From the Guidelines
GLP-1 receptor agonists are a valuable treatment option for patients with type 2 diabetes, offering benefits beyond glucose control, including weight loss and cardiovascular protection, as evidenced by the LEADER trial which showed a 13% reduction in cardiovascular events 1.
Key Points
- GLP-1 receptor agonists mimic the action of glucagon-like peptide-1, a hormone that helps regulate blood sugar levels.
- Common GLP-1 receptor agonists include semaglutide, dulaglutide, liraglutide, exenatide, and tirzepatide.
- These medications are primarily used to treat type 2 diabetes by stimulating insulin secretion, suppressing glucagon release, slowing gastric emptying, and reducing appetite.
- Typical starting doses are low with gradual increases to minimize gastrointestinal side effects like nausea and vomiting.
- GLP-1 receptor agonists offer additional benefits beyond glucose control, including weight loss and cardiovascular protection, making them valuable options for patients with type 2 diabetes, especially those with obesity or cardiovascular disease.
Administration and Dosage
- Semaglutide injections typically start at 0.25mg weekly for 4 weeks, then increase to 0.5mg weekly, with possible further increases to 1mg weekly if needed.
- These medications are administered as subcutaneous injections (except for oral semaglutide) at regular intervals ranging from twice daily to once weekly depending on the specific medication.
Cardiovascular Benefits
- The LEADER trial showed a benefit in cardiovascular outcomes with GLP-1 receptor agonists, with a 13% reduction in cardiovascular events 1.
- The SUSTAIN 6 trial confirmed the cardiovascular benefit of GLP-1 receptor agonists, with a 26% reduction in cardiovascular events 1.
Weight Loss Benefits
- Subcutaneous semaglutide was FDA approved to treat obesity in 2021 and has been shown to result in significant weight loss, with a mean weight loss of 14.9% at 68 weeks 1.
- Subcutaneous liraglutide was FDA approved to treat obesity in 2014 and has been shown to result in a mean weight loss of 8.0% at 56 weeks 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
GLP-1 Receptor Agonists
- GLP-1 receptor agonists (GLP-1 RAs) are a class of injectable glucose-lowering agents that have been developed to treat type 2 diabetes 2.
- They work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 2.
- GLP-1 RAs are available in various formulations, including twice daily (exenatide b.i.d.), once daily (lixisenatide and liraglutide), and once weekly (exenatide once weekly, dulaglutide, albiglutide, and semaglutide) 2.
- A daily oral preparation of semaglutide has also been approved, which has demonstrated clinical effectiveness close to the once-weekly subcutaneous preparation 2, 3.
Mechanisms of Action and Effects
- GLP-1 RAs have common mechanisms of action, including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, and deceleration of gastric emptying 2.
- Long-acting GLP-1 RAs have more profound effects on overnight and fasting plasma glucose and HbA1c, both on a background of oral glucose-lowering agents and in combination with basal insulin 2.
- GLP-1 RAs can also help prevent renal complications of type 2 diabetes and have been shown to reduce cardiovascular risk factors in patients with established cardiovascular disease 2, 4.
Clinical Use and Recommendations
- GLP-1 RAs are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment 2.
- They can be combined with basal insulin in either free- or fixed-dose preparations 2.
- Guidelines recommend treatment with GLP-1 RAs in patients with pre-existing atherosclerotic vascular disease, and the individual risk of ischemic or heart failure complications should guide the choice of treatment 2, 4.
- Semaglutide, a GLP-1 receptor agonist, has been shown to be safe and effective in adults and elderly patients with renal or hepatic disorders, and has been approved as a second-line treatment option for better glycemic control in type 2 diabetes 3.