Tirzepatide for Prediabetes: The SURMOUNT-1 Three-Year Data
Prediabetes is the most common diagnosis nobody treats. It is a lab finding, it produces no symptoms, and the conventional advice — lose weight, exercise — is right and rarely enough on its own. More than a third of American adults have it; most do not know.
Tirzepatide has the longest and clearest trial evidence of any GLP-1 medication for stopping prediabetes becoming diabetes. This page is about that evidence and the patient it applies to. The metformin page on the same question covers the older, cheaper, gentler option.
What "prediabetes" actually means
Three measurements define it: an HbA1c between 5.7 and 6.4%, a fasting glucose between 100 and 125 mg/dL, or a two-hour glucose on a tolerance test between 140 and 199 mg/dL. Any one is enough. Our explainers on A1c, fasting insulin and HOMA-IR cover what each number is telling you.
Underneath the label is a process — insulin resistance — that usually started years earlier and that a fasting glucose is slow to reveal. That is why we draw fasting insulin alongside glucose: it rises first. Prediabetes is a late name for an early problem.
Left alone, roughly one in four people with prediabetes progress to type 2 diabetes within five years, and the cardiovascular risk starts rising before the diagnosis changes.
What SURMOUNT-1 found over three years
SURMOUNT-1 was tirzepatide's main obesity trial. Within it, 1,032 participants had prediabetes at the start, and that group was kept on treatment or placebo for 176 weeks — nearly three and a half years — specifically to see whether they developed diabetes.
Over that period, tirzepatide reduced progression to type 2 diabetes by 94% compared with placebo. Weight loss at three years ranged from about 15% to 23% depending on the arm, against 2% on placebo. The result was published in the New England Journal of Medicine in November 2024.
That is the most durable diabetes-prevention result any weight-loss medication has produced. It is roughly three times the relative reduction metformin achieved in the Diabetes Prevention Program, and it held for three years rather than three.
What happened when it stopped
The trial then did something unusual and useful: it took everyone off the medication for 17 weeks and kept watching.
Participants began to regain weight, and some progressed to diabetes. The risk reduction versus placebo fell from 94% to 88%. Two readings of that are both true. The protection did not vanish the day the drug stopped — most of the benefit was still there four months later. And the direction was clear: the benefit is a consequence of the weight and metabolic change, and both begin to reverse without the medication.
We say this plainly because the alternative is a patient who stops at eighteen months, regains, and concludes the treatment failed. It did not fail. It was a treatment for an ongoing condition, and it was stopped. What happens after is on the main page under "what happens if you stop."
Who this is for
The patient this page describes is over 45, carries weight — a BMI of 27 or more with the prediabetes counting as the weight-related condition, or 30 or more regardless — and has a prediabetic A1c or fasting glucose, often with a raised fasting insulin that has been climbing for years. Frequently there is a family history of type 2 diabetes. Sometimes a CGM has already shown post-meal excursions that a fasting draw missed.
For that patient, tirzepatide is not a weight-loss drug that happens to help glucose. It is a treatment for the process underneath both, with three-year evidence behind it.
It is not for someone with a normal A1c and a normal fasting insulin who wants to lose weight for other reasons — that is a different conversation on the main page. And it is not for type 2 diabetes that has already been diagnosed: that is managed by whoever manages your diabetes, and Mounjaro's diabetes indication belongs in that setting.
Where metformin fits
Metformin has been the default drug for prediabetes for twenty years, and for a good reason: it is safe, cheap, and reduced progression by about a third in the Diabetes Prevention Program. For someone with a modest weight problem, a mild A1c elevation and a preference for the lightest intervention, it remains a reasonable first choice, and we prescribe it.
Tirzepatide is the choice when weight is the main driver, when the numbers are moving in the wrong direction despite effort, or when the metabolic picture is advanced enough that a one-third reduction is not the target. The metformin prediabetes page makes the case from the other side.
Frequently asked questions
In SURMOUNT-1, adults with prediabetes and obesity on tirzepatide were 94% less likely to progress to type 2 diabetes over three years than those on placebo.
Prediabetes counts as a weight-related condition for the obesity indication in adults with a BMI of 27 or above. Eligibility is a clinical decision made on your labs and history.
It began to in the trial. Four months after stopping, the risk reduction had fallen from 94% to 88% and weight was returning. The condition is ongoing; so is the treatment decision.
It produced a much larger reduction in progression — roughly 94% against metformin's roughly 31% in the Diabetes Prevention Program — with far greater weight loss. Metformin remains the lighter, cheaper option and is the right choice for some people.
A1c, fasting glucose, fasting insulin, lipids including ApoB, liver enzymes and kidney function as a baseline, then A1c and insulin on a schedule. A CGM is sometimes added.
Probably not. The indication and the evidence are both in people with overweight or obesity. Normal-weight prediabetes is worth investigating for other causes first.
Where this fits in your plan
Start with a baseline panel that includes fasting insulin, not just glucose. If the numbers put you in the prediabetic range with weight to lose, the Tirzepatide Injection page covers how the medication is used here.
We measure first. Then we act.
References
- Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. NEJM 2024;392:958–971.
- Eli Lilly. Tirzepatide reduced the risk of developing type 2 diabetes by 94% in adults with pre-diabetes and obesity or overweight. August 2024.
- Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. NEJM 2002;346:393–403.
- American Diabetes Association. Standards of Care in Diabetes — 2026. Section 3: Prevention or Delay of Diabetes.
- CDC. National Diabetes Statistics Report — prediabetes prevalence.
- Back toTirzepatide Injection
- Metformin for prediabetesTwenty years of evidence say metformin cuts progression to diabetes by about a third — and say exactly who benefits most. Where it fits against lifestyle and a GLP-1.Read
- HOMA-IR explainedHOMA-IR combines fasting glucose and fasting insulin into a single index. What it is good for, where it falls down, and why it is better for tracking than diagnosing.Read
How we write and review our content
ACT 2 Health provides clinician-led care. Treatments are available only to eligible patients following clinical evaluation and within applicable regulations. This content is educational and is not medical advice. Individual results vary.
Diagnostic testing does not diagnose or rule out disease on its own and is interpreted by a licensed provider alongside your history and examination.
All medical decisions are made solely by licensed healthcare professionals. Medications are prescribed only when medically necessary. GLP-1 medications are not suitable for everyone. Results may vary.
Compounded medication. Prepared by a licensed compounding pharmacy under a prescription written for you. Compounded medications are not FDA-approved, are not reviewed by the FDA for safety or effectiveness, and are not equivalent to or interchangeable with any branded product. Prescribed only when a licensed provider determines it is medically appropriate.
Care is delivered via telemedicine by healthcare professionals licensed in the state where the patient is located. Services are available only in states where our providers are licensed.