Retatrutide (GLP-3 Triple Agonist)

Peptide

Retatrutide (also known as GLP-3 or LY3437943) is an investigational triple hormone receptor agonist (GIP/GLP-1/glucagon) by Eli Lilly for obesity, T2DM, and MASLD. Phase 2: 24.2% weight loss at 48 weeks (NEJM 2023). Phase 3 TRIUMPH-4: 28.7% weight loss at 68 weeks. T2DM Phase 2: HbA1c reduction of 2.2%, 82% achieved HbA1c ≤6.5%. MASLD: 86% liver fat reduction at 48 weeks, 93% achieved <5% liver fat. SAFETY: GI side effects common - nausea (43%), diarrhea (33%), vomiting (21%). Dysesthesia reported in ~20% at higher doses. Seven Phase 3 readouts expected 2026.

Quick Answer

What it is

Key findings

Grade A: Body Weight Reduction (Obesity)
Grade A: Glycemic Control (HbA1c) (Type 2 Diabetes)
Grade A: Liver Fat Reduction (Fatty Liver Disease)

Safety

SAFETY CONCERN: Unusual side effect - unpleasant skin sensations in ~20% at 12mg dose.

⚠️ Research Notice

This peptide information is for educational and research purposes only. Peptides may not be FDA-approved for human use and may only be legally available for research purposes. Consult qualified healthcare professionals before considering any peptide compounds.

ℹ️ Quick Facts: Retatrutide (GLP-3 Triple Agonist)

Quick Facts: Retatrutide (GLP-3 Triple Agonist)

Best Evidence:Grade A
Conditions Studied:4
Research Outcomes:14
Grade A Findings:5
Grade B Findings:5
Key Effect:Obesity

4 conditions · 14 outcomes

Detailed Outcomes

Body Weight Reduction

Phase 2 (n=338): 24.2% mean weight loss at 48 weeks with 12mg. 100% achieved ≥5%, 93% achieved ≥10%, 83% achieved ≥15% weight loss. Phase 3 TRIUMPH-4: 28.7% weight loss at 68 weeks. Most effective weight loss drug in clinical trials to date.

large↓Improves

Gastrointestinal Side Effects

SAFETY CONCERN: Phase 3 TRIUMPH-4: Nausea 38-43%, diarrhea 33-35%, constipation 22-25%, vomiting 20-21%, decreased appetite 18-19%. Generally mild-moderate and manageable with dose titration. Higher dropout rates than placebo.

moderate↑Worsens

Dysesthesia

SAFETY CONCERN: Unusual side effect - unpleasant skin sensations in ~20% at 12mg dose. Described as mild for most patients, rarely causing discontinuation. Mechanism unclear - may relate to glucagon receptor activation.

small↓Worsens

Glycemic Control (HbA1c)

Phase 2 T2DM (n=281): HbA1c reduction of 2.0-2.2% at 36 weeks. 82% achieved HbA1c ≤6.5%. Superior to 1.5mg dulaglutide comparator. Fasting glucose significantly improved across all doses.

large↓Improves

Liver Fat Reduction

Phase 2a MASLD (n=98): 82-86% relative reduction in liver fat at 48 weeks with 8-12mg. 89-93% achieved normal liver fat (<5%). Driven by glucagon receptor activation promoting hepatic lipid oxidation.

large↓Improves

Osteoarthritis Pain

Phase 3 TRIUMPH-4: WOMAC pain score reduced by 4.5 points (75.8%) at 68 weeks. 12% of patients on 12mg achieved complete pain freedom vs 4.2% placebo. Likely secondary to weight loss reducing joint stress.

large↓Improves

Blood Glucose Control

19 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

moderate↓Improves

Safety/Tolerability

11 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

moderate↑Improves

Kidney Function

6 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

small↑Improves

Liver Protection

6 systematic reviews and preclinical studies support this finding. Evidence includes systematic reviews/meta-analyses. Primarily preclinical evidence.

small↑Improves

GI Protection

2 preclinical studies support this finding. Primarily preclinical evidence.

small↑Improves

Muscle Mass/Function

2 preclinical studies support this finding. Primarily preclinical evidence.

small↑Improves

Anti-Cancer Activity

2 systematic reviews and preclinical studies support this finding. Evidence includes systematic reviews/meta-analyses. Primarily preclinical evidence.

small↑Improves