Can GLP-1 Drugs Prevent Type 2 Diabetes?

Prediabetes affects an enormous number of people — according to the CDC, more than 2 in 5 adults in the United States, and hundreds of millions more worldwide. Most receive lifestyle advice and monitoring. Very few receive medication specifically aimed at stopping progression to type 2 diabetes.

Data from the 3-year part of the SURMOUNT-1 clinical trial adds important evidence to that conversation.

Understanding prediabetes: why it matters

Prediabetes is defined by blood sugar levels that are elevated above normal but not yet high enough to meet the diagnostic threshold for type 2 diabetes. It is diagnosed using:

• Fasting plasma glucose: 100–125 mg/dL (5.6–6.9 mmol/L)
• HbA1c: 5.7–6.4%
• 2-hour glucose tolerance test: 140–199 mg/dL

The condition is often silent. Many people with prediabetes have no symptoms and are unaware of their diagnosis. But without intervention, the trajectory is concerning:

• Without changes, many people with prediabetes go on to develop type 2 diabetes; in the Diabetes Prevention Program's placebo group, about 11 in 100 people developed diabetes each year
• Cardiovascular risk increases even before the diabetes threshold is crossed
• Complications including kidney disease and nerve damage can begin developing during the prediabetes phase

Insulin resistance is the core mechanism. The body's cells do not respond normally to insulin, forcing the pancreas to work harder. Over time, the pancreatic beta cells that produce insulin become exhausted — and blood sugar control deteriorates further.

The earlier this process is interrupted, the better the long-term outcome.

What is the SURMOUNT-1 trial?

SURMOUNT-1 was Eli Lilly's pivotal Phase 3 clinical trial for tirzepatide as a weight management drug. It enrolled 2,539 adults with obesity and no diabetes, and ran for 72 weeks.

The main trial results, published in the New England Journal of Medicine in 2022, showed substantial weight loss at 72 weeks:

• Average 20.9% body weight loss at the 15 mg dose (versus 3.1% with placebo)
• 57% of participants on 15 mg achieved 20% or more weight loss

But the story of prediabetes prevention came from a specific subset of participants and an extension of the trial timeline.

What the 3-year extension found

Of the 2,539 SURMOUNT-1 participants, 1,032 had prediabetes at the start of the trial. This group continued their assigned treatment for 176 weeks (approximately 3.4 years), followed by 17 weeks off treatment, to measure whether tirzepatide could delay progression to type 2 diabetes.

Lilly announced headline results in August 2024, and the full results were published in the New England Journal of Medicine (online November 2024).

The headline finding:

Over 176 weeks, the risk of progressing from prediabetes to type 2 diabetes was about 93-94% lower with tirzepatide than with placebo (hazard ratio 0.07; Lilly reported this as a 94% reduction).

This is a large effect in a trial of people with obesity and prediabetes.

Full results by dose

In absolute terms: 1.3% of tirzepatide participants developed type 2 diabetes during the trial, compared to 13.3% in the placebo group.

After 17 weeks off treatment, 2.4% of the tirzepatide group and 13.7% of the placebo group had type 2 diabetes (hazard ratio 0.12, about 88% lower risk). This suggests some protection persisted briefly, but that continued treatment may be needed to maintain the benefit.

Putting this in context: how does it compare to other options?

The Diabetes Prevention Program (DPP)

The DPP, the landmark 1990s US trial that established the gold standard for prediabetes management, showed:

• Lifestyle intervention (diet + exercise): 58% risk reduction over 3 years
• Metformin: 31% risk reduction over 3 years

Tirzepatide's risk reduction in SURMOUNT-1 was larger than the DPP results, but these were different trials, in different people, decades apart, so the figures cannot be compared directly. Lifestyle changes clearly work. Tirzepatide produces more weight loss than most lifestyle programmes achieve, which is likely a large part of its effect.

Why does this comparison matter?

The DPP lifestyle programme requires intensive coaching, sustained dietary change, and regular exercise at a level most people do not maintain long-term. In real-world settings, the benefit is smaller than in clinical trials. Metformin is inexpensive and widely used, but its risk reduction is modest.

For high-risk individuals — those with prediabetes, obesity, and other metabolic risk factors — tirzepatide may offer a substantially more effective pharmacological option than anything previously available.

Why does tirzepatide have such a large effect on diabetes risk?

The mechanism works on several levels simultaneously.

Weight loss reduces insulin resistance at its root

Visceral fat — the fat stored around the organs in the abdomen — is a major driver of insulin resistance. Reducing total body weight by 12–20%, as seen in this trial, substantially reduces visceral fat, allowing cells to respond to insulin normally again. When insulin resistance decreases, the pancreatic beta cells no longer have to overwork — and the progression toward diabetes slows or reverses.

Tirzepatide's dual mechanism adds metabolic benefit beyond weight

Tirzepatide activates both GLP-1 and GIP receptors. GLP-1 activation:

• Stimulates insulin secretion from the pancreas in a glucose-dependent way
• Suppresses glucagon (which raises blood sugar)
• Slows gastric emptying, smoothing post-meal glucose spikes

GIP activation adds:

• Enhanced insulin secretion
• Potential direct effects on fat metabolism and adipose tissue function

Together, these effects give the pancreatic beta cells a chance to recover and function more effectively — which may explain why some participants maintained reduced diabetes risk even briefly after stopping the drug.

Restoration of glycaemic control

As weight falls and insulin resistance improves, fasting glucose and HbA1c can move back into the normal range. Many participants who had prediabetes at baseline returned to normal blood sugar levels during treatment.

What this means for patients with prediabetes

If you have prediabetes and obesity or overweight, this data is relevant to your situation and worth discussing with your doctor, alongside lifestyle support and other options.

Questions to raise at your next appointment

• What is my current HbA1c trend? Is it moving upward over time?
• Given my weight and prediabetes status, would tirzepatide or semaglutide be appropriate?
• What lifestyle changes should accompany any medication?
• Is there insurance coverage for this use, or are self-pay options viable?
• How long should I continue before reassessing?

Setting realistic expectations

The trial used tirzepatide at 5 mg, 10 mg, and 15 mg. The diabetes result was pooled across doses, meaning even the lower 5 mg dose contributed. Average weight loss at 176 weeks was 12–20% depending on dose. Expecting diabetes prevention without meaningful weight loss is unrealistic.

Safety

The most common side effects in the trial were digestive (nausea, diarrhoea, constipation, vomiting), mostly mild to moderate and mainly during the first 20 weeks of dose increases.

Get urgent medical help for severe stomach pain that does not go away (it may spread to your back, with or without vomiting), pain in the upper right abdomen with fever or yellowing of the skin or eyes, signs of a serious allergic reaction (swelling of the face, lips or throat, trouble breathing), or vomiting or diarrhoea so severe you cannot keep fluids down. If you also take insulin or a sulfonylurea, know the signs of low blood sugar, as your doses of those medicines may need adjusting. Tell your doctor about any vision changes if you have diabetic eye disease, and tell the team before any surgery or sedation. Tirzepatide carries a US boxed warning about thyroid C-cell tumours and must not be used if you or a close relative has had medullary thyroid carcinoma (MTC) or if you have MEN 2. If you use the contraceptive pill, tirzepatide can make it less reliable: the label advises switching to a non-oral method or adding a barrier method for 4 weeks after starting and for 4 weeks after each dose increase.

The drug does the heavy lifting pharmacologically, but supporting it with better food choices, adequate hydration, sleep, and movement amplifies the benefit.

What about semaglutide (Ozempic/Wegovy)?

Semaglutide has not been studied in a dedicated 3-year prediabetes prevention trial. But the evidence for diabetes risk reduction is growing:

• The SELECT cardiovascular outcomes trial (NEJM 2023, n=17,604) in people with overweight or obesity and cardiovascular disease, without diabetes, also reported improvements in blood sugar measures with semaglutide
• Sub-analyses from semaglutide weight-loss trials show HbA1c and fasting glucose reductions in people with prediabetes at baseline

The biological rationale is the same as for tirzepatide — GLP-1 activation, weight loss, and insulin sensitivity improvement — though the dual GIP/GLP-1 mechanism of tirzepatide may offer additional benefit.

Tracking prediabetes markers on GLP-1 therapy

If you are on GLP-1 therapy and have prediabetes, your regular blood tests tell the story beyond weight loss.

Key markers to track:

These are the American Diabetes Association cut-offs used in the US; your lab's ranges and local guidelines may differ. Check HbA1c and fasting glucose as often as your doctor advises while on GLP-1 therapy. A consistent downward trend confirms the medication is working metabolically — not just on the scale.

Keeping a systematic log of your medication history, dose changes, and these blood results makes it far easier to correlate changes and communicate progress to your doctor.

Final takeaway

In the 3-year part of the SURMOUNT-1 trial, people with obesity and prediabetes on tirzepatide had a much lower risk of developing type 2 diabetes than those on placebo (1.3% versus 13.3%).

Using GLP-1 drugs only to prevent diabetes is currently off-label. But the data warrants a conversation with your doctor, especially if you have prediabetes alongside overweight or obesity.

Consult your healthcare provider before starting any medication.

Sources

• Jastreboff AM et al. Tirzepatide for Obesity Treatment and Diabetes Prevention (SURMOUNT-1, 3-year results). N Engl J Med. 2025;392:958-971: https://pubmed.ncbi.nlm.nih.gov/39536238/
• Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022: https://pubmed.ncbi.nlm.nih.gov/35658024/
• Knowler WC et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin (Diabetes Prevention Program). N Engl J Med. 2002;346:393-403: https://pubmed.ncbi.nlm.nih.gov/11832527/
• CDC — prediabetes and preventing type 2 diabetes: https://www.cdc.gov/diabetes/prevention-type-2/prediabetes-prevent-type-2.html
• Mounjaro US prescribing information (Eli Lilly, revised August 2026): https://pi.lilly.com/us/mounjaro-uspi.pdf
• Zepbound US prescribing information (Eli Lilly, revised August 2026): https://pi.lilly.com/us/zepbound-uspi.pdf
• MedlinePlus — tirzepatide injection: https://medlineplus.gov/druginfo/meds/a622044.html
• Lincoff AM et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 2023;389:2221-2232

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