Semaglutide for Weight Management

Semaglutide is a glucagon-like peptide 1 (GLP-1) agonist originally approved for managing type 2 diabetes. Glucagon-like peptide 1 is an incretin hormone that stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner. Semaglutide can produce significant clinical benefits in diabetes management, including reduced HbA_1c and lower fasting and postprandial glucose levels.

Glucagon-like peptide 1 agonists are also associated with weight loss due to an increase in satiety and a slowing of gastric emptying. As weight loss with these agents can be significant, semaglutide has been used off-label as a weight loss therapy. An unfortunate consequence of this is a long-term supply interruption as manufacturers struggled to meet the increased demand. The supply interruption for Ozempic® (semaglutide) is anticipated to continue until the end of 2024. However, a new brand of semaglutide is now marketed and available in Australia.

Wegovy® (semaglutide) is indicated for weight management as an adjunct to diet and exercise. While Wegovy® and Ozempic® contain the same active ingredient, they have different dosages and administration devices and should not be considered interchangeable. A comparison of the two presentations is shown in Table 1.

Table 1. Comparison of Ozempic® and Wegovy®

 Semaglutide for weight management

Use and administration:

In adults, Wegovy® is indicated for chronic weight management (including weight loss and weight maintenance) in people with an initial body mass index (BMI) of:

• ≥30 kg/m² (obesity); or
• ≥27 kg/m² to <30 kg/m² (overweight) who have at least one weight-related comorbidity.

In adolescents, Wegovy® is indicated for weight management in people 12 years and above with initial obesity (BMI ≥ 95th percentile) and a body weight above 60 kg. The manufacturer recommends discontinuation of treatment in adolescent patients if the BMI does not reduce by at least 5% after 12 weeks on the 2.4mg dose (or the maximum tolerated dose).

Presentation and use:

Wegovy® is presented in a FlexTouch® pen device for subcutaneous injection. A pack contains one pen, with each pen containing four doses. Wegovy® should be refrigerated before use but may be stored at room temperature (up to 30°C) after first use for up to 42 days. The pen should always be stored without the needle attached.

For weight management, the recommended maintenance dose of semaglutide is 2.4mg weekly. To minimise the impact of gastrointestinal adverse effects, gradual dose escalation is required. Wegovy® is available in five strengths to aid this dose escalation process. The dosing schedule recommended by the manufacturer is shown in Table 2.

Table 2. Wegovy® dose escalation schedule

 Efficacy:

A double-blind, double-dummy study investigated the efficacy of semaglutide for weight management in adults with overweight or obesity and type 2 diabetes. Semaglutide 1mg weekly (i.e. the usual maintenance dose for type 2 diabetes) and semaglutide 2.4mg weekly (i.e. the recommended maintenance dose for weight management) were compared with placebo.

Patients in the semaglutide 2.4mg group achieved a 9.6% reduction in body weight over the 68-week trial period. This is in comparison to a 6.99% reduction in the semaglutide 1mg group and a 3.42% reduction in the placebo group.

Both semaglutide doses demonstrated superiority over placebo for various metabolic parameters. Semaglutide 2.4mg and 1mg doses delivered similar HbA_1c reductions (1.6% vs 1.5%, respectively) that were superior to the placebo group (0.4% reduction). Semaglutide was also associated with improved blood lipid profiles and reduced systolic blood pressure.

Adverse effects

All GLP-1 agonists are associated with gastrointestinal adverse effects. Nausea, vomiting, diarrhoea, constipation, and abdominal pain are very common with semaglutide. These adverse effects are typically mild to moderate in severity and transient in nature. The median duration of nausea, vomiting, and diarrhoea in clinical trials was between two and eight days. Constipation may persist for longer, with trials reporting a median duration of 47 days. Gastrointestinal adverse effects led to permanent discontinuation in only 4.3% of trial participants.

Patients should be counselled on the likelihood of experiencing these adverse effects and given strategies on how to manage them. General counselling points to minimise the impact of gastrointestinal adverse effects may include advice on the following:

• Eating habits
  • Eat slowly
  • Only eat when hungry
  • Eat smaller portions more frequently
  • Avoid lying down immediately after a meal
• Food composition
  • Choose low-fat, easy-to-digest foods
  • Increase fluid intake (i.e. small, regular sips of clear drinks)
• Food diary
  • May help to identify foods or eating habits that contribute to the condition.

More specific advice may also be required for patients experiencing particular adverse effects. For example, patients experiencing constipation should ensure they have adequate fibre in their diet, increase their physical activity, and be encouraged to remain well hydrated. On the other hand, patients experiencing diarrhoea may need to temporarily reduce their fibre intake.

Providing patients with realistic expectations and strategies to minimise adverse effects may help improve adherence to therapy. However, patients should be encouraged to speak to their prescriber if adverse effects are persistent or particularly troublesome.