Semaglutide is a Promising Drug Treatment for Chronic Weight Management

According to the CDC, the prevalence of obesity in adults in the United States rose from 35% in 2017 to 2018 to 42.4% in 1999 to 2000. Diabetes mellitus, cardiovascular disease, osteoarthritis, and certain cancers

On June 4, 2021, the FDA approved semaglutide (Wegovy; Novo Nordisk) for the treatment of chronic weight management in adults. 3 semaglutide, available in strengths of 0.25, 0.5, 1.0, 1.7 and 2, 4 mg for titration purposes, is a once-weekly subcutaneous injection approved for use in obese or overweight adults with at least one other weight-related disorder – such as type 2 diabetes, hypertension, or dyslipidemia – in addition to the recommended lifestyle choices 3 Such measures include a reduced calorie diet, such as setting a 500 kcal deficit per day and an average of 150 minutes of physical activity per week. 4

In 2017, semaglutide (Ozempic; Novo Nordisk) was approved by the FDA for the treatment of type 2 diabetes mellitus in doses of up to 1 mg subcutaneously once a week.5 A glucagon-like peptide 1 receptor agonist (GLP- 1 RA), semaglutide was evaluated in the studies of semaglutide treatment efficacy in people with obesity (STEP) at a maintenance dose of 2.4 mg once a week subcutaneously. 4

In the double-blind STEP-1 study, 1961 adults with a body mass index (BMI) of 30 kg / m2 or more or a BMI of 27 kg / m2 or more, with at least one weight-related disease and without type 2 Diabetes mellitus. The study participants were 74% women with an average age of 46 years and an average body weight of 105 kg.

During the study, participants received either a weekly injection of 2.4 mg semaglutide or a placebo in addition to lifestyle interventions for 68 weeks. Participants who received semaglutide therapy showed an average weight loss of 14.9% from baseline compared to 2.4% in the placebo group

The STEP 2 phase 3 study also evaluated the efficacy and safety of semaglutide in obese or overweight adults with at least one weight-related disorder, but included patients with diabetes.5 Study participants had mean hemoglobin A1c levels of 7% up to 10% and an average body weight of 99 kg. At week 68, the weight reduction was 9.6% with semaglutide for a weekly injection of 2.4 mg versus 3.4% with placebo. 6

During the STEP 3 study, investigators specifically looked at the effects of semaglutide in a once-weekly injection of 2.4 mg alongside intensive behavioral therapy and an initial low-calorie diet in obese or overweight patients. In the STEP 3 study, participants took part in 30 counseling visits compared to 18 counseling visits in the STEP 1 study. At week 68, patients in the semaglutide group in the STEP 3 study experienced a 16% weight loss versus 5.7% in the placebo group. 7

During the STEP 4 study, researchers looked at the effects of long-term treatment. Patients received 2.4 mg semaglutide once a week for the first 20 weeks, resulting in an average weight loss of 10.6%, and were randomly assigned to continue treatment or to placebo for the next 48 weeks. Participants who continued to receive semaglutide lost an additional 7.9% of their body weight versus the placebo group, who regained an average of 6.9% of their body weight

The side effects (AEs) most frequently reported in both studies were relatively similar and mostly gastrointestinally related, such as nausea, vomiting, diarrhea and constipation. 4.6 AEs occurred more frequently with 74.2% in the semaglutide group than in the placebo group. Group. compared to 47.9% and 4

For the STEP 1 study, the researchers stated that the majority of gastrointestinal AEs were mild to moderate in severity and ultimately healed without discontinuing therapy. Ozempic has been used in patients with type 2 diabetes since 2017 under the trade name Ozempic.

When compared to liraglutide (Saxenda; Novo Nordisk), a daily injectable GLP-1-RA approved by the FDA for weight loss in 2014, a similar safety profile to semaglutide was found; However, the mean weight loss reported in clinical trials was 8.4 ± 7.3 kg body weight at 56 weeks in the liraglutide group versus 2.8 ± 6.5 kg in the placebo group.10

In addition, a meta-analytical study found that the risk of non-compliance with daily dosing was 11% higher than with once-weekly dosing.11 This could suggest that greater numbers of patients are willing to adhere to weekly therapies compared to daily, especially when it comes to an injectable drug.

Other FDA-approved anti-obesity drugs are given more frequently, such as bupropion / naltrexone (Contrave; Nalpropion Pharmaceuticals) twice a day as a maintenance dose, or orlistat (Xenical or Alli; CHEPLAPHARM and H2-Pharma) up to three times a day. However, the more frequent dosing regimen with bupropion / naltrexone or orlistat may limit patient adherence and acceptance. Orlistat also has undesirable AE, including oily spots, urge to defecate, greasy stools, and oily bowel movements.12,13


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  11. Weeda ER, Muraoka AK, Brock MD, Cannon JM. Drug adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly or once daily in patients with type 2 diabetes: a meta-analysis. Int J Clin Pract. 2021 February 1; e14060.
  12. Xenisch. [package insert]. The Food and Drug Administration. Roche Laboratories Inc. 1999.
  13. Bupropion / naltrexone. In: Clinical Pharmacology powered by ClinicalKey [database on the Internet]. Tampa (FL): Elsevier; 2021 [updated 2020 Aug 7; 2021 Aug 7].

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