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Ret5.5
Retatrutid – Forschung
Überwiegend Mechanismus / Beobachtung
25 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Retatrutid sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus hochwertigen Meta-Analysen und randomisierten Studien, veröffentlicht 2022–2026 mit einer typischen Studiengröße von 537 Teilnehmenden.
Basierend auf 25 Studien · 5 Meta-Analysen · 8 RCTs · 171,117 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Weight managementIn der 48-wöchigen Phase-2-Adipositasstudie führte die 12-mg-Dosis zu einem mittleren Gewichtsverlust von ~24,2 %; die Phase-3-Bestätigung steht noch aus · Fortschreitend über 24-48 Wochen
Überwiegend Mechanismus / Beobachtung21 Studien
Glucose & glycemic controlDosisabhängige HbA1c-Senkungen bei Typ-2-Diabetes (Höchstdosen ~-2,0 %, besser als Dulaglutid) · Nach 24-36 Wochen · Kombiniert deuten der große Gewichtsverlust, die Leberfettreduktion und die glykämische Kontrolle auf einen breiten metabolischen Nutzen hin (Phase 2) · Nach 24-48 Wochen
Überwiegend Mechanismus / Beobachtung17 Studien
Safety profile
Überwiegend Mechanismus / Beobachtung11 Studien
Liver fat & MASLDIn einer Phase-2a-MASLD-Teilstudie sank der Leberfettgehalt bei 8/12 mg um ~81-82 %; vielversprechend, aber früh, keine Histologie-/Endpunktdaten · Nach 24 Wochen
Zu wenige bewertete Studien2 Studien
Aktives Forschungsgebiet
25 Studien in den letzten 5 Jahren · Neueste Meta-Analyse: 2026
20222026
1Meta-Analysen=977 · large study2026
Incretin-based therapy led to a modest but clinically meaningful BP reduction and lower all-cause mortality in adults with overweight or obesity, without excess in hypoglycaemia or pancreatitis episodes.
Basile C et al. · European journal of preventive cardiology (2026)
Random effects meta-analyses generated mean differences (MDs) or risk ratios (RRs) along with 95% confidence intervals (CIs).
GLP1-RAs reduced SBP by 3.4 mmHg (95% CI 2.8-4.0) and DBP by 0.9 mmHg (95% CI 0.5-1.2).
All-cause mortality was reduced by 18% (RR 0.82, 95% CI 0.76-0.90).
GLP-1RAs also significantly improved glycemic control for patients with T2D, with tirzepatide performing the best for glycemic control.
Zhang S, Yu B, Xu J, Jin S, Li Y, Bing H, Li J, Ma X, Zhang X, Zhao L. · Diabetes technology & therapeutics (2025)
In terms of Δ body weight, retatrutide (12 mg qw) was the most effective treatment (mean difference = -26.56% [95% confidence interval: -43.89% to -3.01%]).
Tirzepatide (15 mg qw) demonstrated good weight loss ability in all three ΔBW models, ΔBW-NDOOG (-22.76% [-26.45% to -18.50%]), ΔBW-T2DCG (-11.09% [-12.39% to -9.44%])), and ΔBW-T2DAG (-4.97% [-5.84% to -4.12%]).
GLP-1RAs also significantly improved glycemic control for patients with T2D, with tirzepatide performing the best for glycemic control.
Funding The study was funded by Eli Lilly and Company.
Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, Harris C. · The lancet. Diabetes & endocrinology (2025)
This substudy assessed percent change from baseline to week 36 in total body fat mass versus placebo and dulaglutide.
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA 1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m 2 .
The prespecified primary substudy endpoint was percent change from baseline to week 36 in total fat mass, as measured by dual-energy X-ray absorptiometry (DXA).
However, this difference is likely minimal, given the numerous studies excluded from the meta-analysis where both treatment arms had zero events.
Wen J, Nadora D, Bernstein E, How-Volkman C, Truong A, Joy B, Kou M, Muttalib Z, Alam A, Frezza E. · Endocrinology, diabetes & metabolism (2025)
Meta-analysis showed a significantly increased risk of pancreatitis (RR: 1.44, 95% CI 1.09-1.89, p = 0.009), but not when stratified by background medications (RR: 1.28, 95% CI 0.87-1.87) and without background medications (RR: 1.37, 95% CI 0.91-2.05).
Pancreatic cancer and GLP-1 RA use showed no significant association (RR: 1.30, 95% CI 0.86-1.97).
However, a significant increase was found with background medications (RR: 1.85, 95% CI 1.05-3.26, p = 0.03), but not without (RR: 0.81, 95% CI 0.43-1.55).
the mean change from baseline in HbA1c concentration was -1·69%... with retatrutide 4 mg, -1·86%... with 9 mg, and -1·94%... with 12 mg, versus -0·81%... with placebo... The mean percentage change from baseline in bodyweight was -11·5%... with retatrutide 4 mg, -13·9%... with 9 mg, and -15·3%... with 12 mg, versus -2·6%... with placebo.
Bajaj HS, Welch M, Shah P, Luna E, Jaouimaa FZ, Liu B, Liu R, Chen Y, Patel H, Bartee A. · Lancet (2026)
First published phase-3 retatrutide trial (TRANSCEND-T2D-1, n=537): once-weekly subcutaneous retatrutide 4/9/12 mg vs placebo as monotherapy over 40 weeks in type 2 diabetes inadequately controlled by diet and exercise
HbA1c fell -1.94% at 12 mg vs -0.81% placebo (placebo-adjusted up to -1.12%; all p<0.0001); bodyweight fell -15.3% at 12 mg vs -2.6% placebo
GI events were the most frequent adverse events (mild-to-moderate, subsiding over time); AE discontinuation 2-5% vs 0% placebo; no severe hypoglycemia
This review provides an updated synthesis of therapeutic developments and outlines priorities for future research, regulatory policy, and equitable global integration as incretin-based therapies have evolved into a versatile class addressing glycaemic control, weight loss, and cardio-metabolic risk.
Gupta M et al. · The Indian journal of medical research (2026)
Dual GIP/GLP-1 agonist tirzepatide and triple agonist retatrutide have shown unprecedented efficacy, with up to 24% body weight reduction and improvement in hepatic and inflammatory markers.
Despite promising outcomes, challenges persist in terms of cost, accessibility, and the underrepresentation of low- and middle-income countries in major trials.
Pharmacogenomic variability may also influence therapeutic response.
Pharmacovigilance quantitative and qualitative data strengthens evidence for dysesthesias associated with GLP-1R agonists already observed in clinical trials of semaglutide, tirzepatide, and retatrutide.
Laroche ML et al. · European journal of clinical pharmacology (2026)
Pharmacovigilance quantitative and qualitative data strengthens evidence for dysesthesias associated with GLP-1R agonists already observed in clinical trials of semaglutide, tirzepatide, and retatrutide.
Published in European journal of clinical pharmacology (2026)
This perspective underscores the urgent need for scientific engagement, equity considerations, and policy preparedness, positioning retatrutide as a watershed in obesity treatment and a blueprint for future poly-agonist therapies.
Ganamurali N, Sabarathinam S. · Clinical pharmacology in drug development (2026)
Retatrutide (LY3437943), a novel triple agonist targeting GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors, represents a transformative advance in obesity pharmacotherapy.
Phase 2 trials report unprecedented weight reductions, comparable to bariatric surgery, with additional benefits for metabolic comorbidities such as NASH and cardiovascular disease.
Retatrutide exemplifies rational multi-agonist peptide engineering and signals a paradigm shift in systems pharmacology.
Summary Retatrutide, a triple agonist now in phase 3 trials, has the potential to become the most effective pharmacological treatment for obesity while also offering substantial benefits in T2D management and other cardiometabolic risk factors.
Goldney J, Hamza M, Surti F, Davies MJ, Papamargaritis D. · Current cardiovascular risk reports (2025)
Retatrutide achieved up to 24.2% mean weight loss after 48 weeks in individuals with obesity and 16.9% in those with T2D after 36 weeks.
In the T2D study, HbA1c improved by 2.2%, with 82% of participants reaching HbA1c ≤ 6.5%.
Retatrutide also improved multiple cardiometabolic parameters, including blood pressure, lipids, waist circumference, and liver fat (82% reduction in hepatic steatosis).
Its potential for kidney protection is promising, though clinicians should be mindful of managing gastrointestinal tolerability.
Pallavi K, Chandra A, Kumar K, Martand K, Sahu SS, Mohan L, Verma A. · Maedica (2025)
A significant mean reduction in HbA1c of -1.04% (95% CI -1.42 to -0.67) and a noticeable loss in weight, reaching up to -24.2%, were both linked with retatrutide treatment.
A subgroup analysis indicated that the glycemic benefits were dose-dependent, with lower doses (≤8 mg) demonstrating a greater HbA1c reduction (-1.39%) than higher doses (≥12 mg, -0.65%).
Furthermore, secondary analyses pointed toward possible renoprotective effects, evidenced by a reduction in albuminuria.
14Systematische Übersichtn=29,506 · very large study2025
Personalized treatment selection based on patient characteristics is recommended.
Sinha B, Ghosal S. · Obesity (Silver Spring, Md.) (2025)
Outcomes included mean weight loss, achievement of ≥ 5%, ≥ 10%, and ≥ 15% weight loss, waist circumference (WC), BMI, and adverse events (AEs) at ≥ 36 weeks.
Results Retatrutide and dual agonists achieved equivalent mean weight loss (-11.0 kg), surpassing GLP-1RAs (-9.0 kg), with retatrutide excelling at achieving ≥ 15% weight loss (OR 54.6).
Meta-regression showed type 2 diabetes mellitus (T2DM) reduced weight loss by 4.338 kg for GLP-1RAs and 5.016 kg for dual agonists, with enhanced outcomes in female-dominant or high-BMI cohorts.
Our results suggest that enhanced modification of eating behaviours with retatrutide may assist with weight reduction in adults with type 2 diabetes.
Kanu C, Boye KS, Poon JL, Goetz I, Williamson S, Lou J, Hartman ML, Martin CK, Coskun T. · Diabetes, obesity & metabolism (2025)
Results Compared with placebo, participants who received retatrutide ≥4 mg reported greater reductions from baseline in overall appetite, hunger, and prospective food consumption (l at Week 24 (all p <0.05)).
Dietary Restraint increased from baseline versus placebo only in participants who received retatrutide 12 mg at Week 36 (all p <0.05).
WHAT WERE THE MAIN RESULTS?: This study showed that adults with type 2 diabetes who received higher doses of retatrutide reported being less likely to feel hungry or overeat compared to those who received no treatment (i.e., placebo) or those who received dulaglutide.
16Beobachtungsstudien=15,584 · very large study2024
Dual or triple receptor agonists (GLP-1 plus glucose-dependent insulinotropic polypeptide and/or Glucagon receptor) are more effective for weight loss than GLP-1 receptor agonists.
Xie Z, Zheng G, Liang Z, Li M, Deng W, Cao W. · Metabolism: clinical and experimental (2024)
The primary outcome was the percentage change in body weight from baseline.
In addition, disparities in race, BMI, and treatment cycles did not significantly increase the incidence of adverse events.
Finally, the sensitivity and publication bias analyses indicated that the basic analysis results were reliable.
At 48 weeks, the least-squares mean percentage change in the retatrutide groups was -8.7% in the 1-mg group, -17.1% in the combined 4-mg group, -22.8% in the combined 8-mg group, and -24.2% in the 12-mg group, as compared with -2.1% in the placebo group.
Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. · N Engl J Med (2023)
Phase-2, double-blind, randomized, placebo-controlled trial in 338 adults with obesity (or overweight + a weight-related condition), once-weekly subcutaneous retatrutide 1-12 mg vs placebo for 48 weeks
Mean weight loss at 48 weeks reached -24.2% at 12 mg vs -2.1% placebo — the largest reported for an incretin-class drug
At 48 weeks, ≥15% weight loss occurred in 83% of the 12 mg group; GI adverse events were dose-related and mostly mild-to-moderate, partially mitigated by a lower starting dose
In people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists.
Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T. · Lancet (2023)
Phase-2, double-blind, double-dummy, placebo- and active-comparator (1.5 mg dulaglutide)-controlled trial in 281 adults with type 2 diabetes, once-weekly retatrutide 0.5-12 mg over 36 weeks
HbA1c fell up to -2.02% at 24 weeks (12 mg) vs -0.01% placebo and -1.41% dulaglutide; reductions exceeded dulaglutide at the higher doses
Bodyweight fell dose-dependently up to -16.94% at 36 weeks vs -2.02% with dulaglutide
Conclusions Together, these results suggest that the GCGR agonism of retatrutide could lead to reduced circulating ANGPTL3/8 concentrations, which may then contribute to decreases in TG and LDL-C levels.
Wen Y, Lemen D, Lin Y, Chen YQ, Regmi A, Roell WC, Thomas MK, Hartman ML, Coskun T, Milicevic Z, Haupt A, Ruotolo G, Konrad RJ. · Diabetes, obesity & metabolism (2025)
Materials and methods In post-hoc analyses of two phase 2 retatrutide trials, concentrations of ANGPTL3/8, ANGPTL4/8 complex (ANGPTL4/8), ANGPTL3 and ANGPTL4 were measured using dedicated immunoassays to determine percent changes from baseline.
Results ANGPTL3/8 reductions were observed with 8 and 12 mg retatrutide doses in participants with type 2 diabetes, and with 1, 4, 8 and 12 mg retatrutide doses in participants with obesity or overweight but without diabetes.
In both cases, ANGPTL3/8 decreases paralleled retatrutide-induced reductions in TG and LDL-C.
The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo).
Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML. · Nat Med (2024)
Phase-2a, randomized, double-blind, placebo-controlled MASLD substudy (n=98) of the obesity trial, in participants with ≥10% liver fat, once-weekly retatrutide 1-12 mg vs placebo
Liver fat fell ~81-82% at 8/12 mg by 24 weeks vs +0.3% placebo
Normal liver fat (<5%) was reached by 79% (8 mg) and 86% (12 mg) of participants vs 0% placebo