Endpoint by endpoint
Retatrutide Results Across the Phase 1b, Phase 2 and Phase 3 Trials
The efficacy readouts a clinician looks for, each set against the trial that produced it — with the cross-trial caveats named.
The short version
This page collects retatrutide results across the trials in one place — the numbers a clinician would look for, study by study. Retatrutide is an investigational triple-agonist, and its trial results have been unusually large for a drug still in development. The headline retatrutide results: up to a 24.2% mean drop in body weight over 48 weeks at the top Phase 2 dose [1], a 2.02-point HbA1c reduction in type 2 diabetes [2], and an 82.4% cut in liver fat in a fatty-liver substudy [5]. Below, each readout is set against its trial — Phase 1b, the two Phase 2 programs, the fatty-liver substudy, a pooled meta-analysis, and the ongoing Phase 3 TRIUMPH set — with the caveat that these come from separate trials and are not a substitute for a direct head-to-head comparison. None of it is a treatment recommendation.
Phase 1b: first-in-human pharmacokinetics and signal
The first-in-human Phase 1b trial (72 adults with type 2 diabetes, HbA1c 7.0–10.5%) tested ascending weekly doses over 12 weeks. It established the roughly six-day half-life that underpins weekly dosing, and the highest-dose group lost 8.96 kg more than placebo (90% CI -11.16 to -6.75) over the 12 weeks [4]. Daily glucose fell by 2.8 mmol/L at 3 mg. Treatment-emergent adverse events occurred in 63% of participants, mostly gastrointestinal, with an overall safety profile the investigators judged acceptable [4].
For a first-in-human study, that is a strong early signal: a phase designed mainly to characterize safety and pharmacokinetics also produced a clear, dose-related weight and glucose effect. It set the two design choices that carried through the rest of the program — once-weekly subcutaneous dosing anchored on the six-day half-life, and stepwise escalation to manage the gastrointestinal events [4].
Phase 2: the obesity and diabetes readouts
The 48-week Phase 2 obesity trial (338 adults) is the marquee readout: a mean body-weight change of -24.2% at 12 mg once weekly versus -2.1% with placebo [1]. Gastrointestinal adverse events were dose-related and mostly mild-to-moderate, and a dose-dependent heart-rate increase peaked around 24 weeks [1].
The 36-week Phase 2 diabetes trial (281 adults) paired glycemic and weight endpoints: HbA1c fell by 2.02 percentage points at 24 weeks (versus -0.01 with placebo) and body weight by 16.94% at 36 weeks (versus -3.00%), both at 12 mg [2]. Mild-to-moderate gastrointestinal events affected about 35% of participants; there was no severe hypoglycemia and no deaths [2]. A Phase 2-program analysis reported dose-dependent weight loss accompanied by improvements in glycemia, lipids, and blood pressure across the dose range [12].
Phase 2a: the fatty-liver substudy
A 48-week Phase 2a substudy focused on the liver (98 participants with obesity or overweight and MASLD, at least 10% liver fat by MRI-PDFF, without type 2 diabetes). Relative liver-fat reductions at 24 weeks were 42.9%, 57.0%, 81.4%, and 82.4% at the 1, 4, 8, and 12 mg doses versus a 0.3% increase on placebo, and 86% of participants at 12 mg reached a normal (<5%) liver-fat level [5]. The reductions were sustained to 48 weeks, reaching -86.0% at 12 mg [5]. Related Phase 2 analyses have also examined weight-linked comorbidities — obstructive sleep apnea severity and knee-osteoarthritis pain — endpoints carried into the Phase 3 program [14].
Pooled evidence: what the meta-analysis found
Pooling the randomized evidence, a 2025 systematic review and meta-analysis of three trials (878 patients) found a mean weight difference of -14.33% versus placebo, with no significant difference in overall adverse events (RR 1.11, P=0.24) [13]. A 2025 review synthesizing the triple-agonist pharmacology and the Phase 1/2 data characterized the up-to ~24% weight loss as a step-change over prior incretin therapies [6]. A meta-analysis is useful precisely because it pools multiple randomized trials and reports a combined estimate with a measure of consistency; the -14.33% figure is lower than the single-trial 12 mg headline because it averages across doses and populations rather than isolating the top arm [13]. The absence of a significant difference in overall adverse events in that pooled analysis is a reassuring early signal, but the review authors are careful to frame it against short follow-up and Phase 2 sample sizes [13]. Cross-trial pooling is informative but is not the same as a controlled head-to-head; that distinction is the whole point of the comparison on retatrutide vs tirzepatide.
Phase 3: the TRIUMPH program, still open
The Phase 3 TRIUMPH program is ongoing and has not reported primary results as of mid-2026. It spans obesity (TRIUMPH-1, NCT05929066 [20]), obesity with type 2 diabetes (NCT05931367 [21]), a dedicated study in obesity and cardiovascular disease (NCT05882045 [16]), and a cardiovascular-outcomes and kidney-function trial (NCT06383390 [17]); a dedicated kidney trial, TRANSCEND-CKD, is examining renal endpoints [23]. Until those pivotal trials read out, the durability of the weight effect, the cardiovascular and renal outcomes, and any head-to-head standing remain formally open [7]. The Phase 2 numbers above are the current ceiling of the evidence, not a verdict.