Wegovy® (semaglutide 2.4mg once weekly)

Wegovy^® is a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for people living with obesity. It has been approved for use by the UK, US, Europe, and Canada and several other health authorities based on the results from the STEP trials. On 31 August 2021, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) approved Wegovy^® for chronic weight management. Due to supply constraints, Wegovy^® became available to prescribe in the UK in September 2023. Supply is expected to be constrained into 2024.

 

Wegovy^® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with an initial Body Mass Index (BMI) of: ≥30 kg/m2 (obesity), or ≥27 kg/m2 to <30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity.

Please review the Related Co-morbidities topic in The Science of Obesity Lesson.

The MHRA approval for Wegovy^® for chronic weight management is supported by the results of the STEP (Semaglutide Treatment Effect in People with obesity) phase 3a clinical trial programme, which included more than 4,500 adults with obesity or overweight. Across the STEP programme, people with obesity treated with semaglutide 2.4mg achieved greater reduction in body weight from baseline compared to placebo, with an average weight loss of 15% sustained over 68 weeks. The global clinical phase 3a programme consists of four trials in adults and has enrolled approximately 5,000 people with overweight or obesity across over 15 countries, including the US, the UK, Canada, Japan, Mexico, Germany, and France.

 

Clinical Studies for Wegovy^®:

STEP Trials

Key results from each trial:

STEP 1:

Weight loss occurred early and continued throughout the trial. At the end of treatment (week 68), weight loss was superior and clinically meaningful compared with placebo. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide 2.4mg group as compared with −2.4% with placebo (95% confidence interval [CI], −13.4 to −11.5; P<0.0001). Furthermore, a higher proportion of patients achieved ≥5%, ≥10%, ≥15% and ≥20% weight loss with semaglutide 2.4mg compared with placebo.

 

STEP 2:

Treatment with semaglutide 2.4mg for 68 weeks resulted in superior and a clinically meaningful reduction in body weight and in HbA1c compared to placebo. The mean change in body weight from baseline to week 68 was –9.6% for
semaglutide 2.4mg as compared with –3.4% for placebo [95%CI, −7.3 to −5.2]; P < 0.0001). In STEP 2, after approximately 6 months (28 weeks) of treatment, 74.7% of patients treated with semaglutide 2.4mg achieved a ≥5% weight loss. Out of those who did not, 31.9% achieved a weight loss ≥5% at week 68 of treatment.

STEP 3:

Treatment with semaglutide 2.4mg and intensive behavioural therapy (IBT) for 68 weeks resulted in superior and clinically meaningful reduction in body weight compared to placebo. The mean change in body weight from baseline to week 68 was –16.0% for semaglutide 2.4mg as compared with –5.7% for placebo, for an estimated treatment difference of −10.3 percentage points [95%CI, −12.0 to −8.6]; P < 0.0001)

STEP 4:

 Patients who had reached the maintenance dose of 2.4mg at week 20 (baseline) and continued treatment with semaglutide 2.4mg for 48 weeks (week 20–68) continued losing weight and had a superior and clinically meaningful reduction in body weight compared to those switched to placebo. The mean change in body weight from week 20 to week 68 was –7.9% for semaglutide 2.4mg as compared with +6.9% for placebo [95%CI, −16.0 to −13.5]; P < 0.0001).

STEP 5:

The objective of the STEP 5 trial was to show superiority of semaglutide 2.4mg versus placebo on weight loss and to compare safety and tolerability in adults with obesity or overweight after two years of treatment.

In this 104-week, double-blind trial, 304 patients with obesity (BMI ≥30 kg/m2), or with overweight (BMI ≥27 kg/m2 to <30 kg/m2) and at least one weight-related comorbidity were randomised to semaglutide 2.4mg or placebo. All patients were on a reduced-calorie diet and increased physical activity throughout the trial.

Similar percentage weight loss was seen over all BMI categories.

Safety profile of Wegovy^® in the STEP 1–5 trials:

In the STEP trials, semaglutide 2.4mg was generally well-tolerated both in adults with obesity, or overweight with comorbidities, and without type 2 diabetes (STEP 1, 3 and 4), and in adults with type 2 diabetes and overweight or obesity (STEP 2). The most common adverse events among people treated with semaglutide 2.4mg were gastrointestinal events. Most events were transient, and mild or moderate in severity and resolved without permanent treatment discontinuation.

Listed adverse reactions:

• Very common (≥1/10)*: headache, vomiting, diarrhoea, constipation, nausea, abdominal pain, fatigue
• Common (≥1/100 to <1/10): hypoglycaemia in patients with T2D, dizziness*, diabetic retinopathy in patients with T2D, hair loss, gastritis*, gastroesophageal reflux disease*, dyspepsia*, eructation*, flatulence*, abdominal distension*, cholelithiasis, injection site reactions
• Uncommon (≥1/1,000 to <1/100): increased heart rate, acute pancreatitis, increased amylase, increased lipase
• Rare (≥1/10,000 to <1/1,000): anaphylactic reaction, angioedema

*Mainly seen in the dose-escalation period.

For details of full Adverse Events and special precautions please refer to Wegovy®  SmPC available here.

Wegovy® should not be used during pregnancy or breastfeeding

NICE recommendation

NICE has recommended Wegovy^® for weight management, including weight loss and weight maintenance, alongside a reduced calorie diet and increased physical activity in adults, only if:

1. it is used for a maximum of 2 years, and within a specialist weight management service providing multidisciplinary management of overweight or obesity (including but not limited to tiers 3 and 4), and:
2. They have at least one weight-related comorbidity and:
3. A body mass index (BMI) at least 35.0kg/m2 or a BMI of 30.0 kg/m2 to 34.9kg/m2 if they are referred to tier 3 services based on the criteria in NICE’s clinical guideline on obesity: identification, assessment, and management.

NICE’s recommendation only applies to the NHS in England and Wales. In Scotland, the Scottish Medicines Consortium (SMC) submission is complete. A final decision for Wegovy^® by the SMC is pending.

Should my patient expect weight regain when going off Wegovy®?

Results from the STEP trials demonstrate that weight regain is likely once medication is stopped. Clinical experts view obesity as a chronic disease that should be managed similar to other long-term health conditions such as diabetes and hypertension.

Wegovy® should be used as part of a lifestyle change to support long term health improvement for patients. It should not be used as a quick fix as when a patient goes off Wegovy® and return to their ‘normal’ level of appetite (and calorie consumption) they should expect to gain weight. A pharmaceutical intervention should be prescribed as part of a program to improve overall health. As a private medical practitioner, you can provide a program to educate and support your patient to improve their lifestyle and health therefore improving their confidence.

References:

1. EMA. Wegovy^® Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/wegovy-epar-product-information_en.pdf
2. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity. 2020; 28:1050-1061.

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