Retatrutide Results in the Clinical Trials

Before the numbers

Retatrutide results from clinical trials have drawn attention across the medical community because the weight-loss figures are the largest reported for any drug in Phase 2 trials of comparable length. In a 48-week Phase 2 obesity study, participants at the highest tested amount lost an average of 24.2% of their body weight, compared to 2.1% with placebo ^[1]. That is roughly three to four times the weight loss of previous single-target weight-loss medicines.

This page collects the published efficacy numbers from every completed retatrutide trial — Phase 1b, Phase 2 obesity, Phase 2 type 2 diabetes, Phase 2 MASLD (liver fat), and the first Phase 3 results. Every number has a citation. Numbers are study averages, not individual outcomes — variation between people in trials is wide, and real-world results in non-trial settings cannot be predicted from trial data.

Phase 1b results: weight and glucose

Trial: Urva S et al., Lancet 2022 (n=72 adults with T2D, 12 weeks) ^[4]

• Placebo-adjusted weight change at highest dose cohort: −8.96 kg (90% CI: −11.16 to −6.75)
• Daily glucose reduction at 3 mg: −2.8 mmol/L
• Half-life established: approximately 6 days
• Treatment-emergent adverse events: 63% of participants, predominantly gastrointestinal
• Safety profile: characterized as acceptable for Phase 2 development

These early results from 12 weeks signaled efficacy that was substantially larger than Phase 1b data from predecessor compounds in the same receptor class.

Phase 2 obesity trial results

Trial: Jastreboff AM et al., N Engl J Med 2023 (n=338 adults with obesity, 48 weeks) ^[1]

Primary endpoint — mean body-weight change at 48 weeks:

• 1 mg: −8.7%
• 4 mg: −17.3%
• 8 mg: −22.8%
• 12 mg: −24.2%
• Placebo: −2.1%

Secondary endpoints:

• BMI reduction at 12 mg: proportional to weight change
• Waist circumference reduction: significant and dose-graded
• No plateau in the weight-loss curve at 48 weeks (loss still ongoing at trial end at 12 mg)

Safety:

• GI adverse events (nausea, diarrhea, vomiting, constipation): dose-related; nausea up to 45% at 12 mg
• Discontinuation due to adverse events: 18% at 12 mg
• Dose-dependent heart-rate increase: peaking around 24 weeks
• No severe hypoglycemia

A pooled systematic review (Misra et al. 2025, n=691 from 3 RCTs) confirmed the 12 mg dose as maximally effective across weight, BMI, and waist circumference endpoints ^[7].

Phase 2 type 2 diabetes results

Trial: Rosenstock J et al., Lancet 2023 (n=281 adults with T2D, 36 weeks) ^[2]

Primary endpoint — HbA1c change at 24 weeks (12 mg vs placebo):

• 12 mg: −2.02%
• Placebo: −0.01%

Body weight at 36 weeks (12 mg vs placebo):

• 12 mg: −16.94%
• Placebo: −3.00%

Safety:

• Mild-to-moderate GI adverse events: 35% of participants
• No severe hypoglycemia
• No deaths

The simultaneous HbA1c and weight reduction in a T2D population — with no severe hypoglycemia — established the safety profile needed for Phase 3 development in this indication.

Phase 2 MASLD liver-fat results

Trial: Sanyal AJ et al., Nature Medicine 2024 (n=98 adults with obesity/overweight and MASLD, 48 weeks) ^[5]

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

• 1 mg: −42.9%
• 4 mg: −57.0%
• 8 mg: −81.4%
• 12 mg: −82.4%
• Placebo: +0.3%

Liver fat normalization (reaching <5% liver fat):

• 12 mg: 86% of participants at 24 weeks

Sustained reductions at 48 weeks:

• 12 mg: −86.0% (further improvement from 24-week mark)

These are the largest pharmacologically produced liver-fat reductions reported in any published randomized trial. MASLD (metabolic dysfunction-associated steatotic liver disease — formerly non-alcoholic fatty liver disease) is a common comorbidity of obesity with no previously approved pharmacological treatment with effects of this magnitude.

Phase 3 results: TRANSCEND-T2D-1

Trial: Bajaj HS et al., Lancet 2026 (n=537 adults with T2D on diet/exercise only, 40 weeks) ^[12]

Primary endpoint — HbA1c change at 40 weeks (12 mg vs placebo):

• 12 mg: −1.94%
• Placebo: −0.81%

Body weight change:

• 12 mg: −15.3%
• Placebo: −2.6%

Safety:

• Adverse events predominantly mild-to-moderate GI
• No severe hypoglycemia
• Discontinuation due to adverse events: 9.8% retatrutide vs 2.2% placebo

This is the first Phase 3 retatrutide trial to publish results. The TRIUMPH-1, -2, and -3 trials (obesity, obesity+T2D, obesity+CVD) are ongoing ^[9][10][11].

Cardiovascular risk factor findings

A 2024 conference abstract presented at the ACC (Kommu S et al., J Am Coll Cardiol 2024) reported retatrutide-associated improvements in lipid and cardiovascular risk factors alongside weight loss ^[8]. Full numeric results were not yet published in peer-reviewed form as of mid-2026. Dedicated cardiovascular outcomes trials are registered and ongoing; their results will be required before the full cardiovascular risk-benefit profile is known.

For summary comparison across the incretin polyagonist class: a 2026 meta-analysis (Chan ZH et al.) found the class as a whole significantly reduced body weight, waist circumference, HbA1c, and fasting glucose versus placebo ^[13].