Source: Jastreboff AM et al., The New England Journal of Medicine , 2022, 10.1056/NEJMoa2206038
Purpose of the study
To evaluate the effect of Tirzepatide – a dual agonist of GIP and GLP-1 receptors – on body weight reduction and metabolic indicators in overweight and obese people without diabetes.
Tirzepatide is an injectable peptide that activates receptors of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), potentially combining the effects of both hormones for greater effectiveness in weight control.
Study design
Type: phase 3, double-blind, randomized, placebo-controlled
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Participants: 2539 adults with BMI ≥30 or ≥27 with at least one associated complication
Duration: 72 weeks (incl. 20-week titration period)
Interventions: Tirzepatide 5 mg, 10 mg, 15 mg, 1× weekly, subcutaneously
Control: placebo + lifestyle changes (diet and activity)
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End points:
Percentage change in weight from baseline
≥5% weight reduction
Secondary: ≥10%, ≥15%, ≥20% reduction; waist circumference, HbA1c, blood pressure
Main results
Weight reduction
Average 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)
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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% returned to normoglycemia (vs 61.9% placebo)
Body composition
Total fat mass reduction: −33.9% (tirzepatide) vs −8.2% (placebo)
A more favorable fat/muscle ratio
Safety
Most common side effects: nausea, diarrhea, constipation
Mainly mild to moderate, transient, occurring upon titration
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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.
It is well tolerated; gastrointestinal effects are transient.
It shows potential to approximate the effect of bariatric surgery in a controlled environment.
Restrictions
Short-term (72 weeks); long-term safety data lacking
Mostly female and Caucasian (limited representation)
No diabetic patients
Practical importance
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Tirzepatide is a new class of peptide agonist (GIP/GLP-1) showing over 20% weight reduction.
It represents a promising tool for controlling obesity and its associated risks.
Suitable for future clinical studies in metabolic and cardiovascular medicine.
