Generic antiobesity drugs viable after successful weight loss with GLP-1 RA

Older-generation generic antiobesity medications (AOMs) for weight maintenance may be prescribed to patients who have achieved successful weight loss with glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy, suggests a study.

This finding suggests “potential cost savings for insurers and implications for policy regarding AOM coverage,” according to the researchers, noting that the high cost of novel GLP-1 RA class agents often prevents access to care.

One hundred five patients who had completed 1 year of therapy were prospectively reviewed. They were also part of a “medical weight loss bundle,” which included 12 months of GLP-1 RA therapy, followed by 6 months of transition care. Mean BMI at baseline was 36.4 kg/m². Researchers measured body weight outcomes at 6, 12, 18, and 24 months.

Of the patients, 40 transitioned to generic AOMs following the medical weight loss bundle. The most prescribed AOMs were metformin, topiramate, bupropion, and phentermine. These individuals lost an average of 18.3-percent (95 percent confidence interval [CI], 13.0–23.6) body weight at 1 year from baseline, having a mean BMI of 27.9 kg/m². [Obesity 2024;32:2255-2263]

Patients successfully maintained this weight loss at 18 months, with a mean BMI of 27.9 kg/m². In subsequent follow-up visits (average 1.5 months later) with no GLP-1 RA therapy, researchers observed further weight reduction, leading to a total average weight loss of 25.5 percent (95 percent CI, 23.1–27.9) compared to their very first visit.

Antiobesity agents

“The findings suggest that, after significant weight reduction, the body's decreased inflammation and insulin resistance may enhance its responsiveness to therapies such as metformin, topiramate, phentermine/topiramate, or bupropion,” the researchers said. 

“Given the current challenges of medication scarcity and insurance barriers, transitioning patients to economical AOMs emerges as a prudent alternative for long-term weight management in addition to maintaining a healthy lifestyle,” they added. 

Previous studies have shown that metformin helps to reduce weight by improving insulin resistance and promoting appetite suppression, while topiramate, an anticonvulsant, lowers the seizure threshold and acts as a γ-aminobutyric acid-A receptor agonist. [Nat Med 2015;21:506-511; Diabetologia 2016;59:1645-1654; https://www.ncbi.nlm.nih.gov/books/NBK482165/]

Bupropion also helps with weight loss maintenance through emotional eating and cravings reduction. It does this by serving as a dopamine and norepinephrine reuptake inhibitor and by reducing the reward associated with food intake. [https://www.ncbi.nlm.nih.gov/books/NBK470212/]

Phentermine, on the other hand, is a sympathomimetic agent that increases norepinephrine and epinephrine levels, which suppress appetite and boost energy expenditure. [Obesity 2024;32:2255-2263]

“Patients who respond well to GLP-1 RA therapy within the first year may be suitable candidates for transitioning to generic AOMs,” the researchers said. “Clinicians should discuss the benefits, risks, and cost-effectiveness of transitioning from expensive GLP-1 RA medications to oral generics.”

Inflammation

Earlier studies have shown how obesity mediates systemic inflammation, which potentially induces insulin resistance and makes weight loss difficult to sustain. Obesity is also associated with high rates of plasma fatty acid mobilization and uptake, which contribute to the development of insulin resistance. [Sci Transl Med 2023;15:eadf9382; J Physiol 2009;587:4949-4961]

“However, with significant weight loss, particularly a combination of healthy dietary modifications, GLP-1 RA therapy, and an increase in physical activity, there is a reduction in fatty acid mobilization and uptake, which is a key process in reducing insulin resistance,” the researchers said.