Semaglutide is a Glucagon-like peptide-1 (GLP 1) analog that was first approved for the treatment of type 2 diabetes in adults. Semagludide (Ozempic) is given subcutaneously at doses up to 1 mg once a week, and recently an oral form of the drug (Rybelsus) has also been approved. In a global phase 3 trial funded by Novo Nordisk the drug’s manufacturer, the safety and efficacy of once weekly Semaglutide was evaluated for the treatment of overweight or obesity in adults without diabetes.
Of the current FDA approved drugs on the market for obesity, Phentermine is the most widely used of all. It is a sympathomimetic drug approved for short term use, a schedule IV drug, and the least expensive drug on the market. Phentermine-Topiramate ER combination provides greater efficacy, however, this drug is not approved for women of child-bearing age due to potential for adverse effects to the fetus. Other drugs on the market include Orlistat, a pancreatic and gastric lipase inhibitor, that is also available over the counter because of its low risk of long-term side effects; and Naltrexone-Bupropion combination, a drug that is contra-indicated in persons with underlying seizure disorders and hypertension. Fenfluramine, a serotonergic drug, was previously removed from the market in 1997 due to cardiac side effects, and a newer drug Lorcaserin is also to be withdrawn shortly due to an increased risk of cancer.
Anti-obesity drugs are not commonly prescribed in the US due to safety concerns and modest weight loss achieved by most patients.
GLP-1 receptor agonists are widely used in the treatment of type 2 diabetes. They are effective by decreasing glucose levels, increasing satiety and contribute to delayed gastric emptying and weight loss. Of the GLP-1 analogs on the market, Liraglutide is currently the only FDA approved GLP-1 drug for weight loss, it is given at 3 mg per day subcutaneously, and is one of the more expensive drugs on the market. Semaglutide is a human GLP‐1 analogue, and has a long half‐life of approximately one week, making it suitable for once‐weekly administration.
Glucagon‐like peptide (GLP)‐1, an incretin like hormone secreted from cells in the small intestine, stimulates insulin and inhibits glucagon secretions from the pancreatic islets in a glucose‐dependent fashion, reducing fasting and postprandial blood glucose levels. Additional effects include delay in gastric emptying, suppress appetite, enhance satiety and lower energy intake. GLP‐1 receptor agonists have been shown to reduce body weight and blood glucose levels in people who are overweight or obese, with or without diabetes.
According to data published recently in the New England Journal of medicine, a total 1961 adults were enrolled in this double-blind trial for a period of 68 weeks. Participants received 2.4 mg of Semaglutide subcutaneously once weekly. A mean weight loss of 14.9% was observed in the Semaglutide group compared with 2.4% in the placebo group, with 86% of the participants attaining at least 5% weight loss. The main reason for discontinuation of treatment was GI side effects, including nausea and vomiting. The company Novo Nordisk has filed for FDA regulatory approval of once weekly Semaglutide for treatment of obesity.
- Once-Weekly Semaglutide in Adults with Overweight or Obesity. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group.N Engl J Med. 2021 Mar 18;384(11):989. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
- Progress and challenges in anti-obesity pharmacotherapy. Bessesen DH, Van Gaal LF.Lancet Diabetes Endocrinol. 2018 Mar;6(3):237-248. doi: 10.1016/S2213-8587(17)30236-X. Epub 2017 Sep 14.
The question was prepared by Suparna Kumar MD, Certified Specialist in Poison Information (CSPI)
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