In the trials, most people with prediabetes who took a GLP-1 medication ended up with normal blood sugar again, and far fewer of them went on to develop type 2 diabetes.
That's the headline, and it holds up. The published data also follows those same people after they came off the medication, and those numbers look different enough that you'd want them before you decide anything.
The Quick Answer
- In STEP 10, a trial of adults with obesity and prediabetes, 81% of the semaglutide group had normal blood sugar at 52 weeks, compared with 14% of the group doing diet and activity counseling alone.1
- In the three-year SURMOUNT-1 study, 1.3% of participants on tirzepatide were diagnosed with type 2 diabetes over 176 weeks, versus 13.3% on placebo.2 That works out to a 94% lower risk, and roughly nine people treated to prevent one case.3
- The effect fades when treatment stops. In STEP 10, 44% of the semaglutide group still had normal blood sugar 28 weeks after coming off it, down from 81%.1
- No GLP-1 is FDA-approved for prediabetes. Semaglutide and tirzepatide are approved for chronic weight management and for type 2 diabetes. Using one with prediabetes in mind is a weight and risk conversation with a provider, not a labeled indication.
- Weight loss appears to be doing much of the work, so the lifestyle side of this matters as much as the prescription.
- What prediabetes actually means
- What the GLP-1 trials found
- How much is the drug and how much is the weight loss
- What happens when you stop
- Nobody is approved for this yet
- Lifestyle still moves the numbers
- Who this conversation is actually for
- How we approach it at Defiant
- Key Takeaways
- Frequently Asked Questions
What Prediabetes Actually Means
Prediabetes is a blood sugar level that's above normal but below the threshold for type 2 diabetes. In practice it means one of three lab findings: an A1c between 5.7% and 6.4%, a fasting glucose between 100 and 125 mg/dL, or a two-hour glucose between 140 and 199 mg/dL on an oral glucose tolerance test.
It's remarkably common, and most people who have it don't know. The CDC puts the number at 115.2 million American adults, more than two in five, and says 8 in 10 of them are unaware.6 Prediabetes has no symptoms, so you either find out from a lab draw or you don't find out.
The label also tends to get waved off once you do have it. A lot of people leave a physical having been told their A1c is "a little high, let's watch it," and then nothing changes for three years. Elevated glucose in that range is itself associated with increased cardiovascular risk, separate from whatever happens with diabetes later.
What the GLP-1 Trials Found
STEP 10 is the trial built specifically for this question, and it's the one to start with. Researchers enrolled 207 adults with obesity and prediabetes, randomized them 2:1 to weekly semaglutide 2.4 mg or placebo, and gave both groups diet and physical activity counseling for 52 weeks. At the end, 81% of the semaglutide group had returned to normal blood sugar compared with 14% of the placebo group, and average weight loss was 13.9% versus 2.7%.1 The trial also reported that nobody who lost 5% or more of their body weight progressed to type 2 diabetes over those 52 weeks, in either group.1
SURMOUNT-1 ran the longest. The 1,032 participants who had prediabetes at enrollment stayed on tirzepatide or placebo for 176 weeks, which is about three and a half years. By the end, 1.3% of the tirzepatide group had been diagnosed with type 2 diabetes compared with 13.3% of the placebo group, a hazard ratio of 0.07.23 Average weight loss on the 15 mg dose was 19.7% at 176 weeks.2
The STEP program analysis pooled 3,375 adults across STEP 1, 3, and 4 and looked at the 1,536 who had prediabetes at baseline. After 68 weeks, the share who had returned to normal blood sugar was 84.1% on semaglutide versus 47.8% on placebo in STEP 1, with similar gaps in the other two trials.4
| STEP 101 | SURMOUNT-1, 3-year23 | STEP program pooled4 | |
|---|---|---|---|
| Medication | Semaglutide 2.4 mg | Tirzepatide 5, 10, 15 mg | Semaglutide 2.4 mg |
| Who | Obesity + prediabetes | Obesity or overweight + prediabetes | Overweight/obesity, prediabetes subgroup |
| Participants | 207 | 1,032 | 1,536 with prediabetes |
| Length | 52 weeks | 176 weeks | 68 weeks |
| Normal blood sugar at end | 81% vs 14% | Not the primary endpoint | 84.1% vs 47.8% (STEP 1) |
| Diagnosed with type 2 diabetes | Fewer on semaglutide at 52 and 80 weeks | 1.3% vs 13.3% | Not reported |
| Average weight change | −13.9% vs −2.7% | −19.7% on 15 mg | −14.9% vs −2.4% (STEP 1)7 |
Across both compounds and all three designs, the effect is large and consistent.
How Much Is the Drug and How Much Is the Weight Loss
Researchers ran a mediation analysis on the SURMOUNT-1 data to try to answer exactly this. About half of the delay in diabetes onset was attributable to the weight reduction itself, with the rest potentially coming from other effects of the medication.3
If roughly half the effect travels with the weight loss, then a meaningful share of it may be available to anyone who loses weight, by whatever route gets them there. That makes the eating and training side of a program load-bearing. If about half the benefit rides on the weight loss itself, how you get there matters.
That reading fits the 5% finding from STEP 10, where weight loss that modest was enough to keep people out of the diabetes column over a year, in the placebo group as much as the treatment group.1
What Happens When You Stop
STEP 10 kept following participants for 28 weeks after they came off treatment, and the glucose numbers tracked the weight back up. About 6% of original body weight returned in the semaglutide group. Normal blood sugar held in 44% of them at week 80, down from 81% at week 52, against 18% of the placebo group.1 Better than the comparison group and clearly worse than it had been on treatment.
SURMOUNT-1 showed the same pattern on a shorter runway. After a 17-week off-treatment period, type 2 diabetes diagnoses in the tirzepatide group went from 1.3% to 2.4%, and the hazard ratio moved from 0.07 to 0.12.3
Both patterns point the same direction: the research to date shows these medications helping while they're being taken, with the benefit eroding once they stop. Anyone framing a GLP-1 as a short course that permanently resets your metabolism is going past what the published data supports. We'd rather you hear that from us before you start than discover it eight months in.
Nobody Is Approved for This Yet
Semaglutide and tirzepatide are FDA-approved for chronic weight management in adults with obesity, or with overweight plus at least one weight-related condition, and separately for type 2 diabetes. Prediabetes by itself is not an approved indication for either one.
Metformin isn't approved for prediabetes either, for what it's worth, and it has been prescribed that way for decades on the strength of the Diabetes Prevention Program.
So the practical question in a consult comes down to whether you meet the criteria for weight management treatment, with prediabetes sitting in the file as one of the risk factors that adds urgency to the conversation. The specifics on those criteria are in our guide to who qualifies for a GLP-1 program.
Lifestyle Still Moves the Numbers
The Diabetes Prevention Program randomized 3,234 adults with elevated glucose to placebo, metformin, or an intensive lifestyle program targeting 7% weight loss and 150 minutes of activity a week. Over an average of 2.8 years, the lifestyle arm cut new diabetes cases by 58% while metformin cut them by 31%, which put the lifestyle program ahead of the drug.5
The same effect shows up in the control groups of the GLP-1 trials. In the pooled STEP analysis, 47.8% of the STEP 1 placebo group returned to normal blood sugar on lifestyle intervention alone.4 In STEP 10, where both groups got nine sessions with a dietitian, 14% of placebo participants did.1
Nine dietitian sessions is a real program, and more structured support than most people get from a primary care relationship. A trial result reflects that kind of support, which a 15-minute annual physical does not provide.
Who This Conversation Is Actually For
A lot of the people who bring us a prediabetes reading have been watching an A1c drift up for years, 5.7 to 5.9 to 6.1, with a doctor telling them each time to eat better. They've already tried eating better. Nobody has been tracking whether it's working at a resolution finer than once a year, which makes it hard to know whether the last twelve months of effort did anything.
Others are reacting to family history. A parent with type 2 diabetes changes how you read your own labs, and the number stops looking like a warning and starts looking like a schedule.
Then there are the people who found out sideways, through a work biometric screening or a life insurance panel, and aren't sure whether it counts as a real problem. It's worth acting on, and it's also among the more responsive findings you'll get back from a lab, which is a decent position to be in.
How We Approach It at Defiant
Prediabetes shapes the medical weight loss conversation here rather than running as its own service, since there's no such thing as a prediabetes prescription.
A consult starts with labs. We write the order and you get drawn at your primary care office or through Rythm Health, since we don't draw blood in-clinic. For someone in this situation, the A1c and fasting glucose are the numbers that frame everything else.
From there it's a Styku 3D body scan to set a baseline, a provider visit to work out whether medication fits your situation, and monthly scans after that. Body composition gives a fuller read on your progress than scale weight alone, which is why we track it, and we get into that in body composition on a GLP-1.
If medication is part of it, our Custom GLP-1 Protocol starts at $295 a month and includes the medication, provider oversight, bi-weekly titration check-ins, monthly body composition scans, and nurse access between visits. The bi-weekly cadence is the piece that separates this from a telehealth subscription, since it lets us adjust when side effects show up instead of waiting a month to hear about them.
We're at 5100 Lincoln Ave in Lisle, serving Naperville, Downers Grove, Wheaton, Bolingbrook, and the rest of Chicago's western suburbs.
- In STEP 10, 81% of adults with obesity and prediabetes returned to normal blood sugar on semaglutide 2.4 mg at 52 weeks, versus 14% on lifestyle counseling alone.
- Over three years in SURMOUNT-1, 1.3% of the tirzepatide group developed type 2 diabetes compared with 13.3% of the placebo group, a 94% lower risk.
- The benefit is tied to staying on treatment. Normal blood sugar held in 44% of the STEP 10 semaglutide group 28 weeks after stopping, down from 81%.
- About half the diabetes-prevention effect in SURMOUNT-1 was attributable to weight loss itself, which is why the nutrition and training side isn't optional.
- No GLP-1 is FDA-approved for prediabetes. Eligibility runs through the weight management criteria, with prediabetes as a risk factor in the file.
- Intensive lifestyle intervention cut diabetes risk 58% in the Diabetes Prevention Program, outperforming metformin's 31%.
Frequently Asked Questions
Get Ahead of the Number.
A prediabetes reading is a number you can work on. A consult starts with your labs and a body composition scan, and ends with a plan built around what they show.
Keep Reading
Last updated September 19, 2026.
References
- McGowan BM, Bruun JM, Capehorn M, et al; STEP 10 Study Group. Efficacy and safety of once-weekly semaglutide 2.4 mg versus placebo in people with obesity and prediabetes (STEP 10). Lancet Diabetes Endocrinol. 2024;12(9):631-642. PubMed
- Jastreboff AM, le Roux CW, Stefanski A, et al; SURMOUNT-1 Investigators. Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med. 2025;392(10):958-971. PubMed
- Eli Lilly and Company. Treatment with tirzepatide in adults with pre-diabetes and obesity or overweight resulted in sustained weight loss and nearly 99% remained diabetes-free at 176 weeks. November 2024. Lilly
- Perreault L, Davies M, Frias JP, et al. Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. Diabetes Care. 2022;45(10):2396-2405. PubMed
- Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. N Engl J Med. 2002;346(6):393-403. PubMed
- Centers for Disease Control and Prevention. Prediabetes: Could It Be You? Last reviewed February 2026. CDC
- Wilding JPH, Batterham RL, Calanna S, et al; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. PubMed