SURMOUNT-2: Tirzepatide When You Also Have Diabetes

Name: SURMOUNT-2: Tirzepatide When You Also Have Diabetes
Creator: Ruth Calder
Published: 2026-11-07

Last verified November 2026 · Phase 3 · Finished; headline results published 2023 · NCT04657003 ↗

By Ruth Calder · Enforcement Editor

Editorially reviewed. Not medical advice · How we verify contentLast reviewed November 2026

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 measures it for tirzepatide with the same protocol structure as SURMOUNT-1, so the comparison is direct instead of 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 aged 18 or older, BMI at least 27, 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.

The Tirzepatide drug page covers the drug itself: its dosing, cost and side effects.

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, with the same drug, the same top dose and a near-identical protocol. If you have diabetes, this is the number the marketing should be quoting to you, and it generally is not.

Secondary endpoints

SURMOUNT-2 secondary endpoints, treatment against comparator. Last verified November 2026.
Endpoint	Treatment	Comparator	Difference
Lost at least 5% of body weight More than four in five got there despite diabetes being in the picture. This row and the others citing the trial's ClinicalTrials.gov results come from its on-treatment analysis, which runs a little higher than the treatment-regimen figures in the headline row. On that treatment-regimen basis, the paper reports 79% to 83% reaching this threshold against 32% on placebo.	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. Losses of that size 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, so the diabetes penalty is widest at the largest losses.	10 mg: 23.0%; 15 mg: 34.0%	1.0%	P<0.0001 for both doses
Three-month average blood sugar A larger blood-sugar reduction than the semaglutide counterpart trial reported (1.6 points), taking the average from 8.02% to about 5.8%. If your goal is diabetes control as much as weight, this is the result to weigh.	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%	Estimated treatment difference -24.2 percentage points (95% CI -28.6 to -19.6) for the 10 mg and 15 mg doses pooled; P<0.001
HDL, the other cholesterol Up about 8%, the direction usually treated as favorable.	+8.2%	+1.1%	—
LDL, the cholesterol that drives artery disease This one 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

SURMOUNT-2 adverse events, rate on treatment against rate on comparator. Last verified November 2026.
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. That is low given how many people reported stomach trouble: the side effects were unpleasant but tolerable for most.	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, partly because of a design choice rather than a property of the drug: nobody on insulin was allowed in, though sulfonylureas were permitted. If you take insulin, 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 made up 51% here against about two thirds of the non-diabetic trial, so the sexes were close to evenly balanced in this one.
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 across North and South America, Asia and Europe, making this among the most ethnically varied phase 3 trials in this drug class, which is an uncommon 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. What it does not resolve is 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 734 sellers on this register, 453 publish a standing monthly cash price for compounded tirzepatide, from $69 a month, with a median of $228.28.

⛔ 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

On its primary endpoint — How much body weight came off over 72 weeks, at each dose — the treatment arm recorded 10 mg: -12.8% (SE 0.6); 15 mg: -14.7% (SE 0.5) against -3.2% (SE 0.5) for the comparator. 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, with the same drug, the same top dose and a near-identical protocol. If you have diabetes, this is the number the marketing should be quoting to you, and it generally is not.

938 participants, over 72 weeks on treatment, the first 20 spent raising the dose, then 4 weeks of safety follow-up. It was a Phase 3 trial, finished; headline results published 2023. Registered as NCT04657003, which you can look up yourself rather than taking anyone's summary for it.

Adults aged 18 or older, BMI at least 27, 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. ⚠ A trial result describes the population it was measured in. If you differ from it materially — in age, in baseline weight, in whether you have diabetes — the number is context rather than a prediction.

The most commonly reported were stomach and bowel problems (10 mg and 15 mg pooled: most-common AE class; nausea, diarrhea, and vomiting predominated against Substantially lower on placebo on comparator), stopped the drug over a side effect (Under 5% across both tirzepatide arms against Similar low rate on placebo on comparator), serious adverse events of any kind (10 mg: 5.8% (18/312); 15 mg: 8.7% (27/311) against 7.3% (23/315) on comparator). Nausea, diarrhea and vomiting led, they were mostly mild to moderate, and they clustered into the 20 weeks while the dose was climbing. Rates come from this trial's population under its own dose-escalation schedule; a faster or slower titration changes what people experience.

Secondary endpoints included lost at least 5% of body weight (10 mg: 81.6%; 15 mg: 86.4% against 30.6%); lost at least a tenth of body weight (10 mg: 63.4%; 15 mg: 69.6% against 8.7%); lost at least 15% (10 mg: 41.4%; 15 mg: 51.8% against 2.6%). ⚠ Secondary endpoints are weaker evidence than the primary one — a trial is powered for its primary outcome, and the rest are read as supporting rather than as findings in their own right.

No, and this matters because the number gets used that way. SURMOUNT-2 tested Tirzepatide — the FDA-approved product, made by its manufacturer under Good Manufacturing Practice, at the doses and schedule the protocol specified. A compounded preparation of tirzepatide is a different product: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. ⛔ A seller quoting this trial's result beside a compounded price is quoting evidence that was generated on something they are not selling. That is not the same as saying compounded tirzepatide does not work — it is saying nobody measured it here.

It cannot tell you that. A trial reports an average across a defined population under a fixed protocol, with monitoring and adherence support most people do not get. It is the best evidence available and it is still a distribution rather than a promise — some participants lost far more than the mean and some lost nothing. What it is genuinely good for is comparing options against each other, which is what the rest of this section is for.

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.
7.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. PMID: 33567185.
8.Eli Lilly and Company. MOUNJARO (tirzepatide) injection: Prescribing Information. DailyMed (NIH/NLM). 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0
9.Eli Lilly and Company. ZEPBOUND (tirzepatide) injection: Prescribing Information. DailyMed (NIH/NLM). 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b