Analysis of five weight-loss drugs finds phentermine-topiramate and liraglutide most effective
The findings give adults weighing prescription weight-loss medication a one-year picture of likely benefit and tolerability, but leave long-term safety unanswered.
A network meta-analysis published in JAMA in 2016 found that all five FDA-approved prescription weight-loss medications it examined helped overweight and obese adults lose more weight than placebo over one year, and that phentermine-topiramate and liraglutide were the most effective of the five [1].
The analysis combined 28 clinical trials, each comparing one of the medications with an inactive placebo. Together the trials included more than 29,000 patients, all followed for at least a year [1]. The drugs studied were orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate and liraglutide [1].
All five outperformed placebo. After a year, 23% of people taking placebo had lost at least 5% of their body weight, compared with 44% to 75% of those taking a weight-loss medication. On average, participants on medication lost 3 to 19 pounds more than those on placebo [1].
The gap between drugs was wide. People taking phentermine-topiramate were about nine times more likely to lose at least 5% of their body weight than people taking placebo, and those taking liraglutide were nearly six times more likely [1]. The analysis identified those two as the most effective of the group [1].
Tolerability did not track with effectiveness. Participants taking liraglutide and naltrexone-bupropion were the most likely to stop their medication because of side effects or other adverse events [1].
Why it matters for patients
The results give a one-year sense of what a prescription weight-loss drug may realistically do. The share of people who lost at least 5% of body weight ranged from 44% to 75% depending on the drug, compared with 23% on placebo, and the average extra loss ranged from 3 to 19 pounds [1]. The chance of a meaningful result therefore varied widely by medication, and roughly a quarter to more than half of participants did not reach the 5% mark on the drug they took [1].
Effectiveness and tolerability were separate questions. Liraglutide was among the most effective drugs in the analysis and also among those most often stopped for side effects, as was naltrexone-bupropion [1]. The analysis did not measure effects on heart disease, diabetes, quality of life or death, so it does not answer whether losing weight with these drugs changed those outcomes. Costs and insurance coverage are not addressed.
Semaglutide and tirzepatide are not among the five medications studied [1].
What the analysis could not answer
The reported results cover only the first year of treatment. The authors said more research is needed to assess the long-term impact of weight-loss medication, including long-term safety and effectiveness [1].
The design also limits comparisons between drugs. Each trial compared a medication with placebo rather than with another medication, so no trial in the analysis put one of these drugs directly up against another [1].
How these five drugs compare with newer options, and how they perform beyond a year, has not been reported in this analysis [1].
Sources
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