Wegovy Adverse Reactions

Summary of safety profile: In four phase 3a trials, 2,650 adult patients were exposed to Wegovy. The duration of the trials were 68 weeks. The most frequently reported adverse reactions were gastrointestinal disorders including nausea, diarrhoea, constipation and vomiting.
Tabulated list of adverse reactions: Table 12 lists adverse reactions identified in clinical trials in adults and post-marketing reports. The frequencies are based on a pool of the phase 3a trials.
Adverse reactions associated with Wegovy are listed by system organ class and frequency. Frequency categories are defined as: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data). (See Table 12.)

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Description of selected adverse reactions: The following information on specific adverse reactions, unless otherwise specified, pertains to the phase 3a trials.
Gastrointestinal adverse reactions: Over the 68 weeks trial period, nausea occurred in 43.9% of patients when treated with semaglutide (16.1% for placebo), diarrhoea in 29.7% (15.9% for placebo) and vomiting in 24.5% (6.3% for placebo). Most events were mild to moderate in severity and of short duration. Constipation occurred in 24.2% of patients treated with semaglutide (11.1% for placebo) and was mild to moderate in severity and of longer duration. In patients treated with semaglutide, median duration of nausea was 8 days, vomiting 2 days, diarrhoea 3 days, and constipation 47 days.
Patients with moderate renal impairment (eGFR ≥30 to <60 mL/min/1.73m²) may experience more gastrointestinal effects when treated with semaglutide.
The gastrointestinal events led to permanent treatment discontinuation in 4.3% of patients.
Acute pancreatitis: The frequency of adjudication-confirmed acute pancreatitis reported in phase 3a clinical trials was 0.2% for semaglutide and <0.1% for placebo, respectively. In SELECT, the cardiovascular outcomes trial, the frequency of acute pancreatitis confirmed by adjudication was 0.2% for semaglutide and 0.3% for placebo.
Acute gallstone disease/Cholelithiasis: Cholelithiasis was reported in 1.6% and led to cholecystitis in 0.6% of patients treated with semaglutide. Cholelithiasis and cholecystitis was reported in 1.1% and 0.3%, respectively, of patients treated with placebo.
Hair loss: Hair loss was reported in 2.5% of patients treated with semaglutide and in 1.0% of patients treated with placebo. The events were mainly of mild severity and most patients recovered while on continued treatment. Hair loss was reported more frequently in patients with a greater weight loss (≥20%).
Increased heart rate: In the phase 3a trials, a mean increase of 3 beats per minute (bpm) from a baseline mean of 72 bpm was observed in patients treated with semaglutide. The proportions of subjects with an increase in pulse from baseline ≥10 bpm at any timepoint during the on-treatment period were 67.0% in the semaglutide group vs. 50.1% in the placebo group.
Immunogenicity: Consistent with the potentially immunogenic properties of medicinal products containing proteins or peptides, patients may develop antibodies following treatment with semaglutide. The proportion of patients testing positive for anti-semaglutide antibodies at any time post-baseline was low (2.9%) and no patients had anti-semaglutide neutralising antibodies or anti-semaglutide antibodies with endogenous GLP-1 neutralising effect at end-of-trial. During treatment, high semaglutide concentrations might have lowered the sensitivity of the assays, hence the risk of false negatives cannot be excluded. However, in subjects testing positive for antibodies during and after treatment, the presence of antibodies was transient and with no apparent impact on efficacy and safety.
Hypoglycaemia in patients with type 2 diabetes: In STEP 2, clinically significant hypoglycaemia was observed in 6.2% (0.1 events/patient year) of subjects treated with semaglutide compared with 2.5% (0.03 events/patient year) of subjects treated with placebo. Hypoglycaemia with semaglutide was seen both with and without concomitant use of sulfonylurea. One episode (0.2% of subjects, 0.002 events/patient year) was reported as severe in a subject not concomitantly treated with a sulfonylurea. The risk of hypoglycaemia was increased when semaglutide was used with a sulfonylurea.
In STEP-HFpEF-DM, clinically significant hypoglycaemia was observed in 4.2% of subjects in both the semaglutide and placebo groups when used in combination with sulfonylurea and/or insulin (0.065 events/patient year with semaglutide and 0.098 events/patient year with placebo).
Diabetic retinopathy in patients with type 2 diabetes: A 2-year clinical trial investigated semaglutide 0.5 mg and 1 mg vs. placebo in 3,297 patients with type 2 diabetes, with high cardiovascular risk, long duration of diabetes and poorly controlled blood glucose. In this trial, adjudicated events of diabetic retinopathy complications occurred in more patients treated with semaglutide (3.0%) compared to placebo (1.8%). This was observed in insulin-treated patients with known diabetic retinopathy. The treatment difference appeared early and persisted throughout the trial. In STEP 2, retinal disorders were reported by 6.9% of patients treated with Wegovy, 6.2% of patients treated with semaglutide 1 mg, and 4.2% of patients treated with placebo. The majority of events were reported as diabetic retinopathy (4.0%, 2.7%, and 2.7%, respectively) and non-proliferative retinopathy (0.7%, 0%, and 0%, respectively).
Dysaesthesia: Events related to a clinical picture of altered skin sensation such as paraesthesia, pain of skin, sensitive skin, dysaesthesia and burning skin sensation were reported in 2.1% of patients treated with semaglutide 2.4 mg and 1.2% of patients treated with placebo. The events were mild to moderate in severity and most patients recovered while on continued treatment.
Paediatric population: In a clinical trial conducted in adolescents of 12 years to below 18 years with obesity or overweight with at least one weight-related comorbidity, 133 patients were exposed to Wegovy. The trial duration was 68 weeks.
Overall, the frequency, type and severity of adverse reactions in the adolescents were comparable to that observed in the adult population. Cholelithiasis was reported in 3.8% of patients treated with Wegovy and 0% of patients treated with placebo.
No effects on growth or pubertal development were found after 68 weeks of treatment.
Other special populations: In the SELECT and SUSTAIN 6 trials, in adults with established cardiovascular disease, the adverse reaction profile was similar to that seen in the weight management phase 3a trials.
In the HFpEF trials, in adults with obesity related heart failure with preserved ejection fraction (HFpEF), the adverse reaction profile was similar to that seen in the weight management phase 3a trials.