A new comprehensive study found that while several newer medications aid in significant weight loss, the most effective drugs produced more side effects. None of the evaluated drugs showed meaningful improvements in quality of life after one year.

A new study published in The BMJ evaluated the effectiveness and safety of 19 medications for adults with overweight or obesity. The analysis, which included nearly 100,000 participants across 262 clinical trials, found that the most effective weight-loss drugs often led to more side effects and higher rates of treatment discontinuation. Despite some health benefits, none of the drugs demonstrated meaningful improvements in quality of life scores after one year.

Study Scope and Methodology

Researchers conducted a systematic review and network meta-analysis, comparing 19 weight-loss drugs against lifestyle changes, placebo, or other medications. The study included randomized controlled trials lasting at least 12 weeks, involving adults with overweight or obesity, with or without related health issues. Data were collected from major medical databases through November 2025, and researchers examined 24 outcomes, including body weight loss, side effects, treatment discontinuation rates, and serious health outcomes like heart attacks and death.

Weight Loss and Side Effects

Two medications, tirzepatide and cagrilinitide-semaglutide, produced the greatest reductions in body weight, leading to about 15% weight loss after one year. Other drugs like oral semaglutide, orforglipron, subcutaneous semaglutide, and phentermine-topiramate resulted in 8% to 11% body weight loss. However, greater weight loss was often associated with increased side effects such as nausea, diarrhea, and fatigue, which sometimes caused patients to stop their medication. Orforglipron and naltrexone-bupropion had the highest rates of discontinuation due to adverse events. The study also noted a loss of lean mass, particularly with tirzepatide and subcutaneous semaglutide, averaging 6% to 8%.

Health Outcomes and Quality of Life

Subcutaneous semaglutide was the only drug linked with lower risks of death from any cause and heart attacks. Both subcutaneous semaglutide and tirzepatide reduced the risk of heart failure, with tirzepatide also lowering hospital admissions for heart failure. No drug convincingly reduced the risk of kidney failure. Despite these health benefits and weight loss, none of the drugs showed meaningful improvements in quality of life scores after one year, suggesting that weight loss alone may not translate to better overall well-being in the short term.