How Retatrutide Efficacy is Measured
Retatrutide efficacy is measured primarily by percentage change in body weight from baseline, with secondary endpoints including achievement of categorical weight loss thresholds (≥5%, ≥10%, ≥15%), changes in metabolic parameters (HbA1c, fasting glucose, blood pressure, lipids), and waist circumference reduction. 1, 2
Primary Efficacy Endpoint
- Percentage change in body weight is the primary outcome measure, assessed at 24 weeks in phase 2 trials, with continued measurement through 48 weeks 1
- Weight loss is dose-dependent, ranging from -7.2% at 1 mg to -24.2% at 12 mg after 48 weeks of treatment 1, 2
Secondary Weight-Related Endpoints
Categorical Weight Loss Achievement
- ≥5% weight loss threshold: Achieved by 92-100% of patients on retatrutide 4-12 mg versus 27% on placebo at 48 weeks 1
- ≥10% weight loss threshold: Achieved by 75-93% of patients on retatrutide 4-12 mg versus 9% on placebo at 48 weeks 1
- ≥15% weight loss threshold: Achieved by 60-83% of patients on retatrutide 4-12 mg versus 2% on placebo at 48 weeks 1
Body Composition Measures
- Body mass index (BMI) reduction: Mean difference of -5.38 kg/m² compared to placebo 2
- Waist circumference reduction: Mean difference of -10.51 cm compared to placebo 2
Glycemic Control Parameters (Type 2 Diabetes Patients)
- HbA1c reduction: Mean improvement of -0.91% to -2.2% depending on dose and duration 3, 2
- Fasting plasma glucose: Mean reduction of -23.51 mg/dL compared to placebo 2
- Achievement of glycemic targets: 82% of participants with type 2 diabetes reached HbA1c ≤6.5% after 36 weeks 3
Cardiometabolic Risk Factors
Blood Pressure
- Systolic blood pressure: Mean reduction of -9.88 mm Hg compared to placebo 2
- Diastolic blood pressure: Mean reduction of -3.88 mm Hg compared to placebo 2
Hepatic Outcomes
- Hepatic steatosis reduction: 82% reduction in liver fat content 3
Lipid Parameters
- Improvements in lipid profiles are measured, though specific quantitative data varies by trial 3
Safety and Tolerability Measures
- Adverse event rates: No significant difference in overall adverse events between retatrutide and placebo groups (relative risk: 1.11, P = 0.24) 2
- Gastrointestinal adverse events: Most common side effects, dose-related and mostly mild-to-moderate in severity 1, 4
- Heart rate changes: Dose-dependent increases peaking at 24 weeks, then declining thereafter, with increases up to 6.7 beats/min 1, 4
Assessment Timeline
- Primary endpoint assessment: 24 weeks from baseline 1
- Extended efficacy assessment: 48 weeks for obesity trials, 36 weeks for type 2 diabetes trials 1, 3
- Ongoing monitoring: Phase 3 trials are evaluating long-term cardiovascular and renal outcomes 3