Source: Jastreboff A.M. et al., The New England Journal of Medicine, 2022, 10.1056/NEJMoa2206038
Study Objective
To evaluate the effect of Tirzepatide – a dual GIP and GLP-1 receptor agonist – on body weight reduction and metabolic parameters in people with overweight and obesity without diabetes.
Tirzepatide is an injectable peptide that activates receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), potentially combining the effects of both hormones for greater efficacy in weight management.
Study Design
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, subcutaneously
Control: placebo + lifestyle changes (diet and activity)
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Endpoints:
Percent change in weight from baseline
≥5% weight reduction
Secondary: ≥10%, ≥15%, ≥20% reduction; waist circumference, HbA1c, blood pressure
Key Results
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%
Achievement of ≥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% returned to normoglycemia (vs 61.9% placebo)
Body composition
Overall reduction in fat mass: −33.9% (tirzepatide) vs −8.2% (placebo)
More favorable fat-to-muscle ratio
Safety
Most common adverse reactions: nausea, diarrhea, constipation
Mainly mild to moderate, transient, occurring during titration
Discontinuation due to side effects: 4.3–7.1% (tirzepatide) vs 2.6% (placebo)
Conclusions
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 approximate the effect of bariatric surgery in a controlled setting.
Limitations
Short-term (72 weeks); no data on long-term safety
Predominantly women and white race (limited representativeness)
No diabetic patients
Practical Implications
Tirzepatide is a new class of peptide agonist (GIP/GLP-1), demonstrating over 20% weight reduction.
Represents a promising tool for managing obesity and associated risks.
Suitable for future clinical studies in metabolic and cardiovascular medicine.
