Retatrutide Results: 2026 UK Research Review of Weight Loss, Glycemic and Cardiometabolic Outcomes by Week

Last updated: April 2026 · UK research-grade reference · For laboratory research use only — not for human consumption

Table of Contents

• 1. What retatrutide is and why the results matter
• 2. Weight loss results by week — the 48-week trajectory
• 3. Dose-response curve: 1 mg through 12 mg
• 4. Glycemic results in type 2 diabetes cohorts
• 5. Hepatic results — MASLD and liver fat reduction
• 6. Cardiometabolic shifts: blood pressure, lipids, waist
• 7. How retatrutide results compare to semaglutide and tirzepatide
• 8. Is there a plateau? What week-48 extrapolation suggests
• 9. Safety and tolerability signals alongside the efficacy curve
• 10. What Phase 3 TRIUMPH is likely to show
• 11. UK research procurement and protocol framing
• 12. Frequently asked questions
• 13. References

1. What retatrutide is and why the results matter

Retatrutide (LY3437943) is Eli Lilly’s investigational triple agonist of the GLP-1, GIP and glucagon receptors. It is the first triple-agonist of this class to reach large Phase 2 trials and the first to enter a full Phase 3 programme (TRIUMPH). Unlike semaglutide (single GLP-1 agonist) or tirzepatide (dual GLP-1/GIP agonist), retatrutide adds glucagon receptor activation, which increases resting energy expenditure and mobilises hepatic lipid — two mechanisms that appear to be driving the outsized weight and liver-fat results reported in Phase 2.

For UK research scientists, retatrutide’s Phase 2 dataset is significant for three reasons. First, the magnitude of placebo-adjusted weight loss at week 48 (~24%) exceeds anything previously reported at that timepoint. Second, the trajectory is still steepening at week 48 — most GLP-1 molecules are near-plateaued by that point. Third, the hepatic signal — greater than 80% reduction in liver fat at the 8 mg and 12 mg doses — is unprecedented and positions retatrutide as a candidate for MASLD/MASH research in parallel with obesity work.

2. Weight loss results by week — the 48-week trajectory

The pivotal Phase 2 obesity trial (Jastreboff et al., NEJM 2023, NCT04881760) randomised 338 adults with BMI ≥ 30 (or ≥ 27 with weight-related comorbidity) to placebo or retatrutide at 1, 4, 8 or 12 mg weekly subcutaneous, with dose escalation over the first 12-20 weeks depending on target dose. Results were reported at week 24 and week 48.

Mean percentage weight change from baseline at the 12 mg dose:

• Week 8: approximately −3.5% (during dose escalation)
• Week 16: approximately −7% (most participants now at or near target dose)
• Week 24: −17.5% raw / ~8.7% placebo-adjusted (placebo group was losing weight from lifestyle counselling)
• Week 36: approximately −21% raw
• Week 48: −24.2% raw, placebo-adjusted

Critically, the slope of weight loss was still negative through week 48. In the SURMOUNT-1 tirzepatide trial and STEP-1 semaglutide trial, the curve begins flattening between weeks 36 and 52. Retatrutide at 12 mg had not yet plateaued — the inflection point lies beyond week 48 in the Phase 2 data available.

At the 8 mg dose, week-48 weight loss was approximately −22.8%, and at 4 mg approximately −17.5%, indicating a clear dose-response relationship across the upper range.

3. Dose-response curve: 1 mg through 12 mg

Retatrutide’s dose-response curve in the Phase 2 obesity trial was notably linear — there was no evidence of efficacy ceiling at 12 mg, though tolerability considerations constrained higher doses. Approximate mean week-48 weight loss by dose:

• Placebo: −2.1%
• 1 mg: −8.7%
• 4 mg: −17.1%
• 8 mg: −22.8%
• 12 mg: −24.2%

The proportion of participants achieving ≥ 15% weight loss at week 48:

• 12 mg: 83%
• 8 mg: 77%
• 4 mg: 64%
• Placebo: 2%

The proportion achieving ≥ 25% weight loss at week 48:

• 12 mg: 48%
• 8 mg: 34%
• 4 mg: 10%
• Placebo: 0%

To contextualise, in SURMOUNT-1 at 72 weeks, the proportion of tirzepatide 15 mg participants achieving ≥ 25% weight loss was 36% — a figure retatrutide 12 mg exceeded at just 48 weeks.

4. Glycemic results in type 2 diabetes cohorts

A parallel Phase 2 programme in adults with T2DM (Rosenstock et al., Lancet 2023, NCT04867785) enrolled 281 adults with HbA1c 7.0-10.5% and BMI 25-50 on stable diet, exercise or metformin. At 36 weeks:

• HbA1c reduction at 12 mg: −2.02% from baseline (approximately −1.7% placebo-adjusted)
• Proportion achieving HbA1c < 7.0%: 94% at 12 mg vs 28% on placebo
• Proportion achieving HbA1c < 6.5%: 77% at 12 mg
• Proportion achieving HbA1c < 5.7% (normoglycemia): 27% at 12 mg
• Fasting plasma glucose: reduced by approximately 3.3 mmol/L at 12 mg
• Body weight reduction: −16.9% at 12 mg over the same 36-week window (weight loss in T2DM cohorts is typically smaller than in non-diabetic obesity cohorts across the class)

Hypoglycaemia was rare and confined to participants whose baseline HbA1c was at the low end of the inclusion range — a pattern consistent with GLP-1-class physiology (insulin secretion is glucose-dependent, so severe hypoglycaemia is uncommon except in combination with sulfonylureas or exogenous insulin).

5. Hepatic results — MASLD and liver fat reduction

A 98-participant Phase 2 sub-study in adults with MASLD (Sanyal et al., Nature Medicine 2024) measured liver fat by MRI-proton density fat fraction (MRI-PDFF) at baseline and 24 weeks, with a second assessment at 48 weeks in a subset.

Relative liver fat reduction at week 48 by dose:

• 12 mg: −82.4%
• 8 mg: −81.4%
• 4 mg: −57.0%
• 1 mg: −42.2%
• Placebo: −0.3%

Normalisation of liver fat (defined as MRI-PDFF < 5%) was achieved in:

• 12 mg: 93%
• 8 mg: 93%
• 4 mg: 67%
• Placebo: 0%

This is a remarkable hepatic signal. For comparison, semaglutide 2.4 mg in MASH studies produced liver fat reductions of approximately 30-40% over 72 weeks, and tirzepatide in the SYNERGY-NASH study produced roughly 57% relative reduction at 52 weeks. Retatrutide’s ability to normalise liver fat in > 90% of 8-12 mg participants by week 48 reflects the glucagon-receptor contribution to hepatic lipid mobilisation — a mechanism absent in single and dual agonists.

6. Cardiometabolic shifts: blood pressure, lipids, waist

Beyond weight and glycaemia, the Phase 2 obesity trial reported the following mean changes at week 48 at the 12 mg dose:

• Systolic blood pressure: −10.2 mmHg (from a baseline mean around 129 mmHg)
• Diastolic blood pressure: −4.5 mmHg
• Waist circumference: approximately −18 cm
• Triglycerides: −35% to −40%
• Non-HDL cholesterol: −13% to −18%
• HDL cholesterol: +5% to +8%
• Fasting insulin: approximately −60%
• HOMA-IR (insulin resistance index): approximately −65%

These cardiometabolic shifts, combined with the primary weight and glycemic results, suggest retatrutide produces a coordinated reversal of the metabolic syndrome cluster — a key reason why the TRIUMPH Phase 3 programme spans obesity, T2DM, MASLD, obstructive sleep apnoea and cardiovascular outcomes in parallel rather than sequentially.

7. How retatrutide results compare to semaglutide and tirzepatide

At maximum approved or studied dose, comparing flagship results:

• Semaglutide 2.4 mg (STEP-1, 68 weeks): −14.9% body weight, −12.4% placebo-adjusted
• Tirzepatide 15 mg (SURMOUNT-1, 72 weeks): −22.5% body weight, −17.8% placebo-adjusted
• Retatrutide 12 mg (Phase 2, 48 weeks, still trending down): −24.2% body weight

The cross-trial comparison has two caveats scientists should weight properly. First, retatrutide’s data are at 48 weeks — not 68 or 72 weeks like the comparators. Second, the Phase 2 population is smaller (n = 338) than the Phase 3 trials used for semaglutide and tirzepatide benchmarks. However, given retatrutide’s curve was still descending at 48 weeks, the 68-72 week readout in TRIUMPH is a plausible point of further divergence rather than convergence.

8. Is there a plateau? What week-48 extrapolation suggests

Across the GLP-1 class, weight loss curves typically display three phases: steep early descent (weeks 0-20), linear middle phase (weeks 20-40), and gradual flattening (weeks 40-68). Semaglutide plateaus around week 60. Tirzepatide’s curve begins flattening around week 52 and reaches near-plateau by week 72.

Retatrutide 12 mg in the Phase 2 data showed roughly linear descent from week 20 through week 48 with no visible inflection. Two scenarios are plausible in TRIUMPH’s 68-88 week readouts:

1. Delayed but convergent plateau — the curve flattens between weeks 52 and 72 in a similar pattern to tirzepatide, pushing terminal weight loss to roughly −28% to −30%.
2. Later plateau, higher terminal value — the additional glucagon-driven energy-expenditure effect prevents early plateau and weight loss continues linearly to week 68, yielding terminal values at or above −32%.

The TRIUMPH-1 and TRIUMPH-2 readouts expected in 2026-2027 will resolve this question empirically.

9. Safety and tolerability signals alongside the efficacy curve

The safety profile across Phase 2 studies is consistent with GLP-1-class expectations, with some mechanism-driven distinctions:

• GI adverse events (nausea, vomiting, diarrhoea, constipation) in 30-60% of participants dose-dependent, most concentrated in the dose-escalation phase. Mild to moderate in most cases and decreasing after target dose achieved.
• Transient heart rate elevation: approximately +5 to +7 bpm at 12 mg — slightly higher than with tirzepatide or semaglutide, reflecting glucagon-receptor activation. Returned toward baseline by week 48.
• Hepatic enzymes: transient elevation in a subset, normalising with continued dosing; no signal of drug-induced liver injury.
• Hypoglycaemia: rare outside of insulin/sulfonylurea combinations.
• Discontinuation due to adverse events: 6-16% dose-dependent across the Phase 2 obesity cohort — comparable to tirzepatide and semaglutide at equivalent phases.

The heart-rate signal warrants monitoring in Phase 3 because it is the most mechanistically distinct finding relative to dual and single agonists, though the observed range is modest and precedent-consistent.

10. What Phase 3 TRIUMPH is likely to show

The TRIUMPH programme (NCT05929079 and sister protocols) is a multi-indication Phase 3 effort, with key arms:

• TRIUMPH-1: Retatrutide in obesity (without T2DM) — ~2,000 participants, 80-week primary endpoint
• TRIUMPH-2: Retatrutide in obesity with comorbidities
• TRIUMPH-3: Retatrutide in T2DM
• TRIUMPH-4: Retatrutide for MASH with biopsy endpoints
• TRIUMPH-Outcomes: Cardiovascular outcomes in obesity/comorbidity population

Based on Phase 2 trajectory, reasonable Phase 3 expectations are: terminal weight loss in the −28% to −32% range at 12 mg over 68-80 weeks; HbA1c reductions sustained above −2.0% in T2DM cohorts; MASH histological resolution in 60-75% of 8-12 mg participants; cardiovascular event reduction in high-risk cohorts similar to or exceeding the 20% RRR observed with semaglutide in SELECT.

11. UK research procurement and protocol framing

For UK scientists designing retatrutide protocols — whether in vitro, ex vivo or in licensed animal work — procurement requirements mirror the wider GLP-1-class standard:

• Purity: ≥ 98% HPLC (≥ 99% is the emerging 2026 norm for flagship research-grade suppliers)
• Identity confirmation: MS (mass spectrometry) on every batch
• Endotoxin testing on batches intended for cell or animal work
• Batch-specific Certificate of Analysis with purity, identity, content, water and acetate content
• Lyophilised peptide dispatched cold-chain to UK addresses
• Reconstitution: bacteriostatic water is the standard diluent for research purposes; aliquots stored at −20°C for medium-term stability

Our UK dispatch operates under these conditions. For standards references, see our Research-Grade Peptides Guide and our UK Research Peptide Buying Guide.

12. Frequently asked questions

How much weight loss does retatrutide produce at 24 weeks vs 48 weeks?

Approximately 17.5% at 24 weeks and 24.2% at 48 weeks at the 12 mg dose in the Phase 2 obesity trial — a continuing linear descent through the full observed window.

Is retatrutide more effective than tirzepatide?

In a cross-trial comparison (not a head-to-head), retatrutide at 12 mg over 48 weeks produced weight loss equal to or exceeding tirzepatide 15 mg over 72 weeks. A direct head-to-head has not yet been completed; TRIUMPH results will resolve the comparison with higher confidence.

What is the minimum effective dose for research-meaningful weight loss?

The 4 mg dose produced approximately −17.1% weight loss at 48 weeks in Phase 2. The 1 mg dose produced −8.7%, which exceeds semaglutide’s 1 mg result in STEP trials.

Does retatrutide work for MASLD/MASH?

The Phase 2 hepatic data are strong — greater than 80% relative liver fat reduction at 8-12 mg doses, with 93% of participants achieving liver fat normalisation. The dedicated TRIUMPH-4 MASH arm with histological endpoints is running.

How does retatrutide compare to semaglutide for diabetes?

Retatrutide 12 mg produced HbA1c reductions of approximately −2.02% at 36 weeks in Phase 2, with 94% of participants reaching < 7.0% — exceeding semaglutide’s typical 1.5-1.8% reduction in SUSTAIN trials.

What dose has the best efficacy-to-tolerability ratio in Phase 2?

Based on published data, 8 mg produced roughly 94% of the 12 mg weight loss (−22.8% vs −24.2%) with a modestly lower GI adverse event burden. For research protocol design, 8 mg is the pragmatic middle-of-curve reference point.

When will Phase 3 TRIUMPH results read out?

TRIUMPH-1 and TRIUMPH-2 primary readouts are expected in late 2026 and through 2027, with TRIUMPH-4 MASH and TRIUMPH-Outcomes extending into 2028.

13. References

1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med 2023;389:514-526.
2. Rosenstock J, Frias J, Jastreboff AM, et al. 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. Lancet 2023;402:529-544.
3. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine 2024;30:2037-2048.
4. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205-216. (SURMOUNT-1)
5. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384:989-1002. (STEP-1)
6. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med 2023;389:2221-2232. (SELECT)
7. Loomba R, Hartman ML, Lawitz EJ, et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med 2024;391:299-310. (SYNERGY-NASH)
8. Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2021;384:1113-1124.
9. Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab 2022;34:1234-1247.e9.
10. ClinicalTrials.gov: NCT05929079 (TRIUMPH-1), NCT05929092 (TRIUMPH-2), NCT05929066 (TRIUMPH-3), NCT05882045 (TRIUMPH-4).

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