BETTER LIVING THROUGH
CHEMISTRY
Pioneering the future of peptide science
Research and Clinical Trials
Research & Clinical Trials: Retatrutide
Retatrutide (LY-3437943) is a triple-receptor agonist peptide designed to target GLP-1, GIP, and glucagon receptors — three key hormonal pathways that influence appetite, metabolism, and blood sugar regulation. It is currently being studied for its powerful effects on weight loss, insulin sensitivity, liver fat reduction, and cardiometabolic health.
Phase 1 – First-in-Human & Dose-Escalation
- Half-life of ~6 days — long enough for once-weekly dosing
- Dose-dependent drug levels in blood (higher doses yielded predictable increases)
- Common side effects were mild to moderate and mostly gastrointestinal (e.g., nausea)
- No serious adverse events were observed at therapeutic doses
These results gave researchers the confidence to proceed to Phase 2 trials, using weekly subcutaneous injections for further evaluation.
Reference: PubMed – Phase 1 Study
Phase 2 – Proving Effectiveness in Humans
A. Type 2 Diabetes Trial (n ≈ 190)
- Significant reduction in HbA1c (a key marker of long-term blood sugar)
- Fasting glucose and body weight decreased across all dosing levels
- Well-tolerated overall, with gastrointestinal symptoms being the most common issue
This trial demonstrated that Retatrutide works similarly to — and in some cases better than — other incretin-based therapies already approved for diabetes treatment.
B. Obesity Trial (n = 338)
In a separate Phase 2 trial, adults with obesity (with or without other conditions) received weekly injections of Retatrutide for 48 weeks. This study focused purely on weight loss and overall metabolic improvement.
6‑Month (24‑Week) Results
- 1 mg: –7.2%
- 4 mg (start 2 mg): –11.8%
- 4 mg (start 4 mg): –13.9%
- 8 mg (start 2 mg): –16.7%
- 8 mg (start 4 mg): –17.9%
- 12 mg (start 2 mg): –17.5%
- Placebo: –1.6%
48‑Week (11‑Month) Final Outcomes
| Dose | 24-Week Loss | 48-Week Loss |
|---|---|---|
| 1 mg | –7.2% | –8.7% |
| 4 mg (start 2 mg) | –11.8% | –16.3% |
| 4 mg (start 4 mg) | –13.9% | –17.8% |
| 8 mg (start 2 mg) | –16.7% | –21.7% |
| 8 mg (start 4 mg) | –17.9% | –23.9% |
| 12 mg (start 2 mg) | –17.5% | –24.2% |
| Placebo | –1.6% | –2.1% |
Reference: NEJM – Phase 2 Obesity Trial
C. NAFLD Substudy (n = 98)
This substudy focused on non-alcoholic fatty liver disease (NAFLD), which commonly coexists with obesity and type 2 diabetes.
- Liver fat was reduced by:
- 81.4% (8 mg group)
- 82.4% (12 mg group)
- >85% of patients reached normalized liver fat (<5%)
- Significant improvements in:
- Triglycerides
- Waist circumference
- Insulin resistance
- Leptin/adiponectin balance
- Fat metabolism (e.g., elevated ketone levels)
Reference: Nature Medicine – Liver Fat Analysis
Phase 3 – Pivotal Trials in Progress
Retatrutide is currently in Phase 3 trials — the final step before FDA submission. These global studies are designed to confirm long-term safety, effectiveness, and comparison against leading drugs.
| Trial (NCT ID) | Population | Focus |
|---|---|---|
| NCT06859268 | Obesity | 80-week open-label + 36-week randomized withdrawal study |
| NCT05929066 | Post-weight-loss maintenance | Assess sustained results after initial success |
| NCT06662383 | Obesity | Compare directly with tirzepatide (a leading dual agonist) |
| NCT05931367 | Obesity with Osteoarthritis | Test for joint function + weight outcomes |
| NCT05929079 | Type 2 Diabetes with Obesity | Dual focus on blood sugar and body composition |
Summary
- Phase 1: Safe, well-tolerated, suitable for weekly injection
- Phase 2: Demonstrated rapid and substantial weight loss, metabolic improvement, and liver fat reduction
- Phase 3: Evaluating long-term outcomes, comparisons to competitors, and multi-condition populations
If Phase 3 data confirm earlier results, Retatrutide may become the most effective non-surgical treatment yet for obesity and metabolic syndrome.