Scientific deep-dive

Retatrutide for type 2 diabetes: Phase 2 evidence and what TRIUMPH-2 is testing

Retatrutide is investigational only as of May 2026 — not FDA-approved for T2D anywhere. The Phase 2 T2D trial (Rosenstock 2023, n=281) produced HbA1c reductions up to -2.02% at 12 mg vs -1.41% dulaglutide. TRIUMPH-2 Phase 3 is Active-Not-Recruiting, est. completion May 2026.

By Eli Marsden · Founding Editor
Editorially reviewed (not clinically reviewed) · How we verify contentLast reviewed
18 min read·10 citations

This YMYL evidence review is part of Weight Loss Rankings’ living editorial database — 300+ research articles and 190+ clinically-reviewed GLP-1 telehealth providers, sourced only from FDA prescribing information on DailyMed and peer-reviewed PubMed literature.

Retatrutide is an Eli Lilly investigational triple agonist at the GIP, GLP-1, and glucagon receptors. It is NOT FDA-approved — for type 2 diabetes or any other indication — anywhere worldwide as of May 2026. The dedicated Phase 3 T2D registrational trial TRIUMPH-2 (ClinicalTrials.gov NCT05929079) is Active-Not-Recruiting with an estimated completion date of May 2026; no Phase 3 T2D readout has yet been published. The currently FDA-approved triple-class-style precedent for T2D is tirzepatide (Mounjaro, approved May 13, 2022), a dual GIP/GLP-1 receptor agonist. This article walks through what the Phase 2 T2D trial (Rosenstock 2023, PMID 37385280) actually showed, the body composition substudy (Coskun 2025), the appetite substudy (Kanu 2025), the mechanistic rationale (Coskun 2022, Li 2024), and the SURPASS and SUSTAIN reference points needed to interpret cross-trial comparisons.

The honest answer

Retatrutide is investigational only. NOT FDA-approved for T2D (or any indication) anywhere worldwide as of May 2026. TRIUMPH-2 Phase 3 T2D readout expected late 2026 per ClinicalTrials.gov NCT05929079. The FDA-approved triple-class precedent today is tirzepatide (Mounjaro, May 13 2022). The Phase 2 Rosenstock 2023 trial is the entire published T2D evidence base.

At a glance

  • Not FDA-approved. Retatrutide (LY3437943) is investigational only as of May 2026 — not approved for T2D, for obesity, for sleep apnea, or for any indication worldwide.
  • Triple agonist mechanism. Simultaneous engagement of GIP, GLP-1, and glucagon receptors with GIP-favored activity ratio (R-GIPR > R-GLP-1R > R-GCGR) designed to balance glucagon-driven energy expenditure against hyperglycemia risk[2].
  • Rosenstock 2023 (PMID 37385280) — Phase 2 T2D trial in 281 adults. HbA1c at 24 weeks: -0.43% / -1.39% / -1.30% / -1.99% / -1.88% / -2.02% across ascending retatrutide arms versus -0.01% placebo and -1.41% dulaglutide 1.5 mg[1].
  • 36-week weight reductions in Rosenstock 2023 reached -16.94% at retatrutide 12 mg, vs -3.00% placebo and -2.02% dulaglutide[1].
  • Body composition substudy (Coskun 2025, PMID 40609566): fat mass loss dose-dependent up to 26.1% at the 8 mg pooled arm; lean-to-total-weight-loss ratio similar to other obesity drugs[5].
  • NO severe hypoglycemia, no deaths across all 281 Phase 2 participants — consistent with glucose-dependent incretin secretion when used without insulin or sulfonylurea[1].
  • TRIUMPH-2 Phase 3 T2D trial (NCT05929079) is Active-Not-Recruiting with estimated completion May 2026; no Phase 3 T2D readout published as of the verification date[7].

What type 2 diabetes is, and why triple-class matters

Type 2 diabetes (T2D) is a chronic metabolic condition characterized by insulin resistance and progressive beta-cell dysfunction. Hallmark clinical features include elevated fasting glucose, elevated HbA1c (typically ≥ 6.5% on the FDA-cleared diagnostic threshold), and progressive risk of cardiovascular, renal, retinal, and neuropathic complications when glycemic control is not maintained. The therapeutic goal in pharmacologic T2D management is to reduce HbA1c to an individualized target (typically < 7.0% for most non-pregnant adults, per ADA guidance) while minimizing hypoglycemia risk and addressing weight, cardiovascular, and renal comorbidities.

The modern T2D pharmacologic landscape uses several mechanistic classes: biguanides (metformin), SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, basal and prandial insulins, selective GLP-1 receptor agonists (semaglutide, dulaglutide, liraglutide), and — since the Mounjaro approval on May 13, 2022 — the dual GIP/GLP-1 receptor agonist tirzepatide. Each class engages different physiological levers for glucose control and weight effect.

The triple GIP/GLP-1/glucagon mechanism is conceptually distinct because it adds a glucagon-receptor-agonist arm on top of the incretin mechanisms. The biological rationale: glucagon receptor agonism increases hepatic glucose output and resting energy expenditure (calorie burn), but in isolation would worsen glycemic control. When combined with potent GIP and GLP-1 agonism — which together drive insulin secretion in a glucose-dependent manner, suppress glucagon secretion in the hyperglycemic state, and delay gastric emptying — the net effect on HbA1c can remain favorable while capturing the energy-expenditure benefit. The Coskun 2022 Cell Metab paper details the GIP-favored receptor activity ratio designed to achieve this balance[2].

Whether the triple-class mechanism translates into clinically meaningfully larger A1c or weight reductions in T2D than tirzepatide already produces is the question TRIUMPH-2 is designed to answer. For the broader mechanism review across indications, see retatrutide triple-agonist evidence review.

Mechanism primer: how retatrutide works

Retatrutide (Eli Lilly compound LY3437943) is a single-molecule peptide agonist that simultaneously engages three incretin-superfamily receptors: the GIP receptor (GIPR), the GLP-1 receptor (GLP-1R), and the glucagon receptor (GCGR). The compound’s discovery and proof-of-concept characterization were published in Coskun 2022 Cell Metab (PMID 35985340), which describes the molecular design choices intended to balance the three signaling pathways[2].

Key design features:

  • Receptor activity ratio. Coskun 2022 reports the intrinsic activity profile as R-GIPR > R-GLP-1R > R-GCGR. GIP-favored activity is intended to maximize the incretin glucose-dependent insulin secretion effect; moderate GLP-1R activity contributes additional insulinotropic, anorectic, and gastric-emptying effects; lower-magnitude GCGR activity is intended to engage hepatic glucose handling and resting energy expenditure without overwhelming the incretin-driven glycemic control.
  • Once-weekly subcutaneous administration. The peptide was engineered for a half-life consistent with once-weekly dosing — matching the prevailing dosing cadence for tirzepatide, semaglutide, and dulaglutide.
  • Delayed gastric emptying. Urva 2023 Diabetes Obes Metab (PMID 37311727) demonstrated measurable retatrutide-induced delay of gastric emptying, consistent with the GLP-1R agonist class and contributing both to the postprandial glucose effect and to the dose-dependent gastrointestinal side-effect profile observed in clinical trials[4].
  • Structural basis. Li 2024 Cell Discov (PMID 39019866) published cryo-electron microscopy structures of retatrutide engaged with each of the three receptors, providing the structural framework for understanding the simultaneous receptor engagement[3].

The clinical Phase 2 program tested whether this molecular profile translates into clinically meaningful T2D efficacy and acceptable safety. Rosenstock 2023 is the Phase 2 T2D readout.

The Phase 2 T2D pivotal: Rosenstock 2023 in detail

Rosenstock 2023 Lancet (PMID 37385280) is the load-bearing published evidence for retatrutide in type 2 diabetes as of 2026-05-25[1]. Design and population:

  • Trial design. Randomized, double-blind, placebo- and active-controlled, parallel-group, Phase 2, multicenter trial conducted in the USA. ClinicalTrials.gov NCT04867785.
  • Population. Adults with type 2 diabetes inadequately controlled on diet and exercise alone OR on metformin monotherapy. n=281 randomized across 8 arms.
  • Eight arms. Placebo (n=45); dulaglutide 1.5 mg weekly active comparator (n=46); retatrutide 0.5 mg weekly (n=47); retatrutide 4 mg with escalation schedule (n=23); retatrutide 4 mg with no escalation (n=24); retatrutide 8 mg with slow escalation (n=26); retatrutide 8 mg with fast escalation (n=24); retatrutide 12 mg with escalation (n=46). 275 patients were included in efficacy analyses. 237 patients (84%) completed the trial.
  • Primary endpoint. Change in HbA1c from baseline to 24 weeks.
  • Treatment duration. 36-week intervention period with the primary endpoint at 24 weeks.

Headline glycemic results at the 24-week primary endpoint (LS-mean change in HbA1c from baseline):

  • Placebo: -0.01 percentage points (essentially no change).
  • Dulaglutide 1.5 mg: -1.41 percentage points.
  • Retatrutide 0.5 mg: -0.43 percentage points.
  • Retatrutide 4 mg (escalation): -1.39 percentage points.
  • Retatrutide 4 mg (no escalation): -1.30 percentage points.
  • Retatrutide 8 mg (slow escalation): -1.99 percentage points.
  • Retatrutide 8 mg (fast escalation): -1.88 percentage points.
  • Retatrutide 12 mg (escalation): -2.02 percentage points.

Statistical comparisons versus the dulaglutide 1.5 mg active comparator were reported. Retatrutide 8 mg slow escalation produced statistically significantly greater HbA1c reduction than dulaglutide (p=0.0019), and retatrutide 12 mg also produced statistically significantly greater HbA1c reduction (p=0.0002). The lower retatrutide doses (0.5 mg and 4 mg arms) were not statistically superior to dulaglutide[1].

Body-weight reductions at 36 weeks were dose-dependent:

  • Placebo: -3.00%.
  • Dulaglutide 1.5 mg: -2.02%.
  • Retatrutide 0.5 mg: -3.19%.
  • Retatrutide 4 mg escalation: -7.92%.
  • Retatrutide 4 mg no escalation: -10.37%.
  • Retatrutide 8 mg slow escalation: -16.81%.
  • Retatrutide 8 mg fast escalation: -16.34%.
  • Retatrutide 12 mg escalation: -16.94%.

All retatrutide arms at ≥ 4 mg produced statistically significantly greater body-weight reduction than dulaglutide 1.5 mg (P<0.0001). The magnitude of body-weight reduction at the 8 mg and 12 mg doses (approximately 16-17%) is larger than what tirzepatide 15 mg produced in SURPASS-2 on a metformin background — though direct cross-trial comparison is not statistically valid (different populations, different durations, different active comparators)[8].

Safety highlights from Rosenstock 2023:

  • No severe hypoglycemia across any of the 281 participants. No deaths.
  • Mild-to-moderate gastrointestinal adverse events (nausea, diarrhea, vomiting, constipation) were reported in approximately 35% of retatrutide-treated patients pooled, ranging from 13% at the 0.5 mg dose to 50% at the 8 mg fast-escalation dose. Placebo GI AE rate was 13% and dulaglutide GI AE rate was 35%.
  • GI events were dose-dependent and escalation-schedule-dependent. At a matched final dose, slow escalation produced a lower GI burden than fast escalation — the same pattern observed with tirzepatide and semaglutide.

Magnitude comparison

Rosenstock 2023 Phase 2 T2D — LS-mean HbA1c reduction at 24 weeks across placebo, dulaglutide 1.5 mg active comparator, and retatrutide ascending-dose arms. Retatrutide 8 mg slow escalation and 12 mg escalation produced statistically significantly greater HbA1c reduction than dulaglutide 1.5 mg. No severe hypoglycemia or deaths were reported.[1]

  • Placebo0.01 % points
    essentially no change
  • Dulaglutide 1.5 mg (active comparator)1.41 % points
  • Retatrutide 0.5 mg0.43 % points
  • Retatrutide 4 mg (escalation)1.39 % points
  • Retatrutide 8 mg (slow escalation)1.99 % points
    p=0.0019 vs dulaglutide
  • Retatrutide 12 mg (escalation)2.02 % points
    p=0.0002 vs dulaglutide
Rosenstock 2023 Phase 2 T2D — LS-mean HbA1c reduction at 24 weeks across placebo, dulaglutide 1.5 mg active comparator, and retatrutide ascending-dose arms. Retatrutide 8 mg slow escalation and 12 mg escalation produced statistically significantly greater HbA1c reduction than dulaglutide 1.5 mg. No severe hypoglycemia or deaths were reported.

Body composition substudy: Coskun 2025

The Coskun 2025 Lancet Diabetes Endocrinol body-composition substudy (PMID 40609566) reports DXA-measured fat mass and lean mass changes in a subset of the Rosenstock 2023 trial participants[5]. Substudy participation:

  • n=189 enrolled into the body composition substudy across the eight Rosenstock 2023 arms.
  • n=155 with baseline DXA scans.
  • n=103 with paired baseline + 36-week DXA scans (the analysis population for paired comparisons).

Fat mass percentage reduction at 36 weeks:

  • Placebo: 4.5%.
  • Dulaglutide 1.5 mg: 2.6%.
  • Retatrutide 0.5 mg: 4.9%.
  • Retatrutide 4 mg (pooled escalation + no-escalation arms): 15.2%.
  • Retatrutide 8 mg (pooled slow + fast escalation arms): 26.1%.
  • Retatrutide 12 mg: 23.2%.

LS-mean fat mass change versus placebo:

  • Retatrutide 0.5 mg: -0.4 kg (p=0.83, not significant).
  • Retatrutide 4 mg pooled: -10.7 kg (p=0.0013).
  • Retatrutide 8 mg pooled: -21.6 kg (p<0.0001).
  • Retatrutide 12 mg: -18.7 kg (p<0.0001).

The critical body composition finding: the proportion of lean mass loss relative to total weight loss was similar to what other obesity treatments produce. In other words, retatrutide did not produce a disproportionately greater lean-mass loss than what is observed with FDA-approved incretin-class agents at comparable weight-loss magnitudes. The lean-loss ratio interpretation provides reassurance that the large absolute weight reductions are driven primarily by fat mass reduction, not by excess lean tissue catabolism[5].

For the practical implications of GLP-1-class lean-mass loss and the role of resistance training, see related discussion in the broader retatrutide evidence review at retatrutide triple-agonist evidence.

Appetite and eating behavior: Kanu 2025

The Kanu 2025 Diabetes Obesity & Metabolism substudy (PMID 40916752) reports appetite Visual Analogue Scale (VAS) and Eating Inventory (EI) measurements during the Rosenstock 2023 Phase 2 trial[6]. Substudy design:

  • n=275 Phase 2 T2D adults assessed at weeks 24 and 36.
  • Appetite VAS. Validated visual analogue scale measurements of overall appetite, hunger, satiety, prospective food consumption, and desire to eat.
  • Eating Inventory (EI). Validated three-factor questionnaire measuring Dietary Restraint, Disinhibition, and Perceived Hunger.

Key findings:

  • Retatrutide ≥ 4 mg reduced overall appetite, hunger, and prospective food consumption versus placebo (p<0.05).
  • EI Perceived Hunger and Disinhibition improved at retatrutide 8 mg and 12 mg at both weeks 24 and 36.
  • EI Dietary Restraint increased versus placebo only at the 12 mg dose at week 36.
  • Behavioral correlations with weight loss: reductions in Perceived Hunger correlated with weight loss (r = 0.28); reductions in Disinhibition correlated with weight loss (r = 0.36); increases in Dietary Restraint correlated with weight loss (r = 0.31).

The behavioral pattern is consistent with the incretin-class appetite-suppression mechanism: reduced hunger and reduced disinhibited eating, paired with increased dietary restraint, all contributing to the energy-deficit substrate for weight loss. This mechanistic profile is similar to what has been characterized for semaglutide and tirzepatide in their respective Phase 3 obesity programs.

Head-to-head context: SURPASS-1, SURPASS-2, SUSTAIN-7

Cross-trial comparisons between Rosenstock 2023 retatrutide Phase 2 data and the FDA-approved comparators are not statistically valid (different durations, different populations, different active comparators). The reference points below are useful for orientation only.

SURPASS-1 (Rosenstock 2021): tirzepatide monotherapy benchmark

SURPASS-1 (PMID 34186022) was a 40-week, double-blind, placebo- controlled, Phase 3 trial in 478 drug-naive T2D adults randomized to tirzepatide 5/10/15 mg weekly vs placebo[9]. HbA1c reductions were -1.87% / -1.89% / -2.07% at the three tirzepatide doses versus +0.04% on placebo (all P<0.0001). Dose-dependent weight reduction ranged from 7.0 to 9.5 kg. SURPASS-1 is the FDA-approved dual GIP/GLP-1 monotherapy benchmark for T2D.

SURPASS-2 (Frías 2021): tirzepatide vs semaglutide head-to-head

SURPASS-2 (PMID 34170647) was a 40-week, open-label, Phase 3 trial in 1,879 T2D adults on metformin background, randomized to tirzepatide 5/10/15 mg weekly versus semaglutide 1 mg weekly[8]. HbA1c reductions were -2.01 / -2.24 / -2.30 percentage points (tirzepatide) versus -1.86 (semaglutide). Body-weight treatment differences versus semaglutide were -1.9 kg, -3.6 kg, and -5.5 kg respectively (all P<0.001). SURPASS-2 is the FDA-approved triple-class precedent for the question “does triple-mechanism beat dual-mechanism for T2D?” — with the answer that tirzepatide’s dual mechanism beats semaglutide’s selective GLP-1 mechanism on both endpoints.

SUSTAIN-7 (Pratley 2018): semaglutide vs dulaglutide

SUSTAIN-7 (PMID 29397376) was a 40-week, open-label, Phase 3b trial in 1,201 T2D adults randomized to semaglutide 0.5 mg or 1.0 mg weekly versus dulaglutide 0.75 mg or 1.5 mg weekly[10]. HbA1c reductions: sema 0.5 mg -1.5% vs dula 0.75 mg -1.1% (estimated treatment difference -0.40, P<0.0001); sema 1.0 mg -1.8% vs dula 1.5 mg -1.4% (ETD -0.41, P<0.0001). Weight: sema 1.0 mg -6.5 kg vs dula 1.5 mg -3.0 kg (P<0.0001). SUSTAIN-7 is the closest GLP-1-only comparator scaffold for understanding what dulaglutide 1.5 mg — the active comparator in Rosenstock 2023 — looks like across the broader GLP-1 class.

The implication: retatrutide 12 mg in Phase 2 (HbA1c -2.02% at 24 wk vs dulaglutide 1.5 mg -1.41%) and tirzepatide 15 mg in SURPASS-2 (HbA1c -2.30% at 40 wk vs semaglutide 1 mg -1.86%) are roughly comparable in magnitude, but the trial designs differ enough that the TRIUMPH-2 Phase 3 readout is required for any direct retatrutide vs tirzepatide claim in T2D. For more cross-trial analysis, see retatrutide vs tirzepatide head-to-head evidence and Mounjaro vs Ozempic SURPASS-2 evidence review.

What TRIUMPH-2 Phase 3 is testing

TRIUMPH-2 (ClinicalTrials.gov NCT05929079) is Eli Lilly’s dedicated Phase 3 registrational trial of retatrutide in adults with type 2 diabetes. The broader TRIUMPH program design across obesity, sleep apnea, knee osteoarthritis, and T2D is summarized in Giblin 2026 Diabetes Obes Metab (PMID 41090431)[7].

Status as of 2026-05-25 per ClinicalTrials.gov:

  • Status: Active, Not Recruiting.
  • Estimated completion: May 2026.
  • Phase 3 T2D readout status: No peer-reviewed publication of TRIUMPH-2 efficacy or safety endpoints has yet been released. Framing in this article reflects the published evidence base as of the verification date; the TRIUMPH-2 readout is anticipated to publish in the late 2026 timeframe per the ClinicalTrials.gov estimated completion date, though no FDA submission timeline has been confirmed publicly.

Once TRIUMPH-2 publishes, it — not Rosenstock 2023 Phase 2 — will become the load-bearing evidence base for retatrutide in T2D. Any decision to write or prescribe retatrutide for T2D would depend on subsequent FDA review and approval, which has not occurred as of the verification date. For the broader regulatory and access timeline, see retatrutide approval and access timeline.

Practical takeaway: what this means for T2D adults today

Retatrutide is investigational only. Practical implications:

  • Retatrutide cannot be prescribed for T2D today. It is not FDA-approved for any indication. Any source claiming to dispense “retatrutide” outside an authorized clinical trial is operating outside the FDA-regulated supply chain. See retatrutide buy / regulatory sourcing evidence for the regulatory framing.
  • The FDA-approved triple-class-style precedent for T2D is tirzepatide (Mounjaro). Mounjaro was approved May 13, 2022 (Drugs@FDA ApplNo 215866). SURPASS-1 through SURPASS-5 establish the Phase 3 evidence base.
  • For T2D adults already on metformin who need intensification — the conversation today is between continuing metformin, adding an SGLT2 inhibitor, adding a selective GLP-1 receptor agonist (semaglutide or dulaglutide), adding the dual GIP/GLP-1 agonist tirzepatide, or moving to basal insulin, all based on individualized cardiorenal, weight, and tolerance considerations. See tirzepatide-metformin combination evidence for the direct triple-class precedent on a metformin background.
  • If TRIUMPH-2 reads out favorably and retatrutide is later FDA-approved for T2D — the practical management considerations (titration schedule, GI side-effect timeline, insulin/sulfonylurea dose adjustment for hypoglycemia mitigation, renal-impairment use) will mirror the existing tirzepatide and semaglutide playbooks but with retatrutide-specific dosing and labeling. Until then, those decisions remain theoretical.
  • Defer to a licensed prescriber for any treatment decision. This article is educational content about the published Phase 2 evidence base, not a recommendation to use any specific therapy.

Frequently asked questions

References

  1. 1.Rosenstock J, Frias JP, Rodbard HW, Tofé S, Sears E, Huh R, Fernández Landó L, Patel H. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. n=281 across 8 arms (placebo, dulaglutide 1.5 mg, retatrutide 0.5 mg, 4 mg esc, 4 mg no-esc, 8 mg slow esc, 8 mg fast esc, 12 mg esc). Primary endpoint HbA1c at 24 weeks. LS-mean HbA1c change: -0.43% / -1.39% / -1.30% / -1.99% / -1.88% / -2.02% (retatrutide arms ascending dose) vs -0.01% placebo and -1.41% dulaglutide. 8 mg slow esc (p=0.0019) and 12 mg (p=0.0002) significantly greater than dulaglutide. Bodyweight at 36 wk: -3.19% to -16.94% across retatrutide doses vs -3.00% placebo and -2.02% dulaglutide. NO severe hypoglycemia. No deaths. Lancet. 2023. PMID: 37385280.
  2. 2.Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Original pharmacology paper describing the molecular design of retatrutide and the GIP-favored receptor activity ratio (R-GIPR > R-GLP-1R > R-GCGR) intended to balance glucagon-mediated energy expenditure against hyperglycemia risk. Cell Metab. 2022. PMID: 35985340.
  3. 3.Li W, Yang X, Xu C, Tan L, Wu S, Tang K, Zhao M, Zhang H, Du Y, Liu Q, Wu B, Lin S, Wang MW, Yang D, Cong Z, Shen Q. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cryo-EM structural paper describing simultaneous engagement of GLP-1R, GIPR, and GCGR by retatrutide and the structural basis for the triple-agonist pharmacology. Cell Discov. 2024. PMID: 39019866.
  4. 4.Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z. The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Mechanistic study confirming retatrutide produces measurable delayed gastric emptying — consistent with the general incretin class and relevant to the dose-dependent GI side-effect profile. Diabetes Obes Metab. 2023. PMID: 37311727.
  5. 5.Coskun T, Hernandez-Illas M, Stefanski A, Mao H, Gurbuz S, Du Y, Thomas MK, Haupt A, Robins DA, Hartman ML. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. DXA substudy of Rosenstock 2023. n=189 enrolled; n=155 baseline DXA; n=103 paired baseline + 36-week DXA. Fat mass % reduction: 4.9% / 15.2% / 26.1% / 23.2% (retatrutide 0.5, 4 mg pooled, 8 mg pooled, 12 mg) vs 2.6% dulaglutide and 4.5% placebo. Proportion of lean mass loss to total weight loss similar to other obesity treatments. Lancet Diabetes Endocrinol. 2025. PMID: 40609566.
  6. 6.Kanu C, Coskun T, Hartman ML, Mao H, Stefanski A, Thomas MK, Haupt A, Robins DA, Du Y. Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study. Appetite VAS + Eating Inventory substudy of Rosenstock 2023. n=275 T2D adults at weeks 24 and 36. Retatrutide ≥4 mg reduced overall appetite, hunger, prospective food consumption vs placebo (p<0.05). EI Perceived Hunger and Disinhibition improved at reta 8/12 mg. Reductions in Perceived Hunger and Disinhibition + increases in Dietary Restraint correlated with weight loss (r = 0.28, 0.36, 0.31). Diabetes Obes Metab. 2025. PMID: 40916752.
  7. 7.Giblin K, Kanu C, Mao H, Thomas MK, Stefanski A, Mather KJ, Du Y, Haupt A, Robins DA. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials program. Design paper for the registrational TRIUMPH Phase 3 program. TRIUMPH-2 is the dedicated T2D Phase 3 trial (ClinicalTrials.gov NCT05929079), Active-Not-Recruiting with estimated completion May 2026 as of verification date 2026-05-25. No Phase 3 T2D readout published yet. Diabetes Obes Metab. 2026. PMID: 41090431.
  8. 8.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 (SURPASS-2). 40-week phase 3, n=1879. Tirzepatide HbA1c reductions -2.01 / -2.24 / -2.30 percentage points (5/10/15 mg) vs -1.86 on semaglutide 1 mg. Body-weight treatment differences vs semaglutide -1.9 / -3.6 / -5.5 kg. The FDA-approved triple-class precedent comparator for T2D. N Engl J Med. 2021. PMID: 34170647.
  9. 9.Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, Cui X, Karanikas CA, Thieu VT. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. 40-week monotherapy trial in drug-naive T2D adults; n=478. HbA1c reductions -1.87% / -1.89% / -2.07% (tirz 5/10/15 mg) vs +0.04% placebo (all P<0.0001). Provides the monotherapy benchmark for the FDA-approved dual GIP/GLP-1 agonist. Lancet. 2021. PMID: 34186022.
  10. 10.Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A; SUSTAIN 7 Investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. 40-week phase 3b, n=1201. Sema 0.5 mg -1.5% vs dula 0.75 mg -1.1% HbA1c (ETD -0.40); sema 1.0 mg -1.8% vs dula 1.5 mg -1.4% (ETD -0.41); both P<0.0001. Weight: sema 1.0 mg -6.5 kg vs dula 1.5 mg -3.0 kg (P<0.0001). Closest GLP-1-only comparator scaffold for understanding what dulaglutide 1.5 mg looks like alongside retatrutide in Rosenstock 2023. Lancet Diabetes Endocrinol. 2018. PMID: 29397376.

Glossary references

Key terms in this article, linked to their canonical definitions.

Important disclaimer. This article is educational information only — not medical advice and not a substitute for consultation with a licensed prescriber. Retatrutide (LY3437943) is an investigational compound. It is NOT FDA-approved for type 2 diabetes or for any other indication, anywhere worldwide as of May 2026. Treatment decisions for type 2 diabetes must be made with a licensed prescriber using FDA-approved medications. Every regulatory and clinical claim in this article is anchored to a primary source (peer-reviewed PubMed literature with verified PMIDs or ClinicalTrials.gov / DailyMed records verified live on 2026-05-25). Weight Loss Rankings does not prescribe, dispense, or endorse any specific medication or pharmacy.