What is retatrutide used for?

What it is being studied for

• Obesity (phase 2): average weight loss of 24.2% at 12 mg vs 2.1% on placebo after 48 weeks, in 338 adults; a human randomized trial [1].
• Obesity (phase 3, TRIUMPH-1): weight change of −17.6%, −23.7% and −25.0% at 4, 9 and 12 mg vs −3.9% on placebo over 80 weeks, in 2,339 adults without diabetes; a published human randomized trial [2].
• Knee osteoarthritis pain and sleep apnoea (TRIUMPH-1 sub-groups): WOMAC pain score fell by 3.2–3.6 points vs 1.9 on placebo (n=574), and breathing interruptions during sleep fell by 22.9–34.3 vs 9.9 events per hour (n=243); human randomized trial [2].
• Obesity with type 2 diabetes (phase 3, TRIUMPH-2): weight change of −11.9%, −16.8% and −18.8% vs −5.1% on placebo over 80 weeks, in 1,152 adults; a published human randomized trial [3].
• Type 2 diabetes, blood-sugar control (phase 2): HbA1c, a three-month blood-sugar measure, fell by 0.43% at 0.5 mg and by about 2% at higher doses at 24 weeks, in 281 people; human randomized trial [4].
• Type 2 diabetes (phase 3, TRANSCEND-T2D-1): HbA1c fell 1.69–1.94% vs 0.81% on placebo and weight 11.5–15.3% vs 2.6% over 40 weeks, in 537 people on retatrutide alone; a published human randomized trial [5].
• Liver fat (MASLD): relative liver-fat change of −82.4% at 12 mg vs +0.3% on placebo at 24 weeks, with normal liver fat reached by 86% vs 0%, in 98 participants from the phase 2 obesity trial; human randomized trial substudy [6].
• Heart and kidney outcomes: a phase 3 trial is registered, with no results published as of October 2026 [7].

How it works

1. It is a single peptide that switches on three hormone receptors at once: GIP, GLP-1 and glucagon [1][8].
2. In laboratory tests its activity at the glucagon and GLP-1 receptors was balanced, with stronger activity at the GIP receptor [8].
3. In obese mice, the GIP and GLP-1 arms reduced how much the animals ate, and the glucagon arm added extra energy use on top, which increased weight loss [8].
4. Its half-life is about 6 days in people with type 2 diabetes, which is what allows once-weekly injections [9].
5. What sets it apart from GLP-1-only and GIP/GLP-1 medicines is the third, glucagon-receptor arm, which in mice raised energy expenditure rather than only lowering food intake [8].

Adverse events reported

• Gastrointestinal effects were the most common, dose-related and mostly mild to moderate in phase 2; a lower starting dose (2 mg vs 4 mg) partly reduced them [1].
• Heart rate rose with dose in phase 2, peaking at 24 weeks and declining after [1].
• Gastrointestinal effects were the most common adverse events in TRIUMPH-1 [2].
• Diarrhoea was reported in 27%, 34% and 34% of the 4, 9 and 12 mg groups in TRIUMPH-2 [3].
• In TRANSCEND-T2D-1, 2–5% on retatrutide vs 0% on placebo stopped because of adverse events; no severe low blood sugar was reported, and two deaths in the 4 mg group were reported as unrelated to the study drug [5].
• In a 12-week phase 1b study, 63% on retatrutide vs 54% on placebo had treatment-emergent adverse events, mostly gastrointestinal [9].

Forms

Every published human trial gave retatrutide as a once-weekly injection under the skin [1][3]. No oral or nasal form was found in PubMed or ClinicalTrials.gov. A pre-approval expanded-access programme is listed on ClinicalTrials.gov [10].

How injected, oral and nasal peptides compare, and which forms have human data: Peptide pills vs nasal sprays vs injections.