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Investigational

Retatrutide

Eli Lilly · Code: LY3437943

A triple GIP, GLP-1, and glucagon receptor agonist. The first Phase 3 result (TRIUMPH-4, 2026) showed 28.7% average weight loss at 68 weeks.

Investigational — not approved or available to prescribe.

Main trial result

28.7%

TRIUMPH-4 (Phase 3) · 12 mg, 68 weeks, adults with knee osteoarthritis

Stage

Phase 3

Timeline (not confirmed)

2027 (estimated — not confirmed)

Form

Weekly injection

What it is

A triple GIP, GLP-1, and glucagon receptor agonist. The first Phase 3 result (TRIUMPH-4, 2026) showed 28.7% average weight loss at 68 weeks. The addition of glucagon receptor agonism on top of GIP and GLP-1 may further boost metabolic rate and fat burning beyond what dual agonists achieve.

Why this matters:

Compared to currently approved treatments, this drug is being studied because it may produce significantly greater weight loss than any currently approved medication. These treatments are still under investigation, and results in larger trials may differ from early data.

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Medical disclaimer: This website is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any treatment. Prices shown are United States self-pay or list prices and vary by insurance and country.

Development stage and timeline

Current stage:

Phase 3: TRIUMPH programme complete. TRIUMPH-4 results published 2026. TRIUMPH-1, TRIUMPH-2, TRIUMPH-3 data expected 2026.

Next milestone:

FDA decision expected 2027. Not yet approved.

How it works

Activates three receptors simultaneously: GIP (enhances fat storage signalling), GLP-1 (reduces appetite, slows gastric emptying), and glucagon (increases metabolic rate and fat burning). The triple mechanism may produce synergistic weight loss beyond what dual agonists achieve.

Timeline note: Phase 3 TRIUMPH-4 data shows progressive weight loss throughout 68 weeks; weight had not plateaued by end of study — suggesting ongoing loss possible with longer treatment

Phase 2 trial data by dose

In the Phase 2 trial, people were randomly assigned to different doses or to a dummy pill. Here is how much weight each dose group lost. Phase 3 data is pending.

DoseAt 24 weeksAt 48 weeks
1 mg–7.2%–8.7%
4 mg–12.9%–17.1%
8 mg–17.3%–22.8%
12 mg–17.5%–24.2%
Placebo–1.6%–2.1%

Phase 3 trial results

In the following Phase 3 trials, participants were randomly assigned to Retatrutide or a dummy pill.

TRIUMPH-4
Adults with obesity and knee osteoarthritis (average baseline weight 112.7 kg / 248.5 lbs; BMI 40.4) · 68 weeks

In the TRIUMPH-4 trial, participants lost an average of 28.7% of their body weight at the 12 mg dose (about 71.2 lbs / 32.3 kg on average) — alongside a 75.8% reduction in knee pain. At the 9 mg dose, average weight loss was 26.4%. Placebo: 2.1% weight loss.

Phase 3 programme

  • TRIUMPH-4 (published 2026): Adults with obesity and knee osteoarthritis — 28.7% weight loss at 68 weeks
  • TRIUMPH-1: Adults with obesity, no type 2 diabetes — data expected 2026
  • TRIUMPH-2: Adults with obesity and type 2 diabetes — data expected 2026
  • TRIUMPH-3: Adults with Class II/III obesity and established cardiovascular disease — data expected 2026

Side effects (early-stage data)

Frequencies from Phase 2 trial data. Final Phase 3 safety profile may differ.

Nausea(45%)
Diarrhoea(28%)
Vomiting(22%)
Constipation(14%)
Decreased appetite(30%)

Notable findings

  • ✓28.7% average weight loss at 68 weeks (TRIUMPH-4 Phase 3)
  • ✓75.8% reduction in knee osteoarthritis pain alongside weight loss (TRIUMPH-4)
  • ✓Cardiometabolic improvements across blood pressure, lipids, and blood sugar (Phase 2 + Phase 3)
  • ✓100% of participants at 8 mg and 12 mg achieved ≥5% weight loss in Phase 2

What this tends to offer vs. what it involves

What this tends to offer

  • ✓28.7% average weight loss
  • ✓Triple mechanism addresses appetite and metabolism
  • ✓75.8% reduction in knee pain in TRIUMPH-4
  • ✓Once-weekly injection format

What this involves

  • Still under investigation — not yet FDA approved
  • Nausea expected similar to or higher than GLP-1 drugs (45% in Phase 2)
  • Price and insurance coverage unknown pending approval
  • Approval timeline estimates not confirmed

Sources & references

  1. [1]
    Phase 2 randomised controlled trial (NEJM 2023)
    338 adults with obesity, no type 2 diabetes · 48 weeks
    At 12 mg dose: 24.2% mean weight loss at 48 weeks — weight had not plateaued. 100% achieved ≥5% loss; 93% ≥10%; 83% ≥15%. GI side effects consistent with incretin class. Discontinuation: 6–16% across doses.
    New England Journal of Medicine (2023) ↗
  2. [2]
    TRIUMPH-4 Phase 3 trial (published 2026)
    Adults with obesity and knee osteoarthritis (average BMI 40.4, baseline weight ~112.7 kg) · 68 weeks
    28.7% mean weight loss at 12 mg dose (about 71.2 lbs average). 26.4% at 9 mg. Knee pain (WOMAC) reduced by 75.8% vs 40.3% placebo. Cardiometabolic improvements including reduced blood pressure and cholesterol. First successful Phase 3 trial.
    Eli Lilly press release / investor.lilly.com (2026) ↗

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