Indications for: WEGOVY
As an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in: adults with an initial body mass index (BMI) of ≥30kg/m2 (obese) or ≥27kg/m2 (overweight) in the presence of at least 1 weight-related comorbid condition (eg, hypertension, T2DM, dyslipidemia); and pediatric patients with an initial BMI at the 95th percentile or greater standardized for age and sex (obesity).
Limitations of Use:
Do not use with other semaglutide-containing products or with any other GLP-1 receptor agonist. Safety and efficacy have not been established with other products intended for weight loss, including prescription drugs, OTC drugs, and herbal preparations. Not studied in those with a history of pancreatitis.
The approval was based on three 68-week double-blind, placebo-controlled studies (Studies 1, 2, 3), in which Wegovy or placebo was escalated to 2.4mg subcutaneous weekly during a 16-week period followed by 52 weeks on maintenance dose, as well as one 68-week withdrawal trial (Study 4), in which Wegovy was escalated during a 20-week run-in period, and patients who reached 2.4mg after the run-in period were randomly assigned to either continue treatment or placebo for 48 weeks.
In Studies 1, 2, and 3, the primary efficacy endpoints were mean percent change in body weight and the percentages of patients achieving greater than or equal to 5% weight loss from baseline to week 68. Findings from these studies showed that treatment with Wegovy resulted in statistically significant reductions in body weight, with a greater proportion of patients achieving 5%, 10%, and 15% weight loss, compared with placebo.
Study 1 (ClinicalTrials.gov Identifier: NCT03548935) included 1961 patients with obesity or with overweight and at least 1 weight-related comorbid condition; mean baseline body weight was 105.3 kg and mean BMI was 37.9 kg/m2. Wegovy-treated patients (n=1306) lost an average of 12.4% (95% CI, -13.3, -11.6) of their initial body weight compared with those who received placebo (n=655) (P <.0001).
Study 2 (ClinicalTrials.gov Identifier: NCT03552757) enrolled 807 patients with type 2 diabetes and a BMI of at least 27 kg/m2; mean baseline body weight was 99.8 kg and mean BMI was 35.7 kg/m2. In this study, patients who received Wegovy (n=404) lost an average of 6.2% (95% CI, -7.3, -5.2) of their initial body weight compared with placebo (n=403) (P <.0001).
Study 3 (ClinicalTrials.gov Identifier: NCT03611582) included 611 patients with obesity or with overweight and at least 1 weight-related comorbid condition who were undergoing intensive lifestyle therapy; mean baseline body weight was 105.8 kg and mean BMI was 38.0 kg/m2. Findings showed that Wegovy-treated patients (n=407) lost an average of 10.3% (95% CI, -11.8, -8.7) of their initial body weight compared with placebo (n=204) (P <. 0001).
In Study 4 (ClinicalTrials.gov Identifier: NCT03548987), the primary efficacy measure was mean percent change in body weight from randomization (week 20) to week 68. The mean body weight change was observed to be -7.9% with continued Wegovy treatment vs +6.9% with placebo (% difference from placebo, -14.8 [95% CI, -16.0, -13.5]; P <.001).
Adults and Children:
<12yrs: not established. Give by SC inj in abdomen, thigh, or upper arm; rotate inj sites. ≥12yrs: Escalate dose with the following schedule (to minimize GI effects): Weeks 1–4: 0.25mg once weekly; Weeks 5–8: 0.5mg once weekly; Weeks 9–12: 1mg once weekly; Week 13–16: 1.7mg once weekly; Week 17 and onward: 2.4mg once weekly (in children ≥12yrs), and 2.4mg (recommended) or 1.7mg once weekly in adults. Consider delaying dose escalation for 4 weeks if increased dose not tolerated. If the maintenance 2.4mg once-weekly dose is not tolerated, may reduce to 1.7mg once weekly. For children ≥12yrs: discontinue if the 1.7mg dose is not tolerated.
History (personal or family) of medullary thyroid carcinoma. Multiple endocrine neoplasia syndrome type 2.
Risk of thyroid C-cell tumors.
Risk of thyroid C-cell tumors; inform patients of potential risk and symptoms. Monitor for acute pancreatitis; discontinue if suspected; do not restart if confirmed. History of pancreatitis. Acute gallbladder disease. Monitor renal function when initiating or escalating doses, or in renal impairment. History of diabetic retinopathy; monitor for progression. History of suicidal attempts or ideation: avoid. Monitor for emergence or worsening depression, suicidal thoughts or behavior; discontinue if occurs. Monitor blood glucose prior to and during treatment in those with T2DM. Monitor heart rate periodically; discontinue if sustained increases. History of anaphylaxis or angioedema with other GLP-1 receptor agonist. Discontinue if hypersensitivity reactions occur. Pregnancy. Females of reproductive potential: discontinue ≥2 months prior to planned pregnancy. Nursing mothers.
Glucagon-like peptide-1 (GLP-1) receptor agonist.
Increased risk of hypoglycemia with concomitant insulin secretagogues (eg, sulfonylureas) or insulin; may need a lower dose of these. May affect absorption of other oral drugs (delayed gastric emptying); caution.
Nausea, diarrhea, vomiting, constipation, abdominal pain/distension, headache, fatigue, dyspepsia, dizziness, eructation, hypoglycemia in T2DM, flatulence, gastroenteritis, GERD, nasopharyngitis; acute kidney injury, retinal disorders, lab abnormalities (eg, increased lipase or amylase), hypersensitivity reactions.
With an elimination half-life of ~1 week, semaglutide will be present in the circulation for about 5 to 7 weeks after the last dose of 2.4 mg.
The primary excretion routes of semaglutide-related material are via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide.
Generic Drug Availability:
Single-dose prefilled pens—4