Retatrutide Results in the Clinical Trials

Before the numbers

Retatrutide results from the Phase 2 trials have attracted significant scientific attention because the weight-loss figures — up to a mean of 24.2% body-weight reduction over 48 weeks — are larger than those documented for any prior approved therapy in this class ^[1]. This page collects those results, organized by trial and outcome measure.

These are findings from controlled, randomized clinical trials conducted in defined patient populations under medical supervision. They describe what the trials measured in those populations — not what any individual will experience. Retatrutide is investigational; it is not an approved drug, and these results do not authorize its use outside a supervised clinical trial. Every number on this page cites the published study from which it is drawn.

Phase 2 obesity trial — primary endpoints (Jastreboff 2023, NEJM [1])

Trial design: 48-week randomized, double-blind, placebo-controlled Phase 2 trial. 338 adults with obesity (BMI ≥30) or overweight (BMI 27-<30) with at least one weight-related comorbidity; 51.8% male. Doses: 1, 4, 8, or 12 mg subcutaneous once weekly.

Body-weight change (48 weeks):

• 12 mg: mean -24.2% (vs -2.1% placebo)
• 8 mg: mean -22.8%
• 4 mg: mean -17.3%
• 1 mg: mean -8.7%

Proportion achieving ≥5% weight loss at 48 weeks:

• 12 mg: 100%
• Placebo: 26%

GI adverse events: Dose-related nausea, diarrhea, vomiting, and constipation; nausea in up to 45% at the highest dose; mostly mild-to-moderate.

Discontinuation: 18% at 12 mg (primarily GI tolerability); 2-5% placebo.

Heart rate: Dose-dependent increase peaking at approximately 24 weeks; mean increase approximately 5-7 bpm at highest doses.

Injection-site reactions: Approximately 8% of participants.

Phase 2 type 2 diabetes trial — primary endpoints (Rosenstock 2023, Lancet [2])

Trial design: 36-week randomized, double-blind, placebo- and active-controlled Phase 2 trial. 281 adults with type 2 diabetes. Doses: 0.5-12 mg subcutaneous once weekly with stepwise escalation.

HbA1c change at 24 weeks:

• 12 mg: -2.02% (vs -0.01% placebo)
• Intermediate doses: -1.37% (3 mg) to -2.20% (4/8/12 mg escalating arm)

Body-weight change at 36 weeks:

• 12 mg: -16.94% (vs -3.00% placebo)
• Intermediate doses: -7.92% (2 mg) to -14.93% (4/8/12 mg escalating arm)

GI adverse events: 35% of participants (mild-to-moderate).

Hypoglycemia: No severe hypoglycemia events; patients on background insulin required insulin dose de-escalation.

Deaths: Zero.

Phase 1b — first-in-human results (Urva 2022, Lancet [4])

Trial design: Phase 1b randomized, double-blind, placebo-controlled multiple-ascending-dose trial. 72 adults with type 2 diabetes (HbA1c 7.0-10.5%). Doses: 0.5, 1.5, 3, 3/6, and 3/6/9/12 mg subcutaneous once weekly, 12 weeks.

Pharmacokinetics: Half-life approximately 6 days, supporting once-weekly dosing.

Placebo-adjusted weight loss: -8.96 kg (90% CI -11.16 to -6.75) at highest escalating dose group over 12 weeks.

Fasting glucose: -2.8 mmol/L at 3 mg.

Safety: Treatment-emergent adverse events in 63% of participants, mostly GI; no deaths; acceptable safety profile.

MASLD substudy (Sanyal 2024, Nature Medicine [5])

Trial design: Phase 2a randomized controlled substudy. 98 participants with obesity/overweight and MASLD (≥10% liver fat by MRI-PDFF) but without type 2 diabetes. Doses: 1, 4, 8, 12 mg once weekly.

Relative liver-fat change (24 weeks):

• 12 mg: -82.4% (vs +0.3% placebo)
• 8 mg: -81.4%
• 4 mg: -57.0%
• 1 mg: -42.9%

Participants reaching normal liver fat (<5%) at 24 weeks: 86% at 12 mg.

Sustained response at 48 weeks: -86.0% at 12 mg.

Recent 2024–2025 data

Body composition (Coskun 2025, Lancet Diabetes Endocrinol ^[12]). DXA substudy in type 2 diabetes participants confirmed dose-dependent total fat mass reductions during retatrutide-induced weight loss. Lean body mass also reduced, proportionally less than fat. Subjects at higher sarcopenic risk warrant monitoring.

Kidney parameters (2025, Kidney Int Rep ^[13]). UACR reduced ~37% (12 mg, T2D) and ~28-31% (8-12 mg, obesity). Creatinine-based eGFR increased 5.3-8.5 mL/min/1.73m² in obesity group. Favorable renal-safety signal.

Lipids and metabolism (Pearson 2026, J Clin Endocrinol Metab ^[14]). Triglycerides and insulin-resistance markers reduced at higher doses. Fatty acid oxidation changes mediated 23.2% of weight-reduction response in non-T2D participants.

ANGPTL3/8 (Wen 2025, Diabetes Obes Metab ^[15]). ANGPTL3/8 reductions at 8-12 mg paralleled TG and LDL-C reductions; GCGR agonism mechanistically implicated.

For retatrutide vs tirzepatide direct comparisons across Phase 2 data and the head-to-head Phase 3 design, see the dedicated page. For Retatrutide effects community reports, see the effects page.