Is Ozempic (semaglutide) indicated for non-diabetic patients?

From the Guidelines

Ozempic (semaglutide) is indicated for non-diabetic patients for chronic weight management, as evidenced by the most recent and highest quality study 1.

Key Points

• The medication is approved for adults without type 2 diabetes (T2D) for chronic weight management, with a typical starting dose of 0.25 mg injected subcutaneously once weekly for the first month, then increased to 0.5 mg weekly for at least one month, and if needed and tolerated, the dose can be increased to 1 mg weekly or higher doses as indicated for Wegovy.
• The FDA indication for all medications, including Ozempic, is a BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with significant complications.
• Common side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation, which often improve over time.
• Patients should be counseled that Ozempic must be used alongside lifestyle modifications including diet and exercise for optimal results.
• It's contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, and caution is advised in those with pancreatitis history.
• Regular monitoring for side effects and effectiveness is essential, with treatment continuation evaluated based on achieving at least 5% weight loss within 3-6 months, as supported by studies such as the STEP trials 1.

Mechanism of Action and Benefits

• Ozempic works by mimicking GLP-1, a hormone that regulates appetite and food intake, helping patients feel fuller longer and consume fewer calories.
• The medication has been shown to reduce weight and improve weight-related comorbidities significantly, and decrease the risk of cardiovascular events in adults with overweight or obesity without diabetes, as demonstrated in the SELECT study 1.

Clinical Considerations

• The use of Ozempic in non-diabetic patients should be considered on a case-by-case basis, taking into account the patient's individual needs and medical history.
• Patients should be closely monitored for side effects and effectiveness, and treatment should be adjusted or discontinued as necessary.
• Lifestyle modifications, including diet and exercise, are essential for optimal results and should be encouraged and supported throughout treatment.

From the Research

Indication for Non-Diabetic Patients

• Ozempic (semaglutide) is primarily approved for the treatment of type 2 diabetes, but its use has expanded to include weight management in non-diabetic patients 2, 3, 4, 5.
• Studies have shown that semaglutide can be used safely and efficiently in non-diabetic people with excess weight, providing a new milestone in the pharmacological treatment of obesity 3.
• The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme has evaluated once-weekly subcutaneous semaglutide 2.4 mg in people with overweight or obesity, including those without type 2 diabetes, and found significant weight loss and improvements in cardiometabolic risk factors 4, 5.

Off-Label Prescribing

• Although not approved for weight loss without type 2 diabetes, one-third of new users in 2022 did not have type 2 diabetes, indicating off-label prescribing for weight loss 2.
• However, most initiators with type 2 diabetes had a clear medical indication for treatment intensification, and "off-label" use can only explain a minor part of the supply shortage 2.

Efficacy and Safety

• Semaglutide has been shown to be effective in individuals with baseline BMI <35 and ≥35 kg/m2, including those with comorbidities, prediabetes, and high risk of cardiovascular disease 5.
• The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events 4.