Placebo response on the weight change and its influencing factors in overweight or obesity with or without diabetes: a meta-analysis of 182 anti-obesity medications trials.

BACKGROUND

To further determine the placebo response and the associated factors in trials of anti-obesity medications (AOMs).

METHODS

PubMed, EMBASE, the Cochrane Center Register of Controlled Trials, and Clinicaltrial.gov website were searched from the inception to December 2025 for placebo-controlled trials of AOMs conducted in patients with overweight or obesity with or without diabetes.

RESULTS

Overall, 182 trials were included. Placebo treatment in AOMs trials generally resulted in a weight loss of 1.13 kg (95% CI, -1.29 to -0.97 kg, P < 0.01). Participants receiving injectable placebo experienced a greater weight reduction than those receiving oral placebo (ES = -1.46 kg, 95% CI, -1.74 to -1.19 kg, P < 0.01 vs. ES = -0.82 kg, 95% CI, -1.05 to -0.59 kg, P < 0.01; P for subgroup comparison <0.001). Patients without diabetes showed a greater weight loss of placebo response than those with type 2 diabetes (ES = -1.92 kg, 95% CI, -2.22 to -1.62 kg, P < 0.01 vs. ES = -0.72 kg, 95% CI, -0.92 to -0.52 kg, P < 0.01; P for subgroup comparison <0.001), whereas individuals with type 1 diabetes had a significant weight gain (ES = 0.76 kg, 95% CI, 0.46 to 1.05 kg, P < 0.01). Meta-regression analyses showed younger age, lower male percentage, higher baseline body mass index and higher baseline body weight were significantly associated with greater weight reduction in placebo response.

CONCLUSION

Our meta-analysis indicated a significant placebo response in trials of AOMs, which was associated with age, sex, baseline BMI and baseline body weight in patients with overweight or obesity with or without diabetes.