By: Pauline Choi, PharmD

              There has been an increase in the prevalence of obesity, and it has become an international health problem amongst all age-groups, including children, adults, and adolescents. According to the World Health Organization (WHO), the definition of obesity for adults and children is a BMI > 30 kg/m², and a weight-for-height greater than 2-3 standard deviations above the WHO Child Growth Standards.⁴ Obesity is one of many risk factors for metabolic syndrome, which itself is not a disease, but rather a collection of risk factors. These risk factors include dyslipidemia, type 2 diabetes mellitus (T2DM) and hypertension (HTN).^2,5 As obesity is associated with both a widespread of diseases and a widespread of age groups, it is imperative that healthcare professionals direct their attention at addressing this pressing health issue.

On June 4, 2021, the Food and Drug Administration (FDA) approved Wegovy® (semaglutide) for chronic weight management. This medication is indicated for obese patients with a BMI > 30 kg/m² or overweight patients (BMI of > 25 kg/m²) with at least one weight-related comorbid condition (HTN, T2DM, dyslipidemia).² Obesity is a disease that can be prevented by making healthier food choices and engaging in regular physical activity.⁴ When patients lose 5-10% of body weight through diet and exercise, it is associated with a reduced risk of cardiovascular disease in patients with obesity.² Wegovy® should be used in addition to a reduced-calorie diet and increased physical activity to achieve optimal therapeutic outcomes.²

Wegovy® is a glucagon-like receptor agonist (GLP-1 RA), making it an incretin-based drug. When the GLP-1 receptor is prompted, it not only has a significant role in the stimulation of secreting insulin postprandially, but it also aids in enhancing satiety and delaying gastric emptying, eventually leading to decreased body weight.⁵ Prior to its approval for the treatment of obesity, semaglutide was previously indicated for the treatment of T2DM as a subcutaneous injection (Ozempic) and oral pill (Rybelsus). Wegovy® comes as a pre-filled, disposable, single-dose pen with a clear, colorless solution. The pen can deliver doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg.⁶

Wegovy® should be administered according to the dose-escalation schedule; starting with 0.25 mg injected subcutaneously once weekly and gradually increasing to 2.4 mg. However, if the patient is not able to tolerate a dose during the escalation period, consider delaying escalation for 4 weeks. The maintenance dose the patient would be on thereafter is 2.4 mg injected once weekly. If the patient does not tolerate the maintenance dose of 2.4 mg once weekly, the dose can be temporarily decreased to 1.7 mg once weekly for a maximum of 4 weeks.  After those 4 weeks, increase back to the maintenance dose, and if the patient is still unable to tolerate the maintenance dose, discontinue the medication. Some common side effects are nausea, diarrhea, vomiting, constipation, and abdominal pain. In  order to minimize gastrointestinal adverse reactions, it is recommended to follow the dose escalation schedule.⁶

              Safety and efficacy studies were conducted as four 68-week trials. Three of those studies were randomized, double-blind, placebo-controlled trials. The fourth study was a double-blind placebo-controlled, randomized withdrawal trial in which patients receiving Wegovy® either continued with the treatment or were switched to a placebo. More than 2,600 patients received Wegovy® and more than 1,500 patients received placebo. In study 1 (the largest trial), patients with diabetes were not included. The average body weight and BMI of the population was 231 pounds (105 kg) and 38 kg/m², respectively. Patients who received Wegovy® lost nearly 12.4% of their initial body weight on average compared to the patients who did not receive Wegovy® (95% CI -11.6 to -13.3). Study 2 included patients with diabetes, and the average body weight and BMI of this population was 220 pounds (100 kg) and 36 kg/m², respectively. In this study, patients who received Wegovy® lost about 6.2% of their initial body weight on average compared to those who did not receive Wegovy® (95% CI -5.2 to
-7.3).² Study 3 and 4 included patients classified as obese (BMI > 30 kg/m²) or overweight (BMI 25-29.9 kg/m²) and at least one weight-related comorbid condition; however, patients with T2DM were excluded. Study 3 randomized patients in a 2:1 ratio to receive either Wegovy® or placebo. In study 4, every patient received Wegovy® during the run-in period of 20 weeks, which included the 16 weeks of dose escalation, and then were randomized thereafter. Patients in study 3 who received Wegovy® lost about 10.3% of their initial body weight on average compared to those who got the placebo (95% CI -8.7 to -11.8). In study 4, patients lost about 14.8% of their initial body weight on average compared to those who received the placebo (95% CI -13.5 to -16.0).

         Contraindications to semaglutide include anyone with a history, whether familial or personal, of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Caution should be taken because of the potential risk of thyroid C-cell tumors. In rodents, semaglutide caused thyroid C-cell tumors that are dependent on dose and the length of treatment. It is vague as to whether the medication itself causes thyroid C-cell tumors in rodents as well as humans. Wegovy® also has a warning for acute pancreatitis. Both fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been seen in patients on GLP-1 receptor agonists, including Wegovy®. Signs and symptoms of acute pancreatitis include persistent severe abdominal pian, sometimes radiating to the back, which may or may not be accompanied by vomiting. Wegovy® should also not be prescribed in conjunction with other products containing semaglutide, other GLP-1 receptor agonists, or other weight loss products, including prescription drugs, over-the-counter medication, or herbal products.⁶

Wegovy® may be a great option to aid in the minimization and prevention of future health complications associated with obesity. As obesity becomes more prevalent, health care providers can find eligible candidates for Wegovy® to decrease the rates of obesity while also promoting lifestyle changes.

References

1. Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 2017;960:1-17. doi: 10.1007/978-3-319-48382-5_1
2. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014. Published June 4, 2021. Accessed February 4, 2022.
3. Metabolic syndrome. Metabolic syndrome – Better Health Channel. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/metabolic-syndrome. Published February 28, 2014. Accessed February 21, 2022.
4. Obesity and overweight. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Published June 9, 2021. Accessed February 4, 2022.
5. Perez-Montes DE Oca A, Pellitero S, Puig-Domingo M. Obesity and GLP-1. Minerva Endocrinol (Torino). 2021 Jun;46(2): 168-176. doi: 10.23736/S0391-1977.20.03369-6
6. Wegovy (Semaglutide) [package insert]. DK-2880 Bagsvaerd, Denmark; Novo Nordisk A/S; Revised 06/02/2021.

Published by Rho Chi Post