International journal of obesity (2005) · 2026
Indirect comparative efficacy and safety of tirzepatide vs semaglutide for the treatment of obesity or overweight in patients without type 2 diabetes.
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Ciudin Andreea, Johansson Erin, Zimner-Rapuch Sarah, Dimitriadis Georgios K, Bertrand Marine, Curteis Tristan, Clark Laura J, Fan Ludi, Sapin Helene, Bergmann Jean-Francois
Аннотация
BACKGROUND/OBJECTIVES: Tirzepatide is a once-weekly, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) for obesity treatment. This indirect treatment comparison (ITC) assessed the relative efficacy and safety of tirzepatide versus the GLP-1 RA semaglutide.
SUBJECTS/METHODS: Adjusted (for sex, and sex and ethnicity) and unadjusted ITCs compared tirzepatide 5, 10, and 15 mg/week and semaglutide 2.4 mg/week via placebo, all adjunct to reduced-calorie diet and increased physical activity, at primary trial endpoints (Week 68, STEP 1; Week 72, SURMOUNT-1) for adults with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with ≥1 obesity-related complication (ORC), without type 2 diabetes (T2D).
RESULTS: For efficacy estimand unadjusted ITCs, tirzepatide 10 and 15 mg demonstrated statistically significant improvements versus semaglutide in weight reduction (-5.10 kg [-6.63, - 3.57], -6.50 kg [-8.03,-4.97]), participants achieving ≥10/15/20% weight reduction, BMI (-1.87 kg/m2 [-2.43,-1.31], -2.37 kg/m2 [-2.93,-1.81]), waist circumference (-5.25 cm [-6.69,-3.81], -5.75 cm [-7.19,-4.31]), HbA1c(-0.08% [-0.13,-0.03], -0.10% [-0.15, -0.05]) and fasting plasma glucose (-1.69 mg/dL [-3.36,-0.02], -2.52 mg/dL [-4.19,-0.85]). Tirzepatide 5 mg showed non-significant trends of greater improvements in these outcomes versus semaglutide. All tirzepatide doses showed statistically significantly greater decreases in diastolic blood pressure (-1.90 mmHg [-3.19,-0.61], -2.40 mmHg [-3.69,-1.11], -1.30 mmHg [-2.59,-0.01]) and increases in HDL (3.80% [1.23,6.37], 5.40% [2.83,7.97], 5.00% [2.43,7.57]). In participants reporting on body composition, tirzepatide 15 mg demonstrated statistically significant improvements in body composition versus semaglutide, with a reduction of percentage body fat mass (-3.50% [-6.66, -0.34]) and an increase of percentage body lean mass (3.40% [0.40, 6.40]). Results were broadly consistent across adjusted and unadjusted comparisons. Safety profiles of tirzepatide and semaglutide were generally similar.
CONCLUSIONS: In this ITC for obesity treatment in adults without T2D, with obesity, or overweight with ≥1 ORC, compared with semaglutide, tirzepatide 10 or 15 mg was associated with improvements in weight reduction, body composition and several cardiometabolic risk factors and generally similar safety profiles.
SUBJECTS/METHODS: Adjusted (for sex, and sex and ethnicity) and unadjusted ITCs compared tirzepatide 5, 10, and 15 mg/week and semaglutide 2.4 mg/week via placebo, all adjunct to reduced-calorie diet and increased physical activity, at primary trial endpoints (Week 68, STEP 1; Week 72, SURMOUNT-1) for adults with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with ≥1 obesity-related complication (ORC), without type 2 diabetes (T2D).
RESULTS: For efficacy estimand unadjusted ITCs, tirzepatide 10 and 15 mg demonstrated statistically significant improvements versus semaglutide in weight reduction (-5.10 kg [-6.63, - 3.57], -6.50 kg [-8.03,-4.97]), participants achieving ≥10/15/20% weight reduction, BMI (-1.87 kg/m2 [-2.43,-1.31], -2.37 kg/m2 [-2.93,-1.81]), waist circumference (-5.25 cm [-6.69,-3.81], -5.75 cm [-7.19,-4.31]), HbA1c(-0.08% [-0.13,-0.03], -0.10% [-0.15, -0.05]) and fasting plasma glucose (-1.69 mg/dL [-3.36,-0.02], -2.52 mg/dL [-4.19,-0.85]). Tirzepatide 5 mg showed non-significant trends of greater improvements in these outcomes versus semaglutide. All tirzepatide doses showed statistically significantly greater decreases in diastolic blood pressure (-1.90 mmHg [-3.19,-0.61], -2.40 mmHg [-3.69,-1.11], -1.30 mmHg [-2.59,-0.01]) and increases in HDL (3.80% [1.23,6.37], 5.40% [2.83,7.97], 5.00% [2.43,7.57]). In participants reporting on body composition, tirzepatide 15 mg demonstrated statistically significant improvements in body composition versus semaglutide, with a reduction of percentage body fat mass (-3.50% [-6.66, -0.34]) and an increase of percentage body lean mass (3.40% [0.40, 6.40]). Results were broadly consistent across adjusted and unadjusted comparisons. Safety profiles of tirzepatide and semaglutide were generally similar.
CONCLUSIONS: In this ITC for obesity treatment in adults without T2D, with obesity, or overweight with ≥1 ORC, compared with semaglutide, tirzepatide 10 or 15 mg was associated with improvements in weight reduction, body composition and several cardiometabolic risk factors and generally similar safety profiles.