Drug Classes of Orlistat, Phentermine+Topiramate, and Semaglutide
Orlistat is a lipase inhibitor, phentermine+topiramate is a combination sympathomimetic/antiepileptic agent (adrenergic agonist + neurostabilizer), and semaglutide is a GLP-1 receptor agonist.
Orlistat
- Orlistat functions as a pancreatic and gastric lipase inhibitor, blocking approximately 30% of dietary fat absorption from the gastrointestinal tract 1.
- This medication reduces fat absorption by preventing triglycerides from being hydrolyzed, thereby decreasing absorption of free fatty acids 1.
- Orlistat was FDA-approved in 1999 for chronic weight management and remained the only approved weight loss medication for chronic use until 2012 1.
- It is available as prescription Xenical (120 mg) or over-the-counter Alli (60 mg), taken three times daily with meals containing fat 1.
Phentermine + Topiramate Extended-Release
- This fixed-dose combination consists of phentermine (an adrenergic agonist) and topiramate (a neurostabilizer/antiepileptic agent), approved by the FDA in 2012 as the first combination medication for chronic weight management 1.
Phentermine Component
- Phentermine is a sympathomimetic amine that promotes weight loss by activating the sympathetic nervous system through norepinephrine release 1, 2.
- This causes increased resting energy expenditure and appetite suppression 1.
- Phentermine has pharmacologic activity similar to amphetamines and is classified as a Schedule IV controlled substance 1.
Topiramate Component
- Topiramate's weight loss mechanism is mediated through modulation of gamma-aminobutyric acid receptors, inhibition of carbonic anhydrase, and antagonism of glutamate to reduce food intake by decreasing appetite and increasing satiation 1.
- Topiramate was originally approved for epilepsy in 1996 and migraine prophylaxis in 2004 1.
- The combination targets different pathways simultaneously for additive weight loss effects 1.
Semaglutide
- Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, a class of incretin-based medications 1.
- GLP-1 receptor agonists reduce appetite, increase satiety, and delay gastric emptying, leading to reduced food intake 1.
- Semaglutide 2.4 mg weekly (subcutaneous) was approved for chronic weight management and has demonstrated superior weight loss compared to other anti-obesity medications 1.
- This medication also has glucoregulatory benefits and is approved for treatment of type 2 diabetes mellitus at lower doses 1.
- The 2022 AGA guidelines suggest prioritizing semaglutide 2.4 mg over other approved anti-obesity medications for most patients given its magnitude of benefit 1.