Source: Jastreboff A.M. et al., The New England Journal of Medicine, 2022, 10.1056/NEJMoa2206038
To evaluate the effect of Tirzepatide – a dual GIP and GLP-1 receptor agonist – on body weight reduction and metabolic markers in people with overweight and obesity without diabetes.
Tirzepatide is an injectable peptide that activates the receptors of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), potentially combining the effects of both hormones for greater efficacy in weight control.
Type: phase 3, double-blind, randomized, placebo-controlled
Participants: 2539 adults with BMI ≥30 or ≥27 with at least one related complication
Duration: 72 weeks (incl. 20-week titration period)
Interventions: Tirzepatide 5 mg, 10 mg, 15 mg, once weekly, subcutaneous
Control: placebo + lifestyle changes (diet and activity)
Endpoints:
Percentage change in weight from baseline
≥5% weight reduction
Secondary: ≥10%, ≥15%, ≥20% reduction; waist circumference, HbA1c, blood pressure
Weight Reduction
Mean change after 72 weeks:
5 mg: −15.0% (95% CI, −15.9 to −14.2)
10 mg: −19.5% (95% CI, −20.4 to −18.5)
15 mg: −20.9% (95% CI, −21.8 to −19.9)
Placebo: −3.1%
Achieving ≥5% reduction: 85–91% vs 35% (placebo)
≥20% reduction: up to 57% (15 mg) vs 3% (placebo)
Cardiometabolic Effects
Improvements in waist circumference, blood pressure, lipid profile, and insulin sensitivity.
In prediabetes: 95.3% reverted to normoglycemia (vs 61.9% placebo)
Body Composition
Total fat mass reduction: −33.9% (tirzepatide) vs −8.2% (placebo)
More favorable fat-to-muscle ratio
Safety
Most common adverse reactions: nausea, diarrhea, constipation
Mostly mild to moderate, transient, occurring during titration
Discontinuation due to side effects: 4.3–7.1% (tirzepatide) vs 2.6% (placebo)
Tirzepatide provides significant, sustained weight reduction (up to −21%) over 72 weeks.
Improves cardiometabolic profile and body composition.
Well tolerated; gastrointestinal effects are transient.
Shows potential to approach the effect of bariatric surgery in a controlled setting.
Short-term (72 weeks); lacking long-term safety data
Predominantly women and white race (limited representativeness)
No patients with diabetes
Tirzepatide is a new class of peptide agonist (GIP/GLP-1), showing over 20% weight reduction.
Represents a promising tool for managing obesity and related risks.
Suitable for future clinical studies in metabolic and cardiovascular medicine.