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Retatrutide-Diabetes
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
What are the results of monotherapy retatrutide in patients with type 2 diabetes from TRANSCEND-T2D-1?
In TRANSCEND‑T2D‑1, HbA1c mean change was −1.69%, −1.86%, and −1.94% with retatrutide 4, 9, and 12 mg vs −0.81% with placebo. Weight reduced by −11.5% (4mg) to −15.3% (12 mg), without a plateau at 40 weeks. Most common AEs were mild to moderate GI AEs.
Content Overview
What Is the Retatrutide TRANSCEND-T2D-1 Study Design?
Retatrutide is a novel, synthetic, investigational molecule, which is an agonist of the
- glucose-dependent insulinotropic polypeptide receptor (GIPR)
- glucagon-like peptide-1 receptor (GLP-1R), and
- glucagon receptor (GCGR).1
TRANSCEND-T2D-1 is a phase 3, 40-week, randomized multicenter, double-blind study to investigate the efficacy and safety of retatrutide once weekly compared with placebo in adults with type 2 diabetes (T2D) and inadequate glycemic control with diet and exercise alone (see TRANSCEND-T2D-1 Phase 3 Clinical Trial Design).2,3
The study included 537 adult participants from 48 sites across India, Mexico, and the United States. Participants were randomized 1:1:1:1 to receive either
- retatrutide 4 mg (n=134)
- retatrutide 9 mg (n=133)
- retatrutide 12 mg (n=136), or
- placebo (n=134).3
Dose was self-administered as a once-weekly subcutaneous injection with a multidose prefilled pen (KwikPen).3
The study is part of the retatrutide phase 3 development program in people with T2D.2
The primary efficacy endpoint is the change in HbA1c from baseline to week 40. Other key secondary endpoints were controlled for type I error.3
Figure 1 description: TRANSCEND-T2D-1 is a phase 3, randomized, multicenter, double-blind study to investigate the efficacy and safety of retatrutide once weekly compared with placebo once weekly. Participants were randomized 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg, or placebo dosed once weekly. Dosing of retatrutide 2 mg was started after up to a 4-week screening period. Doses (or sham) were escalated every 4 weeks until assigned maintenance dose. Primary endpoint was at 40 weeks, followed by a 4-week safety follow-up period.
Abbreviations: PBO = placebo; QW = every week.
TRANSCEND-T2D-1 Trial Inclusion and Exclusion Criteria
Inclusion and Exclusion Criteria for the TRANSCEND-T2D-1 Retatrutide Trial provides the inclusion and exclusion criteria for the TRANSCEND-T2D-1.
Inclusion Criteria | Exclusion Criteria |
|
|
Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; MEN = multiple endocrine neoplasia; MTC = medullary thyroid carcinoma; NYHA IV = New York Heart Association Functional Classification IV; T1D = type 1 diabetes; T2D = type 2 diabetes
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What Are the Efficacy Outcomes From the Retatrutide TRANSCEND-T2D-1 Trial?
In TRANSCEND-T2D-1, retatrutide met the primary and key secondary endpoints described in Primary and Secondary Efficacy Endpoints for the TRANSCEND-T2D-1 Retatrutide Clinical Trial.3
Participants in the study had a mean baseline
- duration of diabetes of 2.5 years
- HbA1c of 7.9%
- body weight of 96.9 kg, and
- BMI of 35.8 kg/m2 (see TRANSCEND-T2D-1 Baseline Characteristics of Randomized Population for additional baseline characteristics).3
Two statistical estimands, efficacy or treatment-regimen, were prespecified and used to evaluate efficacy of retatrutide from TRANSCEND-T2D-1:
- Efficacy estimand represents all randomized participants remaining on study intervention for 40 weeks without initiating additional antihyperglycemic medications (>14 days of use).
- Treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of additional antihyperglycemic medications.3
Efficacy Endpointa | Estimand | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
Primary Efficacy Endpoint, Week 40b | |||||
HbA1c, % Change from baseline | Treatment Regimen | -1.69 (0.11)c | -1.86 (0.10)c | -1.94 (0.08)c | -0.81 (0.12) |
Efficacy | -1.69 (0.10)c | -2.01 (0.07)c | -1.93 (0.06)c | -0.78 (0.12) | |
HbA1c, mmol/mol - Change from baseline | Treatment Regimen | -18.5 (1.22)c | -20.3 (1.06)c | -21.2 (0.93)c | -8.9 (1.26) |
Efficacy | -18.5 (1.07)c | -22.0 (0.79)c | -21.0 (0.70)c | -8.5 (1.35) | |
Key Secondary Endpoints, Week 40b | |||||
HbA1c <7.0% d, n (%) | Treatment Regimen | 109 (82%)c | 110 (83%)c | 121 (89%)c | 71 (52%) |
Efficacy | 112 (84%)c | 118 (89%)c | 124 (90%)c | 72 (52%) | |
HbA1c ≤6.5% d, n (%) | Treatment Regimen | 98 (75%)c | 99 (76%)c | 113 (83%)c | 56 (40%) |
Efficacy | 101 (77%)c | 110 (83%)c | 117 (85%)c | 56 (40%) | |
HbA1c <5.7% d, n (%) | Treatment Regimen | 46 (35%)e | 54 (40%)c | 50 (37%)c | 19 (14%) |
Efficacy | 49 (37%)e | 62 (46%)c | 53 (39%)c | 19 (14%) | |
Fasting serum glucose, mg/dL - Change from baseline | Treatment Regimen | -30.1 (4.23)e | -31.9 (3.80)c | -30.8 (3.58)c | -1.0 (4.51) |
Efficacy | -32.4 (3.42)e | -32.7 (2.84)c | -32.9 (2.84)c | 7.4 (5.64) | |
Body weight, kg - Change from baseline | Treatment Regimen | -11.1 (0.67)c | -13.5 (0.81)c | -15.1 (0.79)c | -2.7 (0.45) |
Efficacy | -11.1 (0.55)c | -15.1 (0.62)c | -16.6 (0.56)c | -2.8 (0.48) | |
Body weight, % - Change from baseline | Treatment Regimen | -11.5 (0.68)c | -13.9 (0.81)c | -15.3 (0.75)c | -2.6 (0.47) |
Efficacy | -11.5 (0.58)c | -15.5 (0.62)c | -16.8 (0.55)c | -2.5 (0.49) | |
≥5% body weight reduction d, n (%) | Treatment Regimen | 107 (80%)c | 102 (75%)c | 117 (85%)c | 35 (26%) |
Efficacy | 110 (82%)c | 113 (84%)c | 124 (90%)c | 38 (29%) | |
≥10% body weight reductiond, n (%) | Treatment Regimen | 68 (52%)c | 84 (63%)c | 94 (70%)c | 8 (7%) |
Efficacy | 73 (55%)c | 96 (73%) c | 102 (75%) c | 10 (8%) | |
≥15% body weight reduction, n (%) | Treatment Regimen | 41 (31%)e | 64 (48%)c | 68 (51%)c | 3 (3%) |
Efficacy | 44 (33%)e | 73 (55%)c | 75 (55%)c | 3 (3%) | |
HbA1c ≤6.5% and ≥10% BW reductiond, n (%) | Treatment Regimen | 54 (41%)c | 74 (56%)c | 86 (64%)c | 4 (3%) |
Efficacy | 58 (44%)c | 87 (65%)c | 93 (68%)c | 4 (3%) | |
Non-HDL cholesterol - % change from baseline | Treatment Regimen | -15.6 (2.34)e | -17.0 (2.34)f | -15.5 (2.07)g | -3.8 (2.67) |
Efficacy | -15.6 (2.37)e | -19.8 (2.35)c | -16.5 (2.10)h | -4.8 (3.00) | |
Triglycerides - % change from baseline | Treatment Regimen | -26.7 (3.05)e | -34.1 (2.98)c | -27.0 (3.24)c | -3.4 (4.13) |
Efficacy | -28.1 (3.04)e | -39.6 (2.33)c | -29.8 (3.32)c | -3.4 (4.77) | |
Systolic blood pressure, mm Hg - Change from baseline | Treatment Regimen | -5.0 (0.92)e | -4.7 (0.82)i | -5.4 (0.80)j | -1.5 (0.69) |
Efficacy | -5.1 (0.89)e | -5.8 (0.65)c | -6.4 (0.67)c | -1.6 (0.69) | |
Abbreviations: BW = body weight; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein
aData are model-based estimate and standard error for changes at Week 40 from baseline.
bControlled for type I error.
cp<.0001 vs placebo.
dData are m (%) at 40 weeks. m was calculated by averaging the number of participants achieving the target across imputed datasets and then rounded to integer. Model-based estimate (%), risk difference, confidence interval, and p value are from logistic regression model using imputed data combined with the use of Rubin’s rule.
eData for retatrutide 4 mg are considered additional secondary endpoints.
fp = .0002 vs placebo.
gp = .0004 vs placebo.
hp = .0011 vs placebo.
ip = .0014 vs placebo.
jp = .0001 vs placebo.
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What are the Safety Outcomes from the Retatrutide TRANSCEND-T2D-1 Trial?
Adverse events (AEs) occurred in
- 63% in the retatrutide 4 mg group
- 64% in the retatrutide 9 mg group
- 63% in the retatrutide 12 mg group, and
- 57% in the placebo group.3
Gastrointestinal AEs were the most commonly reported events in retatrutide-treated participants. These events were mostly mild to moderate in severity, occurred primarily during the dose-escalation period, and subsided over time.3
See Safety Outcomes in the TRANSCEND-T2D-1 Retatrutide Clinical Trial for additional details.
Adverse Eventa, n (%) | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
Participants with ≥1 TEAE | 84 (63%) | 85 (64%) | 85 (63%) | 77 (57%) |
Serious AEs | 6 (4%) | 1 (1%) | 5 (4%) | 2 (1%) |
Deathsb | 2 (1%) | 0 | 0 | 0 |
AEs leading to study intervention discontinuation | 3 (2%) | 6 (5%) | 7 (5%) | 0 |
Gastrointestinal AEs leading to discontinuation | 0 | 1 (1%) | 4 (3%) | 0 |
Upper abdominal pain | 0 | 0 | 1 (1%) | 0 |
Constipation | 0 | 0 | 1 (1%) | 0 |
Dyspepsia | 0 | 0 | 1 (1%) | 0 |
Nausea | 0 | 1 (1%) | 1 (1%) | 0 |
TEAEs occurring in ≥5% of participants | ||||
Diarrhea | 25 (19%) | 35 (26%) | 31 (23%) | 6 (4%) |
Nausea | 22 (16%) | 26 (20%) | 36 (26%) | 5 (4%) |
Vomiting | 21 (16%) | 20 (15%) | 24 (18%) | 3 (2%) |
Hyperglycemia | 5 (4%) | 10 (8%) | 5 (4%) | 35 (26%) |
Decreased appetite | 10 (7%) | 15 (11%) | 11 (8%) | 2 (1%) |
Headache | 5 (4%) | 8 (6%) | 7 (5%) | 13 (10%) |
Abdominal distension | 7 (5%) | 8 (6%) | 13 (10%) | 3 (2%) |
Constipation | 6 (4%) | 11 (8%) | 10 (7%) | 1 (1%) |
Asthenia | 5 (4%) | 5 (4%) | 5 (4%) | 9 (7%) |
Fatigue | 1 (1%) | 8 (6%) | 10 (7%) | 4 (3%) |
Pain | 3 (2%) | 5 (4%) | 4 (3%) | 11 (8%) |
Abdominal discomfort | 6 (4%) | 10 (8%) | 4 (3%) | 1 (1%) |
Nasopharyngitis | 6 (4%) | 2 (2%) | 4 (3%) | 9 (7%) |
Upper abdominal pain | 7 (5%) | 1 (1%) | 5 (4%) | 7 (5%) |
Back pain | 4 (3%) | 3 (2%) | 2 (1%) | 10 (7%) |
Eructation | 1 (1%) | 2 (2%) | 7 (5%) | 0 |
Other TEAEs of Interest | ||||
Hypoglycemia (blood glucose <54 mg/dL) | 0 | 2 (2%) | 1 (1%) | 0 |
Severe Hypoglycemia | 0 | 0 | 0 | 0 |
Initiation of rescue therapy for severe hyperglycemia | 3 (2%) | 9 (7%) | 2 (1%) | 26 (19%) |
Arrhythmias and cardiac conduction disorders | 4 (3%) | 2 (2%) | 1 (1%) | 0 |
Malignancies | 3 (2%) | 0 | 0 | 1 (1%) |
Adjudication-confirmed major adverse cardiovascular events | 3 (2%) | 0 | 0 | 0 |
Cholelithiasis | 0 | 1 (1%) | 3 (2%) | 0 |
Dysesthesia | 6 (4%) | 3 (2%) | 6 (4%) | 0 |
Injection site reactions | 2 (1%) | 2 (2%) | 2 (1%) | 1 (1%) |
Abbreviations: AE = adverse event; TEAE = treatment-emergent adverse event.
aParticipants may be counted in more than one category. Number of episodes were reported if available.
bDeaths also included as serious AEs and discontinuation due to AE.
In the trial, there were no cases of
- pancreatitis
- drug-induced liver injury
- severe hypoglycemia, or
- medullary thyroid cancer.3
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Baseline Characteristics of TRANSCEND-T2D-1 Participants
Characteristica | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
Age, years | 47.9 ± 12.2 | 50.2 ± 12.1 | 49.2 ± 12.1 | 48.0 ± 12.2 |
Female, n (%) | 71 (53%) | 79 (59%) | 80 (59%) | 66 (49%) |
Race, n (%) | ||||
American Indian or Alaska Native | 50 (37%) | 50 (38%) | 49 (36%) | 45 (34%) |
Asian | 41 (31%) | 41 (31%) | 43 (32%) | 45 (34%) |
Black or African American | 5 (4%) | 5 (4%) | 8 (6%) | 9 (7%) |
White | 36 (27%) | 33 (25%) | 35 (26%) | 35 (26%) |
Ethnicity, n (%) | ||||
Hispanic or Latino | 72 (54%) | 71 (53%) | 71 (52%) | 69 (51%) |
Not Hispanic or Latino | 62 (46%) | 62 (47%) | 65 (48%) | 65 (49%) |
Country, n (%) | ||||
India | 41 (31%) | 40 (30%) | 41 (30%) | 42 (31%) |
Mexico | 54 (40%) | 54 (41%) | 55 (40%) | 53 (40%) |
United States | 39 (29%) | 39 (29%) | 40 (29%) | 39 (29%) |
HbA1c concentration | ||||
% | 7.9 ± 1.1 | 8.0 ± 1.0 | 7.9 ± 1.0 | 7.9 ± 1.1 |
mmol/mol | 63.1 ± 11.9 | 64.4 ± 11.3 | 62.7 ± 10.8 | 62.5 ± 12.1 |
HbA1c category | ||||
≤8·0%, n (%) | 79 (59%) | 70 (53%) | 90 (66%) | 85 (63%) |
>8·0%, n (%) | 55 (41%) | 63 (47%) | 46 (34%) | 49 (37%) |
Fasting serum glucose concentration | ||||
mg/dL | 137.8 ± 52.6 | 144.7 ± 59.6 | 129.9 ± 53.3 | 131.8 ± 51.8 |
mmol/L | 7.7 ± 2.9 | 8.0 ± 3.3 | 7.2 ± 3.0 | 7.3 ± 2.9 |
Duration of T2D, years | 2.3 ± 4.3 | 2.9 ± 5.3 | 2.5 ± 4.0 | 2.4 ± 4.1 |
Prior use of antihyperglycemic medications, n (%) | 23 (17%) | 20 (15%) | 20 (15%) | 19 (14%) |
Body weight, kg | 99.6 ± 23.3 | 95.1 ± 21.9 | 99.6 ± 25.1 | 93.3 ± 18.6 |
BMI, kg/m² | 36.6 ± 7.4 | 35.6 ± 6.7 | 36.4 ± 7.1 | 34.7 ± 6.5 |
Waist circumference, cm | 113.7 ± 15.9 | 110.4 ± 13.9 | 113.3 ± 16.6 | 109.2 ± 13.9 |
Triglycerides, mg/dL | 176.9 ± 138.3 | 174.2 ± 124.8 | 172.7 ± 102.9 | 174.7 ± 105.6 |
Non-HDL cholesterol, mg/dL | 135.3 ± 39.0 | 138.4 ± 39.0 | 139.4 ± 38.8 | 142.9 ± 40.4 |
Blood pressure, mmHg | ||||
Systolic | 124.4 ± 10.0 | 125.7 ± 11.0 | 125.4 ± 10.9 | 124.2 ± 9.9 |
Diastolic | 79.6 ± 7.0 | 79.2 ± 7.8 | 79.3 ± 6.2 | 79.0 ± 6.8 |
eGFR, mL/min/1.73 m² | 85.0 ± 22.5 | 88.3 ± 22.4 | 86.7 ± 22.1 | 87.0 ± 23.2 |
Abbreviations: BMI = body mass index; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; T2D = type 2 diabetes.
aData are mean ± SD, unless otherwise indicated.
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Future Retatrutide Program Results
Retatrutide is an investigational molecule currently in phase 3 clinical trials, several of which are expected to complete in 2026. Depending on trial completion and regulatory process, type 2 diabetes submission is anticipated for 2027.4
Date of Last Review: 18-May-2026
References
1Jastreboff AM, Kaplan LM, Frías JP, et al; Retatrutide Phase 2 Obesity Trial Investigators. Triple–hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389(6):514-526. https://doi.org/10.1056/nejmoa2301972
2Effect of retatrutide compared with placebo in adult participants with type 2 diabetes and inadequate glycemic control with diet and exercise alone (TRANSCEND-T2D-1). ClinicalTrials.gov identifier: NCT06354660. Updated April 27, 2025. Accessed April 27, 2025. https://clinicaltrials.gov/study/NCT06354660
3Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet. Epub ahead of print June 6, 2026. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00967-0
4Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: May 18, 2026