Retatrutide Results in the Clinical Trials

The short version

Retatrutide results across Phase 1 and Phase 2 trials are unusually strong for an investigational compound. The headline number from Phase 2 obesity: -24.2% mean body-weight change at 12 mg over 48 weeks in 338 adults, versus -2.1% for placebo. No approved drug in this class has produced that magnitude in a Phase 2 trial.

The results come with tradeoffs: nausea affected nearly half of participants at the highest dose, and 18% discontinued. Heart rate increased measurably with dose. Long-term safety data do not yet exist — Phase 3 is collecting them.

This page summarizes all the Phase 1b and Phase 2 efficacy and safety outcome data in one place, with original citations for each number. For what research-use community members report outside trials, see Retatrutide effects.

Phase 1b results: first-in-human data

Trial: 72 adults with type 2 diabetes, multiple-ascending-dose, subcutaneous once weekly, 12 weeks ^[4].

Key efficacy outcomes:

• Placebo-adjusted weight loss at highest dose group: -8.96 kg (90% CI -11.16 to -6.75 kg)
• Fasting daily glucose at 3 mg: -2.8 mmol/L versus placebo

Key PK outcomes:

• Half-life: ~6 days
• Route: subcutaneous, once weekly — the only route establishing adequate PK for the dose schedule

Safety: TEAEs in 63%, predominantly GI; acceptable at all doses. No severe hypoglycemia.

This trial established that the dosing schedule (once weekly, slow escalation) was pharmacokinetically justified and tolerability-manageable — the foundation on which Phase 2 was designed.

Phase 2 obesity results

Trial: 338 adults with obesity (BMI ≥30, or ≥27 with comorbidity; 51.8% male), randomized to 1/4/8/12 mg once weekly or placebo, 48 weeks (NCT04881760) ^[1].

Primary efficacy: mean percent body-weight change at 48 weeks

Safety signals:

• Nausea: ~23% (1 mg) to ~45% (12 mg)
• Vomiting: 12–28% across doses
• Diarrhea: 12–20%
• Constipation: 12–22%
• Discontinuation due to AEs: 3% (1 mg) to 18% (12 mg)
• Injection-site reactions: ~8%
• Heart-rate increase: dose-dependent, peaking ~24 weeks; mean ~5–7 bpm at highest doses
• Severe hypoglycemia: none reported
• Deaths: none

Phase 2 type 2 diabetes results

Trial: 281 adults with type 2 diabetes (HbA1c 7.0–10.5%), randomized to 0.5–12 mg once weekly with dose escalation versus placebo or active comparator, 36 weeks (NCT04867785) ^[2].

Efficacy at 12 mg vs placebo:

• HbA1c (glycated hemoglobin — 3-month average blood glucose marker) at 24 weeks: -2.02% vs -0.01%
• Body weight at 36 weeks: -16.94% vs -3.00%

Safety: Mild-moderate GI AEs in ~35% of participants. No severe hypoglycemia events. No deaths. Background insulin participants required dose reductions during the trial — the GLP-1/GIP insulin-augmenting effect created hypoglycemia risk in combination with exogenous insulin ^[2].

MASLD substudy results

Trial: 98 participants with obesity or overweight and MASLD (metabolic dysfunction-associated steatotic liver disease — the current term for fatty liver tied to metabolic risk factors; formerly NAFLD), ≥10% liver fat by MRI-PDFF (magnetic resonance imaging proton density fat fraction — a non-invasive measure of liver fat), no T2D. Part of the 48-week obesity trial (NCT04881760) ^[5].

Relative liver-fat change at 24 weeks (MRI-PDFF):

Normal liver fat (<5%) achieved in 86% of 12 mg participants at 24 weeks. Reductions sustained at 48 weeks (-86.0% at 12 mg).

Phase 3 TRIUMPH program: what is being measured

Phase 3 trials are ongoing as of mid-2026. No Phase 3 efficacy data have been published. Trial numbers and primary endpoints from ClinicalTrials.gov:

• NCT05929066 (TRIUMPH-1): Obesity, primary endpoint body-weight reduction
• NCT05931367 (TRIUMPH-2): Obesity with type 2 diabetes
• NCT06383390: Cardiovascular outcomes + active-comparator trial vs tirzepatide
• NCT05882045 (TRANSCEND-CKD): Kidney outcomes in chronic kidney disease

Reviews note Phase 3 weight-loss targets that may approach bariatric-surgery magnitude ^[8]. A 2025 pipeline review in an expert opinion journal characterizes the Phase 3 program as defining the ceiling of pharmacological weight loss ^[7].

For the kidney and cardiometabolic context of the GLP-1 receptor class, a 2025 JCI review is the authoritative current reference ^[11]. For a broad mechanistic synthesis of the triple-agonist class, the 2026 multi-agonist review covers the NUSH (nutrient-stimulated hormone) framework within which retatrutide sits ^[13]. For Retatrutide research details including cryo-EM mechanism data, see the research page.