Tirzepatide, semaglutide more efficacious than other FDA-approved drugs for weight loss
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Key takeaways:
- Researchers compared randomized controlled trial data for all FDA-approved medications for obesity.
- Tirzepatide 10 mg and 15 mg and semaglutide 2.4 mg outperformed other drugs for weight-loss efficacy.
Tirzepatide and semaglutide confer greater weight loss than other FDA-approved obesity medications with no significantly higher risk for adverse events, according to findings from a network meta-analysis published in Obesity.
“Over the years, we’ve had all these drugs that were approved by FDA,” Priyanka Majety, MD, assistant professor of internal medicine and adult outpatient diabetes director in the division of endocrinology, diabetes and metabolism at Virginia Commonwealth University Health System, told Healio. “Recently, the GLP-1s and tirzepatide have had such huge success, so we wanted to compare all of the FDA-approved medications for obesity and see if we can provide some guidance to physicians and patients to see which one would be the most beneficial.”
Researchers obtained data from 31 randomized controlled trials assessing weight change for adults with overweight or obesity. Medications included in the meta-analysis were tirzepatide (Zepbound, Eli Lilly), semaglutide (Wegovy, Novo Nordisk), liraglutide (Saxenda, Novo Nordisk), phentermine/topiramate (Qsymia, Vivus), naltrexone/bupropion (Contrave, Nalpropion Pharmaceuticals) and orlistat (Xenical, Roche). Surface under the cumulative ranking curve (SUCRA) analysis was used to rank each medication and assign each a score of 0 to 1. A higher number indicated a higher probability of an event occurring.
The meta-analysis included 35,458 adults. Of the trials, 11 assessed liraglutide, six examined semaglutide, five assessed phentermine/topiramate, five analyzed naltrexone/bupropion, two assessed orlistat and two examined tirzepatide.
Weight-loss efficacy
In SUCRA analysis, phentermine 15 mg/topiramate 92 mg had the highest ranking for achieving a 5% or greater weight loss (SUCRA = 0.979) and 10% or greater weight loss (SUCRA = 0.9308). Phentermine 7.5 mg/topiramate 46 mg was second best for a 5% or greater weight reduction (SUCRA = 0.8964) and third best for achieving a 10% or greater weight loss (SUCRA = 0.867), whereas tirzepatide 15 mg ranked third for achieving a 5% or greater weight loss (SUCRA = 0.7386) and second for a 10% or higher weight reduction (SUCRA = 0.867).
When 15% or greater weight loss was assessed, tirzepatide 15 mg ranked first (SUCRA = 0.9451), followed by tirzepatide 10 mg (SUCRA = 0.878) and semaglutide 2.4 mg (SUCRA = 0.7959). The top-performing drugs were the same when weight reduction compared with placebo was assessed, with tirzepatide 15 mg ranking first (SUCRA = 0.9928), tirzepatide 10 mg ranked second (SUCRA = 0.9312) and semaglutide 2.4 mg ranked third (SUCRA = 0.8556). Orlistat 120 mg (SUCRA = 0.1693) and 60 mg (SUCRA = 0.1455) were the lowest-ranked medications for weight-loss efficacy.
Cardiometabolic changes
Tirzepatide 15 mg was best at reducing waist circumference (SUCRA = 0.9941), followed by tirzepatide 10 mg (SUCRA = 0.9279) and semaglutide 2.4 mg (SUCRA = 0.8343). Tirzepatide was best at lowering HbA1c, with the 15 mg dose (SUCRA = 0.848), 10 mg dose (SUCRA = 0.841) and 5 mg dose (SUCRA = 0.6725) ranked in the top three spots. Orlistat 120 mg topped the rankings for lowering LDL cholesterol (SUCRA = 0.8789), whereas tirzepatide 15 mg was best at reducing total cholesterol (SUCRA = 0.7867) and triglycerides (SUCRA = 0.9843). Naltrexone 32 mg/bupropion 360 mg conferred the greatest HDL cholesterol increase (SUCRA = 0.8757). Tirzepatide 15 mg was best for lowering systolic blood pressure (SUCRA = 0.9457).
“[Tirzepatide] topped the charts in improving [most] cardiometabolic parameters,” Majety said. “I think we should prioritize tirzepatide, followed by the GLP-1 receptor agonists whenever possible, especially in patients where they have coexisting cardiometabolic diseases.”
Safety findings
Naltrexone 32 mg/bupropion 360 mg was the only drug conferring a higher risk for any adverse event compared with placebo (RR = 1.45; 95% CI, 1.26-1.68). The risk for serious adverse events was higher with orlistat 120 mg (RR = 2.63; 95% CI, 1.37-5.06) and semaglutide 2.4 mg (RR = 1.37; 95% CI, 1.1-1.72) than placebo. All of the medications in the study except for phentermine/topiramate were tied to higher risks for gastrointestinal adverse events than placebo, with the highest risk observed with naltrexone 32 mg/bupropion 360 mg.
The findings revealed tirzepatide and semaglutide are best for achieving the largest weight loss, but Majety said older obesity medications could still be used in some populations, especially among people whose insurance may not cover the newer medications or for those who have a contraindication to a GLP-1 receptor agonist.
“There are some patients with contraindications, [if] they may have pancreatitis or any family history of medullary thyroid cancers, we can’t use these medications, both tirzepatide and GLP-1s,” Majety told Healio. “If patients just cannot tolerate any doses or if they have gastroparesis, it just exacerbates the side effects. I do think that there are patients who would benefit from these older medications like phentermine/topiramate and naltrexone/bupropion. ... But if they don’t have any of those conditions, I think we should prioritize these newer injectable medications, which are such profound weight loss and metabolic benefits.”
Majety said the network meta-analysis was comprehensive, but more data are needed to assess the potential loss of lean body mass with obesity medications. More long-term safety data are also needed, according to Majety.
For more information:
Priyanka Majety, MD, can be reached at majetypriyanka@gmail.com.
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