Popular medications for obesity, including Wegovy and Mounjaro, can produce substantial weight loss, but their effects on quality of life and long-term health may be less impressive than many had hoped. That is the conclusion of a large systematic review published in The BMJ.

Researchers analyzed data from 262 randomized clinical trials involving nearly 100,000 participants. The review compared 19 approved and investigational anti-obesity medications with lifestyle interventions, placebo, or other drug therapies.

The researchers evaluated not only weight loss but also the drugs' effects on quality of life, cardiovascular outcomes, loss of lean body mass, adverse events, and the durability of benefits after treatment discontinuation.

The greatest average weight loss after one year was observed with:

  • Tirzepatide — approximately 14.9% of body weight

  • CagriSema — approximately 14.8%

  • Oral semaglutide — approximately 10.9%

  • Orforglipron — approximately 9.9%

  • Injectable semaglutide — approximately 9.8%

  • Phentermine-topiramate — approximately 8.1%

However, the analysis identified an important pattern: the greater the weight loss, the more frequently adverse effects occurred. The most common side effects included gastrointestinal disorders, fatigue, and loss of lean body mass, including skeletal muscle.

The researchers also highlighted what happens after treatment is discontinued. In many cases, improvements in body weight and overall health were not maintained without ongoing therapy, suggesting that continued treatment may be necessary to sustain the benefits.

Cardiovascular protection was more limited than expected. Only a few medications demonstrated convincing clinical benefits.

Injectable semaglutide was associated with an approximately 19% reduction in all-cause mortality, a 28% lower risk of heart attack, and a 57% reduction in the risk of heart failure. Tirzepatide was also linked to an approximately 51% lower risk of heart failure.

However, none of the medications showed convincing evidence of reducing the risk of kidney failure or producing significant improvements in patients' overall quality of life.

The review also found that tirzepatide produced the greatest reduction in body fat—about 25.7%—but was also associated with the largest loss of muscle mass, averaging 8.3%.

The researchers conclude that obesity treatment should be individualized. When selecting a medication, healthcare providers and patients should consider not only the expected weight loss but also potential risks, treatment costs, drug availability, and the patient's personal preferences.