Primary outcome
What SURPASS-3 measured first
| 10 mg Tirzepatiden=291 | 15 mg Tirzepatiden=294 | Insulin Degludecn=317 |
|---|---|---|
| -2.20(0.051) | -2.37(0.050) | -1.34(0.049) |
Phase 3 · Tirzepatide
SURPASS-3 trial results
A Randomized, Phase 3, Open-Label Trial Comparing the Effect of LY3298176 Versus Titrated Insulin Degludec on Glycemic Control in Patients With Type 2 Diabetes
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) (Percentage of HbA1c), Baseline, Week 52. 10 mg Tirzepatide: -2.20; 15 mg Tirzepatide: -2.37; Insulin Degludec: -1.34.
- Participants
- 1,444
- Status
- completed
- Completed
- 2021-01-04
- Sponsor
- Eli Lilly and Company
As posted on ClinicalTrials.gov (NCT03882970), updated at source Jan 19, 2022. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Side effects by arm
Side effects in SURPASS-3
Percent of participants affected, Baseline Up To 56 Weeks. The most common events the registry lists.
| Event | 5 mg Tirzepatide | 10 mg Tirzepatide | 15 mg Tirzepatide | Insulin Degludec |
|---|---|---|---|---|
| Any serious event | 8.1% | 5.6% | 7.2% | 6.1% |
| Nausea | 11.5% | 22.5% | 23.7% | 1.7% |
| Diarrhoea | 15.4% | 16.4% | 15.6% | 3.9% |
| Decreased appetite | 6.1% | 10.3% | 12% | 0.6% |
| Vomiting | 5.9% | 9.4% | 10% | 1.1% |
| Dyspepsia | 3.9% | 8.9% | 5% | 0% |
| Abdominal pain | 2% | 4.7% | 6.4% | 1.1% |
| Nasopharyngitis | 3.1% | 3.9% | 4.2% | 6.1% |
| Lipase increased | 5.9% | 4.4% | 5.6% | 1.9% |
| Hypertension | 3.1% | 1.9% | 3.1% | 5.8% |
Secondary outcomes
What else it measured
| 5 mg Tirzepatiden=312 | Insulin Degludecn=317 |
|---|---|
| -1.93(0.050) | -1.34(0.049) |
| 5 mg Tirzepatiden=310 | 10 mg Tirzepatiden=291 | 15 mg Tirzepatiden=295 | Insulin Degludecn=317 |
|---|---|---|---|
| -7.5(0.37) | -10.7(0.37) | -12.9(0.37) | 2.3(0.37) |
| 5 mg Tirzepatiden=309 | 10 mg Tirzepatiden=291 | 15 mg Tirzepatiden=293 | Insulin Degludecn=314 |
|---|---|---|---|
| -48.2(1.82) | -54.8(1.86) | -59.2(1.85) | -55.7(1.81) |
| 5 mg Tirzepatiden=353 | 10 mg Tirzepatiden=350 | 15 mg Tirzepatiden=353 | Insulin Degludecn=351 |
|---|---|---|---|
| 82.44 | 89.71 | 92.63 | 61.25 |
| 5 mg Tirzepatiden=281 | 10 mg Tirzepatiden=263 | 15 mg Tirzepatiden=274 | Insulin Degludecn=288 |
|---|---|---|---|
| -52.6(1.20) | -59.7(1.22) | -60.6(1.20) | -48.0(1.18) |
| 5 mg Tirzepatiden=353 | 10 mg Tirzepatiden=350 | 15 mg Tirzepatiden=353 | Insulin Degludecn=351 |
|---|---|---|---|
| 66.01 | 83.71 | 87.82 | 6.27 |
| Measure | 5 mg Tirzepatiden=306 | 10 mg Tirzepatiden=293 | 15 mg Tirzepatiden=292 | Insulin Degludecn=313 |
|---|---|---|---|---|
| Hyperglycemia | -1.4(0.11) | -1.4(0.11) | -1.6(0.11) | -1.1(0.11) |
| Hypoglycemia | -1.1(0.12) | -0.9(0.12) | -1.0(0.12) | -0.7(0.12) |
| Treatment Satisfaction Score | 15.6(0.27) | 15.5(0.28) | 15.6(0.28) | 12.6(0.27) |
| 5 mg Tirzepatiden=356 | 10 mg Tirzepatiden=360 | 15 mg Tirzepatiden=359 | Insulin Degludecn=358 |
|---|---|---|---|
| 0.0137(0.0056) | 0.0108(0.0044) | 0.0275(0.0143) | 0.1020(0.0568) |
The trial
How SURPASS-3 was run
The purpose of this study is to compare the effect of the study drug tirzepatide to insulin degludec on blood sugar levels in participants with type 2 diabetes. The study will last about 67 weeks and may include up to 22 visits.
- 5 mg Tirzepatide: 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
- 10 mg Tirzepatide: 10 mg tirzepatide administered SC once a week.
- 15 mg Tirzepatide: 15 mg tirzepatide administered SC once a week.
- Insulin Degludec: Insulin degludec administered SC once a day.
Who could join the trial
Inclusion Criteria: * Participants must: * Have been diagnosed with type 2 diabetes mellitus (T2DM) * Have HbA1c between ≥7.0% and ≤10.5% * Be on stable treatment with unchanged dose of metformin or metformin plus an SGLT-2 inhibitor for at least 3 months before screening * Be of stable weight (± 5%) for at least 3 months before screening * Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening Exclusion Criteria: * Participants must not: * Have type 1 diabetes mellitus * Have had chronic or acute pancreatitis any time prior to study entry * Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment * Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss * Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if their ALT level is ≤3.0 the ULN for the reference range * Have an estimated glomerular filtration rate \<45 mL/minute/1.73 m2 (or lower than the country specific threshold for using the protocol required dose of metformin per local label) * Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months * Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2 * Have been taking any other diabetes medicines other than metformin, or metformin plus an SGLT-2 inhibitor during the last 3 months * Have been taking weight loss drugs, including over-the-counter medications during the last 3 months
Published papers
Papers from SURPASS-3
- Cusi K, Gastaldelli A, Lando LF, Sharma P, Torcello-Gomez A, Rodriguez A. Liver Fat Changes in Patients With Type 2 Diabetes by Presence of Genetic Hepatic Steatosis: A Post Hoc Analysis of SURPASS-3 MRI. Liver Int. 2026 Sep;46(9):e70837. doi: 10.1111/liv.70837.
- Sattar N, Neeland IJ, Dahlqvist Leinhard O, Fernandez Lando L, Bray R, Linge J, Rodriguez A. Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jun;13(6):482-493. doi: 10.1016/S2213-8587(25)00027-0. Epub 2025 Apr 30.
- De Block C, Peleshok J, Wilding JPH, Kwan AYM, Rasouli N, Maldonado JM, Wysham C, Liu M, Aleppo G, Benneyworth BD. Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics. Diabetes Ther. 2025 Jan;16(1):43-71. doi: 10.1007/s13300-024-01660-0. Epub 2024 Nov 12.
- Cariou B, Linge J, Neeland IJ, Dahlqvist Leinhard O, Petersson M, Fernandez Lando L, Bray R, Rodriguez A. Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes. Diabetes Obes Metab. 2024 Jun;26(6):2446-2455. doi: 10.1111/dom.15566. Epub 2024 Mar 26.
- Boye KS, Sapin H, Dong W, Williamson S, Lee CJ, Thieu VT. Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide. Diabetes Ther. 2023 Nov;14(11):1867-1887. doi: 10.1007/s13300-023-01457-7. Epub 2023 Sep 5.
- Boye KS, Thieu VT, Sapin H, Lee CJ, Lando LF, Brown K, Bray R, Wiese RJ, Patel H, Rodriguez A, Yu M. Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme. Diabetes Ther. 2023 Nov;14(11):1833-1852. doi: 10.1007/s13300-023-01451-z. Epub 2023 Aug 1.
- Viljoen A, Pantalone KM, Galindo RJ, Cui X, Huh R, Hemmingway A, Fernandez Lando L, Patel H. Time to Reach Glycaemic and Body Weight Loss Thresholds with Tirzepatide in Patients with Type 2 Diabetes: A Pre-planned Exploratory Analysis of SURPASS-2 and SURPASS-3. Diabetes Ther. 2023 May;14(5):925-936. doi: 10.1007/s13300-023-01398-1. Epub 2023 Mar 31.
- Gastaldelli A, Cusi K, Fernandez Lando L, Bray R, Brouwers B, Rodriguez A. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406. doi: 10.1016/S2213-8587(22)00070-5. Epub 2022 Apr 22.
- Battelino T, Bergenstal RM, Rodriguez A, Fernandez Lando L, Bray R, Tong Z, Brown K. Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):407-417. doi: 10.1016/S2213-8587(22)00077-8. Epub 2022 Apr 22.
- Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.
- Ludvik B, Giorgino F, Jodar E, Frias JP, Fernandez Lando L, Brown K, Bray R, Rodriguez A. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021 Aug 14;398(10300):583-598. doi: 10.1016/S0140-6736(21)01443-4. Epub 2021 Aug 6.
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
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