New Study Compares 19 Weight-Loss Injections and Their Health Impacts
A comprehensive meta-analysis reviewed 262 studies involving nearly 100,000 participants to compare 19 existing and experimental weight-loss drugs. The research assessed medications including tirzepatide (marketed as Mounjaro in Israel), semaglutide (Wegovy), orforglipron (to be named Foundio in Israel), and various combinations. After one year, tirzepatide led with an average body weight reduction of 14.9%, followed closely by the experimental drug cagrilintide at 14.8%, semaglutide tablets at 10.9%, orforglipron at 9.9%, and injectable semaglutide at 9.8%.
Beyond weight loss, these drugs improve blood sugar control, reduce insulin resistance, and may lower blood pressure, blood lipids, and liver fat. Some studies also found reduced risks of heart attacks, strokes, heart failure, and kidney disease progression in certain groups. However, side effects such as nausea, vomiting, diarrhea, constipation, and loss of lean body mass, including muscle, were common. The loss of lean mass is particularly concerning for elderly patients, those with low protein intake, and individuals not engaging in strength training. Researchers emphasize monitoring muscle strength, nutrition, and physical function rather than focusing solely on weight numbers.
Notably, injectable semaglutide was the only drug significantly linked to reduced all-cause mortality (19%), heart attacks (28%), and heart failure (57%). Tirzepatide was associated with a 51% reduction in heart failure risk. However, cardiovascular event data were limited and influenced by participant health profiles, including preexisting heart disease or diabetes. The review found no convincing evidence of kidney failure reduction or significant quality-of-life improvements across most drugs, though measurement limitations and short study durations may have affected these findings.
Gastrointestinal side effects increased with more effective weight loss drugs and were a common reason for treatment discontinuation. Gradual dose escalation may reduce symptoms but does not eliminate them for all patients. Researchers caution against ranking these drugs as a simple league table, noting that the best choice depends on individual factors such as diabetes status, heart and kidney health, gastrointestinal conditions, other medications, cost, availability, and patient preference. Most studies lasted only months to a year, leaving long-term effects on weight maintenance, muscle mass, fractures, mental health, and decades-long use unknown.
