From the Guidelines
Semaglutide is the safest GLP-1 receptor agonist due to its extensive clinical experience and robust safety data, as demonstrated in the SUSTAIN-6 trial 1. When considering the safety of GLP-1 receptor agonists, it's essential to evaluate their potential to reduce cardiovascular risk and minimize adverse events. The SUSTAIN-6 trial, which compared semaglutide to placebo, found that semaglutide reduced the risk of cardiovascular death, nonfatal MI, or nonfatal stroke by 26% (HR 0.74; 95% CI 0.58–0.95; P < 0.001) 1. Key points to consider when evaluating the safety of GLP-1 receptor agonists include:
- Their ability to reduce cardiovascular risk, as seen in the SUSTAIN-6 trial with semaglutide 1
- Their potential to cause gastrointestinal side effects, such as nausea, vomiting, and diarrhea, which are common among all GLP-1 receptor agonists
- The importance of starting at low doses and gradually increasing to minimize gastrointestinal side effects, as recommended for semaglutide (starting at 0.25mg weekly for 4 weeks, then 0.5mg weekly, potentially increasing to 1mg weekly if needed)
- The need to avoid GLP-1 medications in individuals with a personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 Overall, semaglutide's safety profile, combined with its established efficacy in reducing cardiovascular risk, makes it a preferred choice among GLP-1 receptor agonists.
From the Research
Safety of GLP-1 Receptor Agonists
The safety of GLP-1 receptor agonists has been evaluated in several studies. Key findings include:
- Liraglutide, a GLP-1 receptor agonist, has been associated with a lower risk of hypoglycemia compared to certain other classes of antidiabetic agents 2, 3.
- GLP-1 receptor agonists, including liraglutide, have been found to promote weight loss and improve patient satisfaction and health-related quality of life 2, 3.
- The risk of pancreatitis and pancreatic cancer with GLP-1 receptor agonists has been evaluated in several meta-analyses, with no clear evidence of increased risk found 4.
Comparison of GLP-1 Receptor Agonists
Several head-to-head trials have compared the safety and efficacy of different GLP-1 receptor agonists, including:
- Dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and oral semaglutide have been found to be effective therapeutic options for reducing A1C, although differences exist in terms of magnitude of effect and frequency of adverse effects 5.
- Long-acting GLP-1 receptor agonists, including both injectable and oral formulations, have been found to reduce the incidence of major adverse cardiovascular events, hospitalization for heart failure, and kidney events, as well as all-cause mortality 6.
Adverse Effects
Common adverse effects of GLP-1 receptor agonists include: