Trial Results
Retatrutide Results in the Clinical Trials
A complete account of what the Phase 1, 2, and 3 trials found — weight loss, blood-sugar control, liver fat reduction, safety signals, and the Phase 3 TRIUMPH readout.
The short version
Retatrutide has produced the largest weight-loss results ever reported for a pharmacotherapy in controlled trials. In a Phase 2 study of 338 adults with obesity, the highest dose — 12 mg once weekly — produced a mean weight loss of 24.2% over 48 weeks, compared with 2.1% for placebo [1]. That number stands as a record. It is also a Phase 2 number, not a Phase 3 confirmation.
Phase 3 is underway. The first Phase 3 result — from the TRANSCEND-T2D-1 trial in type 2 diabetes — reported 15.3% weight loss and 1.94% HbA1c reduction versus placebo at 40 weeks [12]. GI side effects were the dominant adverse event. Retatrutide results are real, large, and still being characterized. Nothing is approved yet.
Phase 1b results: establishing the pharmacokinetic profile
The first published retatrutide results came from the Phase 1b trial (Urva 2022), which enrolled 72 adults with type 2 diabetes and studied escalating weekly subcutaneous doses over 12 weeks [4]. The key finding: a half-life of approximately 6 days supported once-weekly dosing. At the highest dose group, placebo-adjusted weight loss was 8.96 kg (90% CI: -11.16 to -6.75 kg). Daily glucose fell by 2.8 mmol/L at 3 mg. GI adverse events occurred in approximately 63% of participants and were described as the dominant safety finding. The Phase 1b authors recommended advancement to Phase 2.
Phase 2 obesity trial: the -24.2% result in context
The 48-week Phase 2 obesity trial (Jastreboff 2023) is the primary evidence base for retatrutide's weight-loss efficacy [1]. Participants: 338 adults with obesity (BMI ≥30, or 27-<30 with metabolic comorbidity), 51.8% male, on a stable background of lifestyle intervention. Doses: 1, 4, 8, or 12 mg once weekly, with escalation.
Mean body-weight change at 48 weeks:
- Placebo: -2.1%
- 1 mg: -8.7%
- 4 mg: -17.3%
- 8 mg: -22.8%
- 12 mg: -24.2%
The dose-response was clear and consistent. At 12 mg, 83% of participants lost more than 15% of body weight — a clinical response threshold — and 26% lost more than 30%. Discontinuation due to adverse events was 18% at 12 mg, primarily from GI effects.
A 2025 review synthesizing these results characterized the up-to 24% weight loss as "a step-change versus prior incretin therapies" [6]. A 2026 evidence review described triple GLP-1/GIP/glucagon agonists as demonstrating "the highest achievable weight loss with pharmacotherapy" [7].
Phase 2 type 2 diabetes results
The Lancet Phase 2 trial (Rosenstock 2023) enrolled 281 adults with type 2 diabetes and studied escalating once-weekly doses over 36 weeks [2]. At 24 weeks, 12 mg produced HbA1c reduction of 2.02% versus 0.01% in placebo. At 36 weeks, 12 mg produced body-weight reduction of 16.94% versus 3.00% in placebo. No deaths were reported; no severe hypoglycemia in participants not on background insulin. GI adverse events occurred in approximately 35% of participants.
A 2026 network meta-analysis found retatrutide ranked highest among glucagon receptor agonists for both weight and HbA1c reduction versus placebo, with only retatrutide's HbA1c effect reaching significance across the pooled analysis [13].
Phase 2 liver disease substudy results
A Phase 2a trial in 98 participants with obesity or overweight and MASLD (metabolic dysfunction-associated steatotic liver disease — fatty liver disease — with at least 10% liver fat by MRI scan) reported striking reductions in liver fat [5]. At 24 weeks, 12 mg produced a relative liver-fat reduction of 82.4% (measured by MRI proton density fat fraction — a non-invasive scan). Normal liver fat levels (<5%) were reached by 86% of participants in the 12 mg group. Reductions were sustained at 48 weeks: 86.0% liver-fat reduction at 12 mg.
This is a particularly notable finding because MASLD is a highly prevalent and undertreated condition with few approved treatments. Retatrutide's Phase 2 liver data are among the most striking in the MASLD literature, though Phase 3 confirmation is required before any clinical conclusions can be drawn.
Phase 3 results: TRANSCEND-T2D-1
The first Phase 3 retatrutide result, published in the Lancet in 2026 (Bajaj 2026), enrolled 537 adults with type 2 diabetes inadequately controlled by diet and exercise [12]. Over 40 weeks:
- Retatrutide 12 mg: HbA1c -1.94%, body weight -15.3%
- Placebo: HbA1c -0.81%, body weight -2.6%
Adverse events were predominantly mild-to-moderate GI effects. No severe hypoglycemia was reported in this monotherapy population. The results support the Phase 2 efficacy signal in a larger, Phase 3-level trial, though this is one trial in one indication — the broader TRIUMPH program continues.
For a head-to-head research comparison with the dual agonist tirzepatide, see retatrutide vs tirzepatide.