Are orlistat (Xenical, Alli) and setmelanotide (Imcivree) effective in the treatment of obesity?

Updated: Jun 09, 2021
  • Author: Osama Hamdy, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Orlistat blocks the action of pancreatic lipase, reducing triglyceride digestion and, thus, absorption. Two major clinical trials showed sustained weight loss of 9-10% over 2 years. [155] Orlistat’s effectiveness in producing weight loss does not depend on systemic absorption. The drug may reduce absorption of some fat-soluble vitamins (A, D, E, K) and beta-carotene, as well as absorption of some medications. Adverse effects include flatulence, fatty/oily stool, increased defecation, and fecal incontinence


Setmelanotide (Imcivree) is a melanocortin-4 agonist. It was approved by the FDA in November 2020 for patients aged 6 years or older for weight control in obesity caused by rare genetic conditions (eg, proopiomelanocortin [POMC], proprotein convertase subtilisin/kexin type 1 [PCSK1], leptin receptor [LEPR] deficiencies).  

Phase 3 clinical trials observed, after about 1 year of treatment, weight loss of at least 10% in 80% of patients with obesity caused by POMC or PCSK1 deficiency and in 45.5% of patients with obesity due to LEPR deficiency. Additionally, improvement was seen in hunger scores from baseline to 1 year. [126, 127]

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