Evidence reference only. Not medical advice, not a dosing guide, and not a recommendation to use any drug.
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Investigational and unapproved. Findings below describe what trials and reports have observed. Nothing here is an endorsement, a claim of safety or effectiveness, or a clinical recommendation.

Retatrutide

INVESTIGATIONAL

GIP, GLP-1 and glucagon receptor triple agonist

52
graded results
8
ongoing records
20
effect domains
Evidence spread
High evidence 2Moderate evidence 44Low evidence 1Very low evidence 5

Retatrutide is investigational in the scoped programme below. Study records do not establish approval, safety or personal suitability. Results describe observations and do not provide treatment advice.

Dated status sources

INVESTIGATIONAL Global programme; Obesity, type 2 diabetes and related complications; Subcutaneous injection; as of 2026-07-13. Eli Lilly and Company

The grade rates how strong the evidence is, not how good or safe the drug is. A low or very-low grade means the evidence is thin, not that an effect is harmful or ruled out.

Retatrutide INVESTIGATIONAL
safety-other Decrease
Moderate evidence

In the JCEM metabolite substudy of the two phase-2 retatrutide trials, retatrutide lowered circulating uric acid dose-dependently versus baseline and placebo,...

Pearson SM et al., J Clin Endocrinol Metab 2026 (metabolomics); PubMed null result 2026 (... Source
Full findingIn the JCEM metabolite substudy of the two phase-2 retatrutide trials, retatrutide lowered circulating uric acid dose-dependently versus baseline and placebo, consistent with the weight-mediated class pattern.
PopulationRetatrutide phase-2 obesity + T2D metabolomics substudy (Pearson et al., post hoc of NCT04881760 / NCT05929066).
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
safety-other Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2a MASLD trial (Sanyal 2024) did not report any uric-acid or gout endpoint.

Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-as... Source
PopulationRetatrutide phase-2a MASLD substudy (Sanyal et al., NCT04881760); reviewed for any uric-acid/gout endpoint - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
safety-other Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2 obesity trial (Jastreboff 2023) did not report any uric-acid or gout endpoint; the only retatrutide urate data come from the...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingEXPLICIT ABSENCE: the retatrutide phase-2 obesity trial (Jastreboff 2023) did not report any uric-acid or gout endpoint; the only retatrutide urate data come from the separate JCEM metabolite substudy.
PopulationRetatrutide phase-2 obesity trial (Jastreboff et al., NCT04881760); reviewed for any uric-acid/gout endpoint - none present in the trial report.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
safety-other Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2a MASLD trial did not report any iron, ferritin, hepcidin, anaemia or haemoglobin endpoint; its biomarker panel was...

Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-as... Source
Full findingEXPLICIT ABSENCE: the retatrutide phase-2a MASLD trial did not report any iron, ferritin, hepcidin, anaemia or haemoglobin endpoint; its biomarker panel was ALT/AST/FIB-4/K-18/ELF/pro-C3 and no iron variable appears anywhere, including the adverse-event table.
PopulationRetatrutide phase-2a MASLD substudy (Sanyal et al., NCT04881760); reviewed for iron/ferritin/hepcidin/anaemia/haemoglobin reporting - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
safety-other Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2 obesity trial did not report any iron, ferritin, hepcidin or anaemia endpoint; its adverse events were gastrointestinal plus...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingEXPLICIT ABSENCE: the retatrutide phase-2 obesity trial did not report any iron, ferritin, hepcidin or anaemia endpoint; its adverse events were gastrointestinal plus a dose-dependent heart-rate increase only, with no iron variable reported.
PopulationRetatrutide phase-2 obesity trial (Jastreboff et al., NCT04881760); reviewed for iron/ferritin/hepcidin/anaemia reporting - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
safety-other Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2 obesity trial did not report any non-iron micronutrient (vitamin D/B12/folate/magnesium/calcium) endpoint - no retatrutide...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingEXPLICIT ABSENCE: the retatrutide phase-2 obesity trial did not report any non-iron micronutrient (vitamin D/B12/folate/magnesium/calcium) endpoint - no retatrutide micronutrient effect can be asserted or excluded.
PopulationRetatrutide phase-2 obesity trial (Jastreboff et al., NCT04881760); reviewed for any non-iron micronutrient (vitamin D/B12/folate/Mg/Ca) endpoint - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
safety-other Mixed
Moderate evidence

RETATRUTIDE DIRECT SAFETY position: across the two phase-2 trials the profile is GI-DOMINANT + a DOSE-DEPENDENT HEART-RATE rise, with NO MTC/pancreatitis/NAION/biliary...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingRETATRUTIDE DIRECT SAFETY position: across the two phase-2 trials the profile is GI-DOMINANT + a DOSE-DEPENDENT HEART-RATE rise, with NO MTC/pancreatitis/NAION/biliary events reported - but these are SHORT (36-48 wk), small per-arm trials, UNDERPOWERED for rare events, so the absence of a signal is NOT clearance. Reta has NO long-term safety data (phase-3 TRIUMPH ongoing).
PopulationPhase-2: obesity (Jastreboff, n=338, 48 wk, 1-12 mg) + T2D (Rosenstock, n=281, 36 wk, 0.5-12 mg, placebo + dulaglutide).
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
safety-other Increase
Moderate evidence

FOLK-CLAIM VERDICT ('retatrutide-specific dysesthesia / skin tingling-buzzing, in 5-15% of users, not in the other two'): TRUE / CONFIRMED - and it OVERTURNS the prior...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingFOLK-CLAIM VERDICT ('retatrutide-specific dysesthesia / skin tingling-buzzing, in 5-15% of users, not in the other two'): TRUE / CONFIRMED - and it OVERTURNS the prior assumption that this was baseless folk chatter. Dysesthesia is a NAMED, DOSE-DEPENDENT, placebo-differentiated, retatrutide-CLASS-SPECIFIC sensory signal (no GLP-1/GIP equivalent), surfaced by the folk-claims loop and NOT previously in the safety dossier (D6/Thread 14). The lay '5-15%' figure if anything UNDERSTATES the 12 mg rate (~21%). Mechanism is UNPROVEN (a glucagon-receptor effect is the leading hypothesis given dose-dependence + class-specificity; rapid weight loss / B-vitamin / electrolyte contributions are partial confounders at best).
PopulationRetatrutide phase-2 obesity trial (skin hyperesthesia ~7%) + phase-3 TRIUMPH-4 topline (dysesthesia 8.8/20.9% at 9/12 mg); no comparable signal for semaglutide or tirzepatide.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
glycaemic Decrease
High evidence

TRANSCEND-T2D-1, the first phase-3 confirmation: in adults with T2D inadequately controlled by diet and exercise, retatrutide produced graduated, dose-dependent HbA1c...

Bajaj HS et al., Lancet, 2026 Source
Full findingTRANSCEND-T2D-1, the first phase-3 confirmation: in adults with T2D inadequately controlled by diet and exercise, retatrutide produced graduated, dose-dependent HbA1c reductions significantly greater than placebo at 40 weeks, corroborating the phase-2 dose-response. Headline caveats: HbA1c is a SURROGATE (not a hard CV/microvascular outcome), and this is MONOTHERAPY in short-duration (mean 2.5 y), diet-and-exercise-only, placebo-only T2D, so generalisability to established/treated T2D is not established.
PopulationTRANSCEND-T2D-1 (NCT06354660): 537 adults with T2D on diet/exercise only (HbA1c 7.0-9.5%, mean diabetes duration 2.5 y), retatrutide 4/9/12 mg vs placebo; 40-week phase-3 double-blind monotherapy RCT.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
glycaemic Decrease
Moderate evidence

In a phase 2 trial in adults with type 2 diabetes, retatrutide reduced HbA1c and body weight versus both placebo and active comparator dulaglutide 1.5 mg.

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 (retatrutide phase 2 in T2D) Source
PopulationPhase 2 NCT04867785: adults with T2D, USA, randomised double-blind, placebo- and dulaglutide-1.5mg-controlled, 36 wk (24-wk primary).
Fundingindustry - Eli Lilly (disclosed in publication)
Comparatorsplacebo; dulaglutide
Retatrutide INVESTIGATIONAL
glycaemic No change
Moderate evidence

In the phase-2 T2D dose-ranging trial, retatrutide's lowest (0.5 mg) dose produced a measured null - no significant HbA1c or weight separation from placebo - defining...

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 Source
Full findingIn the phase-2 T2D dose-ranging trial, retatrutide's lowest (0.5 mg) dose produced a measured null - no significant HbA1c or weight separation from placebo - defining the bottom of the dose-response.
PopulationPeer-reviewed RCT (measured null)
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
glycaemic Decrease
Moderate evidence

In the phase 2 type 2 diabetes trial, retatrutide produced dose-dependent HbA1c reductions at 24 weeks. Reductions were significantly greater than placebo at all doses...

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 Source
Full findingIn the phase 2 type 2 diabetes trial, retatrutide produced dose-dependent HbA1c reductions at 24 weeks. Reductions were significantly greater than placebo at all doses except 0.5 mg and greater than dulaglutide 1.5 mg at the 8 mg slow-escalation and 12 mg doses; no hypoglycaemia was reported.
PopulationRosenstock phase-2 (NCT04867785): 281 adults with T2D (HbA1c 7.0-10.5%, BMI 25-50), on diet/exercise +/- stable metformin; 36-week double-blind placebo- and dulaglutide-1.5mg-controlled RCT, USA; 24-week primary.
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
glycaemic Decrease
Moderate evidence

CROSS-TRIAL juxtaposition (NOT head-to-head, NOT a non-inferiority test): the bare HbA1c point estimates from three SEPARATE trials are reta 12 mg -2.02 to -2.16%...

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 Source
Full findingCROSS-TRIAL juxtaposition (NOT head-to-head, NOT a non-inferiority test): the bare HbA1c point estimates from three SEPARATE trials are reta 12 mg -2.02 to -2.16% (phase-2), tirzepatide 15 mg -2.30% (SURPASS-2), semaglutide 1.0 mg -1.55% (SUSTAIN-1). The point estimates OVERLAP, but with different populations, baselines, durations and designs the comparison cannot establish non-inferiority or superiority in EITHER direction and NO potency rank-order can be drawn. The only within-trial (true) comparison is reta superior to dulaglutide 1.5 mg (a submaximal dose). Class glycaemic rank-ordering, and whether reta's glucagon arm costs net glycaemia, remain UNESTABLISHED until the registered reta-vs-sema head-to-head (TRANSCEND-T2D-2) reports.
PopulationCROSS-TRIAL juxtaposition: reta phase-2 (N=281, 24-36 wk) vs SURPASS-2 (tirz, N=1879 on metformin, 40 wk) vs SUSTAIN-1 (sema, N=388 drug-naive, 30 wk). Different populations/baselines/durations.
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo; dulaglutide 1.5 mg; tirzepatide (separate trial); semaglutide (separate trial)
Retatrutide INVESTIGATIONAL
glycaemic Decrease
Moderate evidence

Glucagon-offset net-efficacy and glycaemic-ceiling observation (NEUTRAL): no NET glycaemic blunting was observed at any dose (the glycaemic outcome is a combination...

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 Source
Full findingGlucagon-offset net-efficacy and glycaemic-ceiling observation (NEUTRAL): no NET glycaemic blunting was observed at any dose (the glycaemic outcome is a combination result - no per-arm penalty can be observed OR excluded from trial data). There is a directional signal that retatrutide's WEIGHT efficacy outruns its HbA1c efficacy relative to a submaximal-dose pure incretin (at 12 mg, ~8.4x dulaglutide's weight effect but only ~1.5x its HbA1c effect), and HbA1c plateaued across 8-12 mg. Recorded as an observation, NOT a per-receptor decomposition.
PopulationReta phase-2 (NCT04867785), 281 adults with T2D, 36 wk, vs placebo and dulaglutide 1.5 mg.
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
appetite-intake Decrease
Moderate evidence

Retatrutide's ONLY appetite/eating-behaviour data is a prespecified exploratory analysis in T2D (appetite VAS + Eating Inventory) showing reduced appetite, hunger and...

Kanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998 Source
Full findingRetatrutide's ONLY appetite/eating-behaviour data is a prespecified exploratory analysis in T2D (appetite VAS + Eating Inventory) showing reduced appetite, hunger and disinhibition; it has NO craving-specific instrument, NO neuroimaging, and its pivotal obesity trial measured no craving at all. So retatrutide 'food noise' reduction is INFERRED by class analogy, NOT demonstrated.
PopulationPrespecified exploratory analysis of the retatrutide phase-2 T2D trial (n=275, 36 wk); reta 0.5-12 mg vs placebo and dulaglutide 1.5 mg.
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
appetite-intake Decrease
Moderate evidence

In the retatrutide phase 2 T2D trial, pre-specified exploratory Appetite VAS showed retatrutide >=4 mg produced greater reductions in OVERALL appetite vs placebo...

Kanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998 Source
Full findingIn the retatrutide phase 2 T2D trial, pre-specified exploratory Appetite VAS showed retatrutide >=4 mg produced greater reductions in OVERALL appetite vs placebo (dose-dependent); the 0.5 mg group did not differ from placebo. First direct retatrutide appetite readout (in adults with T2D specifically).
PopulationAdults with T2D, n=275 efficacy set, phase 2
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
appetite-intake Mixed
Moderate evidence

In the same retatrutide phase 2 T2D appetite analysis, individual VAS items moved heterogeneously: HUNGER fell vs placebo and PROSPECTIVE FOOD CONSUMPTION fell vs...

Kanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998 Source
Full findingIn the same retatrutide phase 2 T2D appetite analysis, individual VAS items moved heterogeneously: HUNGER fell vs placebo and PROSPECTIVE FOOD CONSUMPTION fell vs placebo, but SATIETY and FULLNESS showed NO significant retatrutide-vs-placebo difference at any timepoint over 36 weeks.
PopulationAdults with T2D, phase 2, over 36 weeks
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
appetite-intake Decrease
Moderate evidence

In the retatrutide phase 2 T2D Three-Factor Eating Inventory, higher doses reduced Perceived Hunger and Disinhibition and increased Dietary Restraint; retatrutide 12...

Kanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998 Source
Full findingIn the retatrutide phase 2 T2D Three-Factor Eating Inventory, higher doses reduced Perceived Hunger and Disinhibition and increased Dietary Restraint; retatrutide 12 mg also beat the dulaglutide arm on Perceived Hunger and Disinhibition at Week 36. No dietary calorie-intake records were collected, so no measured intake exists for retatrutide.
PopulationAdults with T2D, phase 2
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
appetite-intake Not directional
Very low evidence

FOLK-CLAIM VERDICT ('appetite/food noise comes ROARING BACK on retatrutide, on treatment'): UNPROVEN. The self-report SIGNAL is real (a striking, oft-repeated...

Self-Reported Side Effects Among Reddit Users Taking Unapproved Retatrutide. medRxiv 2026... Source
Full findingFOLK-CLAIM VERDICT ('appetite/food noise comes ROARING BACK on retatrutide, on treatment'): UNPROVEN. The self-report SIGNAL is real (a striking, oft-repeated observation), but the causal claim is unsupported: (1) the only source is a non-peer-reviewed Reddit text-mining preprint of an unregulated grey-market population (selection/recall/dosing-error/contamination bias); (2) no controlled trial shows paradoxical on-treatment increased appetite; (3) the proposed 'glucagon' mechanism is BACKWARDS - glucagon-receptor agonism SUPPRESSES appetite. Plausibly explained by inconsistent grey-market dosing, normal physiological hunger as the body nears a new set-point, or reporting artefact. NOTE: distinct from the REAL post-discontinuation appetite rebound (D4).
PopulationNon-peer-reviewed medRxiv Reddit text-mining preprint (grey-market reta users); contrasted with the reta phase-2 trial AE profile.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Retatrutide INVESTIGATIONAL
body-composition Decrease
Moderate evidence

Retatrutide phase-2 T2D DXA substudy: fat mass fell dose-dependently; the lean-mass conclusion is a SECONDARY, proportional-only claim ('proportion of lean-mass loss...

Coskun T et al. (Eli Lilly), Lancet Diabetes Endocrinol, 2025 Source
Full findingRetatrutide phase-2 T2D DXA substudy: fat mass fell dose-dependently; the lean-mass conclusion is a SECONDARY, proportional-only claim ('proportion of lean-mass loss similar to other obesity treatments'), read by the sponsor as reassurance. CRITICAL: no ABSOLUTE lean-kg is reported, and proportional parity at a larger total loss is fully compatible with the LARGEST absolute lean-kg loss of any agent. Completer-only, T2D, fat-primary endpoint.
PopulationSubstudy of the retatrutide phase-2 T2D RCT (NCT04867785), double-blind placebo- and dulaglutide-controlled; 189 enrolled to substudy, 103 with paired baseline+week-36 DXA (completer-only); DXA at week 36.
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide
Retatrutide INVESTIGATIONAL
body-composition Decrease
Moderate evidence

Phase 2a MASLD substudy used MRI-PDFF to quantify hepatic fat alongside body-composition assessment; retatrutide markedly reduced liver fat content (ectopic-fat depot...

Sanyal AJ et al., triple agonist retatrutide for MASLD, Nat Med, 2024 Source
Full findingPhase 2a MASLD substudy used MRI-PDFF to quantify hepatic fat alongside body-composition assessment; retatrutide markedly reduced liver fat content (ectopic-fat depot adjacent to body-composition remit).
PopulationPre-specified substudy of phase 2 obesity trial, participants with MASLD; MRI-PDFF
Fundingindustry - Eli Lilly (disclosed; retatrutide MASLD substudy)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
body-composition Not directional
Moderate evidence

Retatrutide's phase 2 obesity trial reported body weight but no DXA or other body-composition measurement, so absolute lean-mass change at the 12 mg dose is unknown....

Gap row derived from absence across the retatrutide phase-2 reports (PMID 37366315 weight... Source
Full findingRetatrutide's phase 2 obesity trial reported body weight but no DXA or other body-composition measurement, so absolute lean-mass change at the 12 mg dose is unknown. The reported retatrutide DXA evidence comes from a type 2 diabetes substudy with less total weight loss, and no reported retatrutide trial has measured muscle strength or physical function. The glucagon-receptor component provides a mechanistic reason to study amino-acid and muscle effects directly, but does not establish excess lean-mass loss. Both the amount and clinical significance of lean-mass change during higher-magnitude retatrutide weight loss therefore remain uncertain.
PopulationRetatrutide programme to date: phase-2 obesity (Jastreboff, NEJM 2023, PMID 37366315, weight only) and phase-2 T2D DXA substudy (Coskun, Lancet D&E 2025, PMID 40609566, fat-mass primary); no function endpoint in any reported reta trial.
Fundingacademic - Canadian Institutes for Health Research (CIHR grant 154321), Drucker review
Comparatorsplacebo; dulaglutide
Retatrutide INVESTIGATIONAL
body-composition Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2a MASLD trial (Sanyal 2024) did not report any DXA/BMD, bone-turnover or fracture endpoint.

Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-as... Source
PopulationRetatrutide phase-2a MASLD substudy (Sanyal et al., NCT04881760); reviewed for any DXA/BMD/bone-turnover/fracture endpoint - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
body-composition Not directional
Moderate evidence

EXPLICIT ABSENCE: the retatrutide phase-2 obesity trial (Jastreboff 2023) did not report any DXA/BMD, bone-turnover or fracture endpoint - no retatrutide bone effect...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingEXPLICIT ABSENCE: the retatrutide phase-2 obesity trial (Jastreboff 2023) did not report any DXA/BMD, bone-turnover or fracture endpoint - no retatrutide bone effect can be asserted or excluded; all retatrutide bone inference is indirect class-extrapolation.
PopulationRetatrutide phase-2 obesity trial (Jastreboff et al., NCT04881760); reviewed for any DXA/BMD/bone-turnover/fracture endpoint - none present in the trial report.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
insulin-beta-cell Decrease
Moderate evidence

Higher retatrutide doses reduced biomarkers of insulin resistance (fasting insulin, fasting C-peptide and HOMA2-IR) by up to 50% or more from baseline — a combination...

Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-as... Source
Full findingHigher retatrutide doses reduced biomarkers of insulin resistance (fasting insulin, fasting C-peptide and HOMA2-IR) by up to 50% or more from baseline — a combination and weight-mediated effect not isolable per receptor.
PopulationMASLD substudy of phase 2 obesity trial (NCT04881760)
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
insulin-beta-cell Decrease
Moderate evidence

No study indexed under these search terms as of 2026 has performed a hyperinsulinaemic-euglycaemic clamp or stable-isotope endogenous-glucose-production tracer study...

Pearson SM et al., J Clin Endocrinol Metab 2026 (metabolomics); PubMed null result 2026 (... Source
Full findingNo study indexed under these search terms as of 2026 has performed a hyperinsulinaemic-euglycaemic clamp or stable-isotope endogenous-glucose-production tracer study under retatrutide; the drug-level decomposition of net glycaemic benefit into insulin secretion, glucagon suppression and hepatic-clearance-driven insulin sensitivity remains unmeasured directly. A post-hoc metabolomic analysis of both phase 2 trials found retatrutide shifted an insulin-resistance metabolite signature (BCAAs, 2-aminoadipic acid, 2-hydroxybutyrate, urate, short-chain/saturated triglycerides) toward improved metabolic health.
PopulationHumans; PubMed null + post-hoc metabolomics (obesity n=282, T2D n=213)
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
insulin-beta-cell Not directional
Moderate evidence

The retatrutide phase 2 type 2 diabetes trial reported HbA1c, fasting glucose, weight and tolerability but no direct beta-cell-function measure, and no indexed...

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 Source
Full findingThe retatrutide phase 2 type 2 diabetes trial reported HbA1c, fasting glucose, weight and tolerability but no direct beta-cell-function measure, and no indexed retatrutide study reporting one was identified. Available insulin-axis measurements are insulin-resistance biomarkers rather than secretion or beta-cell-function readouts. Because retatrutide also produced substantial weight loss, any future beta-cell signal would require a design capable of separating weight-mediated from direct effects. Its glucagon-receptor activity is an additional reason to obtain direct measurements, not evidence of beta-cell harm. Whether retatrutide improves beta-cell function therefore remains unknown.
PopulationReta phase-2 T2D (Rosenstock, Lancet 2023, NCT04867785), N=281; plus a null PubMed search for reta beta-cell secretion/function as of 2026.
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo; dulaglutide 1.5 mg
Retatrutide INVESTIGATIONAL
insulin-beta-cell Decrease
Low evidence

In phase 1, fasting glucagon decreased under retatrutide from 24 h to day 15 at 4.5/6 mg, while fasting-glucose changes were similar to placebo — net neutrality on...

Coskun T et al. phase 1 SAD, as restated in Biomolecules 2025 review (PMC12190491) Source
Full findingIn phase 1, fasting glucagon decreased under retatrutide from 24 h to day 15 at 4.5/6 mg, while fasting-glucose changes were similar to placebo — net neutrality on fasting glucose despite an engaged glucagon arm (the glucagon-offset in action at the drug level). Whether the glucagon fall reflects GLP-1R glucagonostasis, weight loss, improved glycaemia, or direct islet effects is unresolved.
PopulationPhase 1 SAD, humans
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
lipids-lipoprotein Decrease
Moderate evidence

Retatrutide produced strong dose-dependent triglyceride and LDL lowering in phase 2 obesity (glucagon-agonism-enhanced lipid effect).

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
PopulationN=338 adults with obesity; retatrutide 1-12 mg vs placebo; 48 weeks; phase 2 (NCT04881760).
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
lipids-lipoprotein Decrease
Moderate evidence

In post-hoc analyses of two phase-2 retatrutide trials, circulating ANGPTL3/8 complex concentrations fell dose-dependently and these decreases paralleled the...

Wen Y, Lemen D, ... Konrad RJ, Diabetes Obes Metab 2025;27(10):5985-5995 Source
Full findingIn post-hoc analyses of two phase-2 retatrutide trials, circulating ANGPTL3/8 complex concentrations fell dose-dependently and these decreases paralleled the retatrutide-induced reductions in triglycerides and LDL-C.
PopulationPost-hoc analysis of two phase-2 retatrutide RCTs: participants with type 2 diabetes and participants with obesity/overweight without diabetes; ANGPTL3/8 measured by dedicated immunoassay from baseline.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
lipids-lipoprotein Decrease
Moderate evidence

In the phase-2a MASLD substudy, retatrutide was associated with a significant reduction in fasting triglycerides (and improved insulin-sensitivity markers); the paper...

Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-as... Source
Full findingIn the phase-2a MASLD substudy, retatrutide was associated with a significant reduction in fasting triglycerides (and improved insulin-sensitivity markers); the paper additionally cites improvements in non-HDL cholesterol from other retatrutide trials in people with type 2 diabetes or obesity.
PopulationPhase-2a MASLD substudy of the retatrutide obesity phase-2 trial (NCT04881760); N=98 adults with obesity and MASLD (>=10% liver fat); retatrutide 1-12 mg vs placebo; 48 weeks.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
weight-loss Decrease
High evidence

In retatrutide's first phase-3 trial, monotherapy produced 11.5-15.3% weight loss in type-2 diabetes; the glycaemic arm (HbA1c) is recorded separately...

Bajaj HS et al., Lancet, 2026 Source
Full findingIn retatrutide's first phase-3 trial, monotherapy produced 11.5-15.3% weight loss in type-2 diabetes; the glycaemic arm (HbA1c) is recorded separately (C2-RETATRUTIDE-GLY-02).
PopulationTRANSCEND-T2D-1 (NCT06354660): 537 adults with type-2 diabetes inadequately controlled by diet and exercise, retatrutide 4/9/12 mg vs placebo 1:1:1:1; 40-week phase-3 randomised double-blind placebo-controlled monotherapy RCT at 48 sites (USA/Mexico/India).
Fundingindustry-Eli Lilly
Retatrutide INVESTIGATIONAL
weight-loss Decrease
Moderate evidence

Triple GIP/GLP-1/glucagon agonist (LY3437943, Eli Lilly). In phase 2 obesity, once-weekly s.c. retatrutide produced large dose-dependent weight loss; phase 3 TRIUMPH...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingTriple GIP/GLP-1/glucagon agonist (LY3437943, Eli Lilly). In phase 2 obesity, once-weekly s.c. retatrutide produced large dose-dependent weight loss; phase 3 TRIUMPH subsequently reported weight loss up to ~29% at 68 weeks. Balanced agonist at GIPR, GLP-1R and GCGR, the glucagon arm proposed to add an energy-expenditure component atop incretin-driven appetite suppression.
PopulationPhase 2 NCT04881760: N=338 adults, BMI >=30 or 27-<30 with weight-related condition, 48 wk, placebo-controlled. TRIUMPH-4 NCT05931367: phase 3, 68 wk, obesity + knee OA. TRIUMPH-1: phase 3, 80 wk, obesity/overweight.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
weight-loss Decrease
Very low evidence

Eli Lilly's TRIUMPH-1 phase 3 topline press release reported weight loss of up to 28.3% at 80 weeks with retatrutide 12 mg, with 45.3% of participants losing at least...

Eli Lilly, TRIUMPH-1 (retatrutide) Phase 3 topline press release, PRNewswire, 21 May 2026... Source
Full findingEli Lilly's TRIUMPH-1 phase 3 topline press release reported weight loss of up to 28.3% at 80 weeks with retatrutide 12 mg, with 45.3% of participants losing at least 30%; the high-BMI extension reported up to 30.3% at 104 weeks. These sponsor-announced results were not peer reviewed or posted as registry results at the catalogue date. The release reported no DXA, energy-expenditure or receptor-specific data, so it informs weight-loss efficacy rather than mechanism.
PopulationTRIUMPH-1 (NCT05929066): n=2,339, obesity without diabetes, 80 weeks +/- high-BMI extension to 104 weeks
Fundingindustry - Eli Lilly (trial sponsor; corporate topline announcement of its own TRIUMPH-1 trial)
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Head-to-head comparisons Increase
Moderate evidence

Phase 2 obesity, placebo-controlled (no GLP-1/dual active comparator). Retatrutide 48-week weight loss -8.7% (1 mg), -17.1% (4 mg), -22.8% (8 mg), -24.2% (12 mg) vs...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingPhase 2 obesity, placebo-controlled (no GLP-1/dual active comparator). Retatrutide 48-week weight loss -8.7% (1 mg), -17.1% (4 mg), -22.8% (8 mg), -24.2% (12 mg) vs placebo -2.1%. Responder rates at 12 mg: 100% >=5%, 93% >=10%, 83% >=15%. This is the source of the cited '~24% phase 2' top rung of the efficacy ladder.
Population338 adults with obesity (or BMI 27-30 + complication), double-blind placebo-controlled phase 2, 48 weeks
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
Head-to-head comparisons Increase
Moderate evidence

DIRECT head-to-head (phase 2 T2D): retatrutide vs dulaglutide 1.5 mg active comparator. At 36 weeks, retatrutide 8-12 mg gave HbA1c reductions (-1.99 to -2.02 pp at 24...

Rosenstock J, Frias J, Jastreboff AM, et al. Lancet 2023 Source
Full findingDIRECT head-to-head (phase 2 T2D): retatrutide vs dulaglutide 1.5 mg active comparator. At 36 weeks, retatrutide 8-12 mg gave HbA1c reductions (-1.99 to -2.02 pp at 24 wk) significantly GREATER than dulaglutide 1.5 mg (-1.41 pp; p=0.0019 to 0.0002 for the higher doses). Weight at 36 weeks: reta up to -16.94% (12 mg) vs dulaglutide -2.02% (all reta >=4 mg p<0.0001 vs dula).
Population281 adults with T2D (HbA1c 7-10.5%, BMI 25-50), double-blind, placebo- AND active-comparator (dulaglutide 1.5 mg), 36 weeks
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo; dulaglutide 1.5 mg
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Heart and circulation Not directional
Moderate evidence

OPEN QUESTION: no outcome trial isolates a glucagon (GCGR) arm, so the net CV-OUTCOME consequence of glucagon agonism is unresolved. The concern, whether...

Absence established via PubMed sweep (2026-06-21): no dual-agonist CV-outcome-trial recor... Source
Full findingOPEN QUESTION: no outcome trial isolates a glucagon (GCGR) arm, so the net CV-OUTCOME consequence of glucagon agonism is unresolved. The concern, whether glucagon-driven sustained heart-rate elevation or increased cardiac workload could ERODE the CV benefit established for GLP-1 (with the GIP-containing dual agonist shown CV-safe at whole-molecule level via SURPASS-CVOT, GIP not isolated), is recorded as a tension to be settled by retatrutide's outcome programme, not as a quantified finding.
PopulationNo isolating trial exists. The only dedicated triple-agonist CVOT is TRIUMPH-Outcomes (NCT06383390), hard endpoints ~2029.
Fundingacademic / non-commercial (De Fano GIP review; no industry sponsor; disclosed)
Retatrutide INVESTIGATIONAL
Heart and circulation Not directional
Moderate evidence

The retatrutide phase-2 trial produced NO hard CV-outcome data; MACE and CV death were not endpoints. Its heart-rate rise is a CV-mechanism signal held in the...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingThe retatrutide phase-2 trial produced NO hard CV-outcome data; MACE and CV death were not endpoints. Its heart-rate rise is a CV-mechanism signal held in the heart-rate / CV-mechanism thread, deliberately not counted in the cv-outcomes domain to avoid double-counting.
PopulationJastreboff AM et al. phase-2 (NCT04881760): N=338 adults with obesity (entry BMI-based: >=30, or 27-30 with a weight-related condition); retatrutide vs placebo, 48 weeks; double-blind RCT.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Heart rate Increase
Moderate evidence

Retatrutide caused dose-dependent HR increases peaking at 24 weeks then declining; the largest HR signal observed in the class, with a flagged arrhythmia caution.

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
PopulationN=338 adults with obesity; retatrutide 1-12 mg vs placebo; 48 weeks; phase 2 (NCT04881760).
Fundingindustry-Eli Lilly
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
Heart rate Increase
Very low evidence

In isolated mouse right atria, retatrutide itself exerted positive chronotropy that was antagonised by the GCGR antagonist adomeglivant, potentiated by rolipram (PDE4...

Neumann J et al., Naunyn Schmiedebergs Arch Pharmacol 2025;398(12):17147-17160 Source
Full findingIn isolated mouse right atria, retatrutide itself exerted positive chronotropy that was antagonised by the GCGR antagonist adomeglivant, potentiated by rolipram (PDE4 inhibition) and abolished by the PKA inhibitor H89 - but NOT weakened by propranolol; the authors conclude retatrutide excites beating rate via GCGR, signalling through cAMP/PKA.
Populationisolated mouse right atria (and left atria for force of contraction)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Comparatorsadomeglivant; rolipram; H89; propranolol
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
energy-expenditure-thermogenesis Increase
Moderate evidence

FOLK-CLAIM VERDICT ('retatrutide runs hot / sweating / feels hot, via glucagon'): MIXED - the MECHANISM is real and plausibly reta-distinct (glucagon thermogenesis is...

Salem V et al. Glucagon increases energy expenditure independently of brown adipose tissu... Source
Full findingFOLK-CLAIM VERDICT ('retatrutide runs hot / sweating / feels hot, via glucagon'): MIXED - the MECHANISM is real and plausibly reta-distinct (glucagon thermogenesis is textbook human physiology, and reta is the only glucagon-arm agent in late development), but the reta-DIRECT evidence is thin-to-absent (no controlled thermometry/sweating measurement; not a prominent named AE in phase-2). So the 'runs hot' symptom is INFERRED from the mechanism, not demonstrated in patients.
PopulationHuman glucagon-infusion thermogenesis study (Salem 2016) for the mechanism; reta phase-2 obesity/T2D trials (no temperature endpoint) for the direct-data gap.
Fundingacademic-MRC/BBSRC/NIHR/Wellcome Trust
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
energy-expenditure-thermogenesis Not directional
Very low evidence

Glucagon-mediated increased energy expenditure is PROPOSED for retatrutide (mechanistic/preclinical reviews); not measured in the cited human phase-2 trial.

Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-Hormone-Receptor Agonist Retatrutide fo... Source
PopulationPreclinical (rodent) models with calorie-intake-matched controls; reported via reviews/secondary sources
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Comparatorscalorie-intake-matched control
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Liver and MASH Decrease
Moderate evidence

In a phase 2a MASLD substudy, retatrutide produced very large reductions in liver fat with a high proportion of participants reaching normal liver-fat content.

Sanyal AJ et al., triple agonist retatrutide for MASLD, Nat Med, 2024 Source
PopulationN=98 adults with obesity and elevated liver fat (MASLD), substudy of phase 2 obesity trial NCT04881760, retatrutide 1/4/8/12 mg vs placebo, 48 wk.
Fundingindustry - Eli Lilly (disclosed; retatrutide MASLD substudy)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
Liver and MASH Decrease
Moderate evidence

In the published phase-2a MASLD substudy of the reta obesity phase-2 trial, retatrutide produced large dose-dependent MRI-PDFF liver-fat reductions at 24 wk with a...

Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-as... Source
Full findingIn the published phase-2a MASLD substudy of the reta obesity phase-2 trial, retatrutide produced large dose-dependent MRI-PDFF liver-fat reductions at 24 wk with a high proportion reaching normal liver fat. CRITICAL SCOPE LIMIT: the endpoint was liver FAT (steatosis) by MRI-PDFF, an IMAGING SURROGATE; the substudy included NO liver biopsy and assessed NEITHER MASH resolution NOR fibrosis. Reta therefore has NO histological MASH or fibrosis outcome data.
Populationn=98 adults with obesity, MASLD and >=10% liver fat (substudy of the 48-wk obesity phase-2); double-blind placebo-controlled; reta 1/4/8/12 mg vs placebo; primary at 24 wk.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
blood-pressure Decrease
Moderate evidence

Retatrutide lowered SBP/DBP dose-dependently (exploratory) in phase 2 obesity.

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
PopulationN=338 adults with obesity; retatrutide 1-12 mg vs placebo; 48 weeks; phase 2 (NCT04881760).
Fundingindustry-Eli Lilly
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
renal Mixed
Moderate evidence

Pooled post hoc of two phase 2 trials: higher-dose retatrutide reduced UACR in T2D and obesity, and increased eGFR in obesity but not in T2D.

Heerspink HJL et al. (retatrutide kidney), Kidney Int Rep, 2025;10:1980-1992 Source
PopulationPooled post hoc, 2 phase 2 RCTs; T2D n=281 (wk36, dula comparator) and obesity n=338 (wk48); eGFR >=45.
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg (T2D study)
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Stomach and gut Increase
Moderate evidence

GI AEs most common, dose-related, mostly mild-to-moderate; partially mitigated by a lower 2 mg (vs 4 mg) starting dose. Nausea showed a clear dose gradient.

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
PopulationRetatrutide phase 2: 338 adults with obesity; 48 weeks; phase 2 RCT
Fundingindustry-Eli Lilly
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Brain and mood Not directional
Moderate evidence

RETATRUTIDE GAP: retatrutide has essentially NO dedicated CNS, addiction, cognition or psychiatric data beyond routine adverse-event capture in its two phase-2 trials....

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingRETATRUTIDE GAP: retatrutide has essentially NO dedicated CNS, addiction, cognition or psychiatric data beyond routine adverse-event capture in its two phase-2 trials. The absence is the finding. Any class CNS effect attributed to retatrutide is a class-transfer expectation, not a reta result - and reta's GLUCAGON arm (central glucagon/energy-balance/mood circuitry) is a CNS-relevant differentiator that is entirely unstudied, so even the class transfer may not capture it. Central glucagon circuitry intersects mood/satiety/stress pathways and could move neuropsychiatric outcomes in EITHER direction - the sign is UNKNOWN, not presumed benign. Routine adverse-event capture in the phase-2 trials is NOT a psychiatric-safety clearance for retatrutide, only an absence of dedicated data.
PopulationReta phase-2 obesity (Jastreboff, NCT04881760, N=338) + T2D (Rosenstock, NCT04867785, N=281); psychiatric AEs captured only as routine treatment-emergent events, not instrumented.
Fundingindustry-Eli Lilly
Comparatorsplacebo; dulaglutide 1.5 mg
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
weight-maintenance-regain Not directional
Moderate evidence

RETATRUTIDE GAP: no maintenance, withdrawal/regain or intermittent-dosing data specific to retatrutide exist. The phase-2 obesity trial reported continuous...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingRETATRUTIDE GAP: no maintenance, withdrawal/regain or intermittent-dosing data specific to retatrutide exist. The phase-2 obesity trial reported continuous on-treatment loss to 48 weeks (up to -24.2%) with weight still declining at trial end, but contained NO withdrawal or off-treatment arm. Reta's regain kinetics are UNKNOWN and must be inferred from the GLP-1/GIP class - a CLASS-TRANSFER expectation (reta would be expected to regain like the class), NOT a reta result. The steep, non-plateauing curve concerns the CEILING of loss, NOT regain kinetics; the proportion and absolute magnitude of any reta regain are UNQUANTIFIED and untested. Reta's glucagon arm (an energy-expenditure component absent from the GLP-1/GIP class) makes the class-transfer NON-AUTOMATIC in mechanism as well as magnitude - its off-treatment behaviour cannot be assumed to track a pure incretin in either direction. If regain is disproportionately fat (the C-CLASS-MAINT-04 gap), the agent that loses the most is the one whose loss-regain cycle could most degrade the lean:fat ratio (cross-ref D2) - the highest-stakes, untested instance of that gap.
PopulationReta phase-2 obesity (Jastreboff, NEJM 2023, NCT04881760): N=338; 48 weeks on-treatment; no withdrawal arm.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
pharmacology Not directional
Moderate evidence

EXPLICIT ABSENCE: there is no retatrutide gut-microbiome data of any kind - human or animal. Unlike liraglutide and semaglutide (rodent + small human compositional...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingEXPLICIT ABSENCE: there is no retatrutide gut-microbiome data of any kind - human or animal. Unlike liraglutide and semaglutide (rodent + small human compositional studies), retatrutide's microbiome effects are a complete void, not a measured-null, and cannot be inferred from its weight-loss data.
PopulationRetatrutide evidence base reviewed for any gut-microbiome indication (pinned to the phase-2 obesity trial, Jastreboff et al., NCT04881760, as the reviewed-for-indication anchor) - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Sleep apnoea Not directional
Very low evidence

RETATRUTIDE-DIRECT OSA POSITION: reta has no published OSA/AHI outcome data. Its OSA relevance rests on (a) the registrational TRIUMPH OSA endpoints (results pending)...

Position derived from TRIUMPH design (Giblin K et al., Diabetes Obes Metab 2025, PMID 410...
Full findingRETATRUTIDE-DIRECT OSA POSITION: reta has no published OSA/AHI outcome data. Its OSA relevance rests on (a) the registrational TRIUMPH OSA endpoints (results pending) and (b) the inference that, because OSA benefit in this class appears largely weight-mediated, the agent with the largest weight loss should deliver the largest AHI reduction. Stated as an EXPECTATION conditional on weight-mediation - not an outcome reta has demonstrated.
Populationn/a (positional/inferential row). Weight-loss anchor: reta phase-2 (Jastreboff 2023, obesity, 48 wk) up to ~24% mean weight loss (weight-loss domain).
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Retatrutide INVESTIGATIONAL
Specific groups of people Not directional
Moderate evidence

EXPLICIT ABSENCE: there is no retatrutide data in type-1 diabetes of any kind. Unlike liraglutide (two pivotal RCTs) and tirzepatide (one phase-2 trial), retatrutide...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source
Full findingEXPLICIT ABSENCE: there is no retatrutide data in type-1 diabetes of any kind. Unlike liraglutide (two pivotal RCTs) and tirzepatide (one phase-2 trial), retatrutide has not been studied as an insulin adjunct in T1D - a complete void, not a measured-null.
PopulationRetatrutide evidence base reviewed for any type-1-diabetes indication (pinned to the phase-2 obesity trial, Jastreboff et al., NCT04881760, as the reviewed-for-indication anchor) - none present.
Fundingindustry-Eli Lilly
Comparatorsplacebo

Registered or protocol records without results

These records remain discoverable, but they are not counted or presented as results.

Retatrutide INVESTIGATIONAL
Heart and circulation Not directional REGISTERED, NO RESULTS
Very low evidence

The dedicated retatrutide cardiovascular-outcomes trial, TRIUMPH-Outcomes, is ongoing. No hard-outcome MACE or cardiovascular-death results have been reported, so the...

Eli Lilly, TRIUMPH-Outcomes (ongoing) Source
Full findingThe dedicated retatrutide cardiovascular-outcomes trial, TRIUMPH-Outcomes, is ongoing. No hard-outcome MACE or cardiovascular-death results have been reported, so the registration is not evidence of cardiovascular benefit.
PopulationTRIUMPH-Outcomes (NCT06383390): adults age >=45, BMI >=27, with established ASCVD and/or CKD (HbA1c <=10% if T2D); retatrutide s.c. once weekly (escalated dose) vs placebo; double-blind, event-driven; ~5-year study.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
Heart and circulation Not directional REGISTERED, NO RESULTS
Very low evidence

CLARIFYING NOTE: TRIUMPH-3 (NCT05882045) enrols adults with severe obesity (BMI >=35) AND established CVD, but its primary endpoint is percent change in body weight,...

Eli Lilly. TRIUMPH-3: Phase 3 study of LY3437943 once weekly vs placebo in severe obesity... Source
Full findingCLARIFYING NOTE: TRIUMPH-3 (NCT05882045) enrols adults with severe obesity (BMI >=35) AND established CVD, but its primary endpoint is percent change in body weight, not MACE. It is a weight-loss trial in a CVD population, NOT a CV outcomes trial; the only dedicated reta CV outcomes (MACE) trial is TRIUMPH-Outcomes (NCT06383390).
PopulationTRIUMPH-3: N=1,946; severe obesity (BMI >=35) with established CVD (prior MI, stroke, or symptomatic PAD); retatrutide s.c. once weekly (two doses) vs placebo; Phase 3 double-blind.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
weight-maintenance-regain Not directional REGISTERED, NO RESULTS
Very low evidence

REGISTRY (no results): TRIUMPH-6 (NCT06859268) is the registered phase-3b retatrutide weight-MAINTENANCE trial with a continued-vs-withdrawal (re-randomisation) design...

Eli Lilly. TRIUMPH-6: maintenance of weight reduction with retatrutide. ClinicalTrials.go... Source
Full findingREGISTRY (no results): TRIUMPH-6 (NCT06859268) is the registered phase-3b retatrutide weight-MAINTENANCE trial with a continued-vs-withdrawal (re-randomisation) design - the first reta trial designed to measure maintenance vs withdrawal of weight reduction, i.e. the trial whose future readout would fill the reta regain gap.
PopulationTRIUMPH-6 (NCT06859268): adults with obesity and a history of unsuccessful dietary weight loss, without diabetes; retatrutide lead-in then re-randomise (continue dose 1 / escalate dose 2 / placebo); phase-3b double-blind.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorsplacebo; retatrutide (continued); retatrutide (escalated)
Retatrutide INVESTIGATIONAL
Liver and MASH Not directional REGISTERED, NO RESULTS
Very low evidence

REGISTRATIONAL GAP: no dedicated retatrutide MASH / MASH-with-fibrosis phase-2b or phase-3 histology trial could be identified. PubMed returns no reta histological...

No dedicated reta MASH-histology trial located in PubMed or via trial-registry knowledge ...
Full findingREGISTRATIONAL GAP: no dedicated retatrutide MASH / MASH-with-fibrosis phase-2b or phase-3 histology trial could be identified. PubMed returns no reta histological MASH/steatohepatitis trial, and the reta phase-3 (TRIUMPH) programme targets obesity, T2D, knee osteoarthritis and cardiovascular outcomes - not a biopsy MASH-resolution/fibrosis endpoint. Unlike semaglutide (ESSENCE), tirzepatide (SYNERGY-NASH), survodutide and pemvidutide (IMPACT), reta has no liver-histology registrational trial. Stated as a GAP, not finessed.
Populationn/a - registry/landscape gap statement.
Fundingn/a - absence-of-evidence landscape note (no study, no sponsor)
Retatrutide INVESTIGATIONAL
Sleep apnoea Not directional REGISTERED, NO RESULTS
Very low evidence

The TRIUMPH phase 3 programme includes moderate-to-severe obstructive-sleep-apnoea cohorts with change in apnoea-hypopnoea index as a primary endpoint. Results have...

ClinicalTrials.gov TRIUMPH-1 (NCT05929066) and TRIUMPH-2 (NCT05929079), Eli Lilly; regist... Source
Full findingThe TRIUMPH phase 3 programme includes moderate-to-severe obstructive-sleep-apnoea cohorts with change in apnoea-hypopnoea index as a primary endpoint. Results have not been reported, so this registration does not establish an observed OSA benefit.
PopulationTRIUMPH-1 (NCT05929066): adults without T2D, obesity/overweight, OSA subset AHI >=15 on PSG, N~2335, phase-3 double-blind placebo-controlled, weekly s.c. retatrutide vs placebo. TRIUMPH-2 (NCT05929079): adults with T2D, OSA subset, N~1000.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
glycaemic Not directional REGISTERED, NO RESULTS
Very low evidence

REGISTRY (no results): TRIUMPH-2 (NCT05929079) is a phase-3 master protocol of once-weekly retatrutide in adults with T2D who have obesity/overweight, including an...

Eli Lilly. TRIUMPH-2 master protocol of retatrutide in T2D with obesity/overweight (incl.... Source
Full findingREGISTRY (no results): TRIUMPH-2 (NCT05929079) is a phase-3 master protocol of once-weekly retatrutide in adults with T2D who have obesity/overweight, including an obstructive sleep apnoea (OSA) subset. Confirmed as a reta phase-3 T2D trial; its primary endpoint is body weight (and AHI for the OSA arm), NOT HbA1c, so its glycaemic outcomes are secondary and unreported.
PopulationTRIUMPH-2 (NCT05929079): adults with T2D for >=90 days, BMI >=27, incl. an OSA subset; retatrutide (3 doses) vs placebo; phase-3.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Retatrutide INVESTIGATIONAL
glycaemic Not directional REGISTERED, NO RESULTS
Very low evidence

REGISTRY (no results): NCT06260722 is TRANSCEND-T2D-2, a phase-3 OPEN-LABEL trial of once-weekly retatrutide versus once-weekly semaglutide in adults with T2D...

Eli Lilly. TRANSCEND-T2D-2: retatrutide vs semaglutide in T2D inadequately controlled on ... Source
Full findingREGISTRY (no results): NCT06260722 is TRANSCEND-T2D-2, a phase-3 OPEN-LABEL trial of once-weekly retatrutide versus once-weekly semaglutide in adults with T2D inadequately controlled on metformin +/- an SGLT2 inhibitor, with an HbA1c primary endpoint. This is the within-class HEAD-TO-HEAD that will, for the first time, pit the triple agonist directly against the leading GLP-1 monoagonist on glycaemia - until it reports, every reta-vs-sema glycaemic comparison is cross-trial only.
PopulationTRANSCEND-T2D-2 (NCT06260722): adults with T2D, HbA1c 7.0-10.5%, on stable metformin +/- SGLT2i, BMI >=25; retatrutide (2 doses) vs semaglutide; phase-3 open-label.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Comparatorssemaglutide
Retatrutide INVESTIGATIONAL
glycaemic Not directional REGISTERED, NO RESULTS
Very low evidence

REGISTRY (no results): NCT06297603 is TRANSCEND-T2D-3, a phase-3 double-blind trial of once-weekly retatrutide versus placebo in adults with T2D AND moderate-to-severe...

Eli Lilly. TRANSCEND-T2D-3: retatrutide vs placebo in T2D with renal impairment on basal ... Source
Full findingREGISTRY (no results): NCT06297603 is TRANSCEND-T2D-3, a phase-3 double-blind trial of once-weekly retatrutide versus placebo in adults with T2D AND moderate-to-severe renal impairment, inadequately controlled on basal insulin (+/- metformin and/or SGLT2i), with an HbA1c primary. It IS a reta-vs-placebo T2D trial, but in a renal-impairment, basal-insulin-background subgroup - NOT the generic T2D-vs-placebo cohort the backlog implied.
PopulationTRANSCEND-T2D-3 (NCT06297603): adults with T2D, HbA1c 7.0-10.5%, moderate-to-severe renal impairment, on stable basal insulin +/- metformin and/or SGLT2i; retatrutide (3 doses) vs placebo; phase-3 double-blind.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Comparatorsplacebo