07.

Two caveats belong next to that result. Every participant was also counseled on a reduced calorie diet and physical activity, so the trial tested tirzepatide on top of lifestyle advice rather than in place of it. The trial was also funded by Eli Lilly, the manufacturer, so independent long term data will still matter.

How much weight did people with prediabetes lose over three years?

Weight loss in the prediabetes group was large and largely sustained. At 176 weeks, mean body weight fell by 12.3% on the 5 mg dose, 18.7% on 10 mg and 19.7% on 15 mg, compared with 1.3% on placebo.

Weight loss of that size matters for prediabetes because it eases the insulin resistance that pushes blood sugar upward. Tirzepatide also acts on glucose directly through GIP and GLP-1 signaling, and the trial was not designed to separate the two effects.

What happens to diabetes risk if tirzepatide is stopped?

Some of the protection faded once treatment ended. After the 17 week period off treatment, 2.4% of people who had received tirzepatide had type 2 diabetes, compared with 13.7% of those who had received placebo, for a hazard ratio of 0.12.

The tirzepatide group still fared far better than placebo, yet the share with diabetes nearly doubled within a few months of stopping, so a long term plan, including what happens if the medication is paused, is worth discussing with the prescribing clinician from the start.

How does tirzepatide compare with lifestyle change and metformin?

The benchmark for diabetes prevention remains the Diabetes Prevention Program (DPP), reported by Knowler and colleagues in the New England Journal of Medicine in 2002. The DPP randomized 3234 people with elevated blood sugar to placebo, metformin 850 mg twice daily, or an intensive lifestyle program aiming for at least 7% weight loss and 150 minutes of physical activity per week.

Over an average follow up of 2.8 years, diabetes incidence was 11.0 cases per 100 person years on placebo, 7.8 on metformin and 4.8 with the lifestyle program, which means lifestyle change cut incidence by 58% and metformin by 31%.

These trials cannot be compared head to head because they enrolled different populations decades apart, but the DPP does establish lifestyle change as a proven prevention tool, and SURMOUNT-1 studied tirzepatide as an addition to it.

Does tirzepatide return blood sugar to normal, or only delay diabetes?

For many trial participants, blood sugar returned to the normal range. A post hoc analysis of the SURMOUNT-5 trial by Galindo and colleagues, published in the Journal of Endocrinological Investigation in 2026, examined 425 participants with obesity and prediabetes who received either tirzepatide or semaglutide at the maximum tolerated dose.

The researchers defined normal blood sugar as an HbA1c below 5.7% together with a fasting glucose below 100 mg/dL. At week 72, 89.9% of tirzepatide participants met that definition, compared with 76.2% of semaglutide participants, while mean HbA1c fell by 0.60% and 0.48% and mean body weight fell by 21.5% and 14.5%, respectively.

Post hoc analyses generate signals rather than settled conclusions, and participants here started with a mean HbA1c of 5.86%, near the lower edge of the prediabetes range.

Who with prediabetes is most likely to progress to diabetes?

Risk varies within prediabetes, and a 2026 SURMOUNT-1 post hoc analysis in the Journal of the Endocrine Society (doi.org/10.1210/jendso/bvag190) explored which lab criteria best predicted progression and found that a one hour glucose tolerance result of 155 mg/dL or higher identified most future cases in the placebo group, with a sensitivity of 0.83.

The same analysis reported that tirzepatide was associated with a 90% to 99% reduction in new onset type 2 diabetes in higher risk groups, compared with 68% to 91% in standard risk groups, depending on the criterion used. As a manufacturer sponsored post hoc analysis, it is best read as a guide for future research.

Is tirzepatide approved to treat prediabetes?

Tirzepatide is not approved specifically for prediabetes. According to the current Zepbound prescribing information (DailyMed), Zepbound is indicated, together with a reduced calorie diet and increased physical activity, to reduce excess body weight and maintain that reduction long term in adults with obesity or in adults with overweight and at least one weight related condition, and to treat moderate to severe obstructive sleep apnea in adults with obesity.

Prediabetes can be one of the weight related conditions a clinician weighs when assessing eligibility, but diabetes prevention is not a separate labeled indication. The labeled dosing starts at 2.5 mg once weekly for 4 weeks and then increases in steps toward a maintenance dose of 5 mg, 10 mg or 15 mg, based on response and tolerability.

What side effects appeared in the three year trial?

Apart from COVID, which circulated during the study period, the most common adverse events were gastrointestinal, most were mild to moderate, and they occurred mainly during dose escalation in the first 20 weeks, with the investigators reporting no new safety signals. The Zepbound label also carries a boxed warning based on thyroid C-cell tumors seen in rats, which is one reason a full medical history review is part of every responsible prescribing decision.

The bottom line

The SURMOUNT-1 three year data are among the strongest results reported so far for preventing type 2 diabetes in people with obesity and prediabetes, with new diagnoses falling from 13.3% on placebo to 1.3% on tirzepatide during treatment alongside weight loss of up to about 20%. Part of that protection was lost within months of stopping, which frames tirzepatide as a long term management tool rather than a one time fix. Lifestyle change remains the foundation, and the decision to add medication belongs in a conversation with a licensed clinician who knows the patient's full history.