SURMOUNT-2: Tirzepatide When You Also Have Diabetes
Last verified May 2026 · 3 · Finished; headline results published 2023 · NCT04657003 ↗
Weight loss on GLP-1 drugs is consistently smaller in people with type 2 diabetes, across every drug in the class and by a fairly stable margin. The mechanisms are debated — differences in insulin, in glucose handling, in concomitant medication — but the pattern is robust enough to expect. SURMOUNT-2 quantifies it for tirzepatide with the same protocol structure as SURMOUNT-1, which makes this the clean version of that comparison rather than an inference across unrelated trials.
- Enrollment
- 938
- Duration
- 72 weeks on treatment, the first 20 spent raising the dose, then 4 weeks of safety follow-up
- Drug
- Tirzepatide
- Population
- Adults 18 and over with a BMI of 27 or more, type 2 diabetes with an HbA1c between 7% and 10%, and a diabetes regimen that had been stable for at least three months — diet and exercise, or up to three oral drugs. ⚠ Insulin users were excluded, which matters for reading the low-blood-sugar figures below. Average starting weight 100.7 kg at a BMI of 36.1, average HbA1c 8.02%, average age 54.2, half women, and about 8.5 years since diagnosis. 60% of participants were Hispanic or Latino.
Primary endpoint
How much body weight came off over 72 weeks, at each dose
Treatment arm
10 mg: -12.8% (SE 0.6); 15 mg: -14.7% (SE 0.5)
Comparator
-3.2% (SE 0.5)
Treatment difference: Placebo-subtracted -9.6 percentage points at 10 mg (95% CI -11.1 to -8.1) and -11.6 percentage points at 15 mg (95% CI -13.0 to -10.1); P<0.0001 for both
★ Put this next to the trial in people without diabetes and the correction is six percentage points — 14.7% here against 20.9% there, same drug, same top dose, near-identical protocol. If you have diabetes, this is the number the marketing should be quoting at you and generally is not.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Lost at least 5% of body weight More than four in five got there despite diabetes being in the picture. | 10 mg: 81.6%; 15 mg: 86.4% | 30.6% | Odds ratio favored both tirzepatide doses; P<0.0001 |
| Lost at least a tenth of body weight About two thirds on either dose — the level at which fatty liver tends to regress and metabolic markers move meaningfully. | 10 mg: 63.4%; 15 mg: 69.6% | 8.7% | P<0.0001 for both doses |
| Lost at least 15% ★ Over half the top-dose group, with diabetes on board. That is territory that used to require an operation. | 10 mg: 41.4%; 15 mg: 51.8% | 2.6% | P<0.0001 for both doses |
| Lost at least a fifth ⚠ A third at the top dose here, against more than half in the non-diabetic trial. The diabetes penalty is widest at the ambitious end. | 10 mg: 23.0%; 15 mg: 34.0% | 1.0% | P<0.0001 for both doses |
| Three-month average blood sugar ★ The largest blood-sugar reduction any phase 3 trial in this population has reported — from an average of 8.02% into the mid-5s. If your goal is diabetes control as much as weight, this row is the argument. | 10 mg: -2.14; 15 mg: -2.22 | -0.16 | Placebo-subtracted -1.98 percentage points at 10 mg and -2.06 at 15 mg |
| Got blood sugar under the standard 7% target Roughly nine of every ten, set against under three in ten on placebo and lifestyle change. | 10 mg: 90.0%; 15 mg: 90.7% | 29.3% | P<0.0001 for both doses |
| Inches off the waist Close to 14 cm at the top dose — about 5.5 inches — against 3.4 cm on placebo. | 10 mg: -11.2 cm; 15 mg: -13.8 cm | -3.4 cm | Placebo-subtracted -7.8 cm at 10 mg and -10.4 cm at 15 mg |
| Blood sugar after an overnight fast Down about 50 mg/dL, against essentially no change on placebo. | 10 mg: -49.2 mg/dL; 15 mg: -51.7 mg/dL | -2.4 mg/dL | Placebo-subtracted -46.8 mg/dL at 10 mg and -49.3 mg/dL at 15 mg |
| Top blood-pressure number About 6 points beyond placebo, roughly what adding a low-dose blood-pressure tablet achieves. | -7.2 mmHg | -1.0 mmHg | Placebo-subtracted -6.2 mmHg |
| Triglycerides, a blood fat Down nearly 30% against under 6% on placebo. | -28.6% | -5.8% | Placebo-subtracted -22.8 percentage points |
| HDL, the other cholesterol Up about 8%, the direction usually treated as favorable. | +8.2% | +1.1% | — |
| LDL, the cholesterol that drives artery disease ⚠ Worth reading carefully because it is counterintuitive: LDL rose in both arms, and rose less on the drug. Nothing in this class is a substitute for a statin. | +2.7% | +6.3% | — |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Stomach and bowel problems Nausea, diarrhea and vomiting led, they were mostly mild to moderate, and they clustered into the 20 weeks while the dose was climbing. | 10 mg and 15 mg pooled: most-common AE class; nausea, diarrhea, and vomiting predominated | Substantially lower on placebo |
| Stopped the drug over a side effect ★ Under 5% on either dose, close to the placebo rate — notably low given how many people reported stomach trouble. Unpleasant and tolerable are different things. | Under 5% across both tirzepatide arms | Similar low rate on placebo |
| Serious adverse events of any kind Broadly similar across all three arms with nothing clustering in one body system. | 10 mg: 5.8% (18/312); 15 mg: 8.7% (27/311) | 7.3% (23/315) |
| Pancreatitis, confirmed by independent review Two cases at the top dose and none elsewhere. ⚠ Two events is too few to draw a conclusion from, and it is the risk this class has always been watched for. | 10 mg: 0 events; 15 mg: 2 events | 0 events |
| Gallbladder problems Balanced between the arms here. Gallstones generally track how fast weight comes off rather than the drug itself. | 15 mg: 2 events | 2 events |
| Blood sugar dropping dangerously low ⛔ Rare in this trial, and the reason is a design choice rather than a property of the drug: nobody on insulin or a sulfonylurea was allowed in. If you take either, this row does not describe you. | Rare across both tirzepatide doses | Rare on placebo |
| Deaths during the trial Two in the 10 mg group, both independently judged unrelated to the drug. | 10 mg: 2; 15 mg: 0 | 0 |
Subgroup analyses
- Where blood sugar started, lower against higher: Weight loss and blood-sugar reduction held across every starting band, with the largest absolute blood-sugar drops in those who started highest
No sign the drug worked differently depending on how poorly controlled the diabetes was.
- Women against men, split almost evenly: Similar relative weight loss in both
★ Women were far better represented here than in the non-diabetic trial, which makes the finding more trustworthy rather than less.
- Region and ethnicity, with 60% of participants Hispanic or Latino: Weight and blood-sugar results broadly consistent wherever people were enrolled
★ Recruitment spanned seven countries on three continents, making this among the most ethnically varied phase 3 trials anywhere in this drug class — an uncommon and real strength.
- What diabetes drugs people were already taking — metformin alone or a combination: Weight and blood-sugar benefits appeared regardless of the existing regimen
⚠ Remember what was not in any regimen here: insulin. Nobody taking it was enrolled.
Clinical significance
If you have type 2 diabetes, this is your trial rather than SURMOUNT-1, and the gap between them is the correction to apply to every headline number you will encounter. It supported extending Zepbound's use toward diabetes-with-obesity populations. ⚠ It is also worth noting what it does not resolve: whether the smaller loss reflects biology or the diabetes medications people were taking alongside, which the trial was not designed to separate.
Who sells tirzepatide, and for how much
This trial tested Tirzepatide. Across the 556 sellers on this register, 253 publish a standing monthly cash price for compounded tirzepatide, from $99 a month, with a median of $240.
⛔ None of those sellers was in this trial. A compounded preparation is not the product studied here: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. The result above is the strongest evidence available for tirzepatide and it was generated on something else. Every seller, with its price record.
Frequently Asked Questions
References
- 1.Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023. PMID: 37385275.
- 2.Eli Lilly and Company. A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight (SURMOUNT-2) — Study Results. ClinicalTrials.gov, NCT04657003. 2024. https://clinicaltrials.gov/study/NCT04657003?tab=results
- 3.U.S. Food and Drug Administration. FDA Approves New Medication for Chronic Weight Management (Zepbound, tirzepatide). FDA Press Announcement, November 8, 2023. 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
- 4.Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021. PMID: 33667417.
- 5.Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021. PMID: 34170647.
- 6.Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022. PMID: 35658024.