From the Guidelines
The most effective GLP-1 receptor agonist currently available is semaglutide, as evidenced by its superior cardiovascular outcomes and glycemic control in clinical trials, such as the SUSTAIN-6 trial 1. The effectiveness of semaglutide stems from its long half-life of approximately one week, which allows for convenient once-weekly dosing while maintaining consistent blood levels. Semaglutide has demonstrated a significant reduction in cardiovascular events, with a hazard ratio of 0.74 [95% CI 0.58–0.95] compared to placebo in the SUSTAIN-6 trial 1. Some key points to consider when prescribing semaglutide include:
- Starting with a lower dose (0.25mg for Ozempic) and gradually increasing to the therapeutic dose (typically 1.0mg for diabetes or 2.4mg for weight management) to minimize gastrointestinal side effects
- Common side effects include nausea, vomiting, diarrhea, and constipation, which typically improve over time
- Semaglutide works by mimicking the incretin hormone GLP-1, which stimulates insulin secretion, suppresses glucagon release, slows gastric emptying, and reduces appetite through central nervous system effects
- The oral formulation of semaglutide has also been shown to be noninferior to placebo for the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the PIONEER 6 trial 1. Overall, semaglutide is a highly effective GLP-1 receptor agonist that offers superior cardiovascular outcomes and glycemic control, making it a valuable treatment option for patients with type 2 diabetes.
From the FDA Drug Label
INDICATIONS AND USAGE OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as: • an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1). • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease (1).
The most effective GLP-1 cannot be determined from the provided information, as efficacy comparisons between different GLP-1 receptor agonists, such as semaglutide and dulaglutide, are not directly addressed in the given drug labels 2.
From the Research
GLP-1 Receptor Agonists
- GLP-1 receptor agonists (GLP-1 RAs) are a class of glucose-lowering agents that have been developed to treat type 2 diabetes 3.
- They work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 3.
- GLP-1 RAs are available in various formulations, including injectable and oral preparations, with different dosing frequencies, such as twice daily, once daily, or once weekly 3, 4.
Efficacy and Safety
- Studies have shown that GLP-1 RAs are effective in reducing HbA1c levels and body weight, with a low risk of hypoglycemia 3, 4, 5.
- Long-acting GLP-1 RAs, such as liraglutide, once-weekly exenatide, dulaglutide, albiglutide, and semaglutide, have more profound effects on overnight and fasting plasma glucose and HbA1c levels 3.
- Semaglutide, in particular, has been shown to have greater efficacy in lowering plasma glucose and body weight, with a low risk of hypoglycemia 6, 7.
Cost-Effectiveness
- A cost-effectiveness analysis found that oral semaglutide 14 mg was likely to be cost-effective compared to other GLP-1 RAs, such as dulaglutide, exenatide, liraglutide, and lixisenatide, in terms of bringing patients with type 2 diabetes to glycemic control targets 5.
Clinical Use
- GLP-1 RAs are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment, due to their efficacy and safety profile 3.
- Oral semaglutide has been shown to be effective and safe in patients with type 2 diabetes who are considered for injectable GLP-1 RA therapy or are currently on insulin therapy 7.