Effects of tirzepatide on weight management in patients with and without diabetes: a systematic review and meta-analysis

Sep 27, 2025International journal of obesity (2005)

Tirzepatide's effects on weight control in people with and without diabetes

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Abstract

Tirzepatide led to a 9.06 kg weight reduction in patients with diabetes and an 18.11 kg reduction in those without diabetes compared to placebo.

Tirzepatide produced significantly greater weight loss in both patients with diabetes and those without, with relative reductions of -9.54% and -17.15%, respectively.
The probability of achieving weight reductions of ≥5%, ≥10%, and ≥15% was significantly higher with tirzepatide in both subpopulations.
Improvements were observed in BMI, waist circumference, blood pressure, hemoglobin A1c, and lipid levels with tirzepatide treatment.
Weight-related benefits were greater in patients without diabetes compared to those with diabetes.
The safety profile of tirzepatide was similar across both groups, primarily involving mild to moderate adverse events.

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AIMS: To conduct a systematic review and meta-analysis comparing tirzepatide versus placebo for weight management, with analyses stratified by diabetes status to precisely assess its efficacy and safety in individuals with and without diabetes.

METHODS: We systematically searched MEDLINE, Embase, and Cochrane Library for randomized controlled trials comparing once-weekly tirzepatide (5-15 mg) versus placebo in adults with or without diabetes for at least 26 weeks. For each subpopulation analysis, the random-effects model was used to calculate pooled risk ratios (RRs) and mean differences (MDs), with their 95% confidence intervals, for dichotomous and continuous endpoints, respectively. Statistical significance was considered at p < 0.05.

RESULTS: We included five trials (n = 2,174) in patients with diabetes (BMI ≥ 23 kg/m) and five (n = 4,467) in patients without diabetes (BMI ≥ 27 [≥24 in Asia] kg/m). Compared with placebo, tirzepatide led to significantly greater relative and absolute weight reductions in patients with (RR -9.54%, p < 0.01; MD -9.06 kg, p < 0.01) and without diabetes (RR -17.15%, p < 0.01; MD -18.11 kg, p < 0.01). In both subpopulations, tirzepatide also significantly increased the probability of achieving weight reductions of ≥5%, ≥10%, and ≥15%, as well as improved BMI, waist circumference, blood pressure, hemoglobin A1c, and lipid levels. Notably, weight-related benefits with tirzepatide were significantly greater in patients without diabetes, whereas its safety was similar across subpopulations and predominantly consisted of mild to moderate, well-tolerated adverse events. 2 2

CONCLUSIONS: Compared with placebo, tirzepatide resulted in statistically significant and clinically meaningful weight reduction, especially in patients without diabetes (with overweight/obesity), with an acceptable safety profile.

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Effects of tirzepatide on weight management in patients with and without diabetes: a systematic review and meta-analysis

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