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

To further determine the placebo response and the associated factors in trials of anti-obesity medications (AOMs). 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. 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. 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. This study looked at how often a “placebo” (a pill or injection with no medicine) causes weight loss in clinical trials for obesity treatments. Researchers analyzed 182 past studies. They found that people taking a placebo still lost some weight—about 1.13 kg on average. Interestingly, “fake” injections led to more weight loss than “fake” pills. People without diabetes lost more weight than those with type 2 diabetes, while people with type 1 diabetes tended to gain weight. Younger people, those with a higher starting weight, and more women also lost more weight on placebo. These results show that simply taking placebo in a treatment trial can influence weight. Therefore, future obesity studies should carefully account for the placebo response to ensure new drugs are truly effective. Guo and Yang et al. examine placebo response and associated factors in placebo-controlled trials of anti-obesity medications. Their meta-analysis indicated a significant placebo response, which was associated with age, sex, baseline BMI, and baseline body weight in patients with overweight or obesity with or without diabetes.