For HCPs: Gastrointestinal Side Effects Associated with GLP-1 Therapy: Focus on Nausea and Constipation
Glucagon-like peptide-1 receptor agonists (GLP-1s) are approved for use in the management of type 2 diabetes and obesity. As an increasing number of patients are prescribed GLP-1s, the gastrointestinal (GI) side effects associated with GLP-1 therapy are becoming an important consideration in patient management. Nausea and constipation are among the most commonly reported GI side effects particularly during treatment initiation and dose escalation. 1,2
These GI side effects are generally most pronounced during early phases of therapy and are thought to be related to delayed gastric emptying and central appetite regulation mechanisms associated with GLP-1s.3 The severity and duration of symptoms varies among patients and are reported to decrease over time with continued therapy. However, some patients may experience symptoms so severe or persistent they hamper their GLP-1 journey and require changes to their ideal treatment regimen 1, 4, 5, 6
From a clinical practice perspective, counseling prior to initiation of therapy helps to establish expectations regarding the potential for GLP-1 side effects. Patient education regarding GLP-1 side effect symptoms, timing, variability, and the possibility of treatment adjustment will support shared decision-making and encourage patient engagement. Additional strategies commonly utilized in practice include recommendations for dietary modifications, hydration guidance, encouragement of patient communication during dose escalation, and physician’s reinforcement of these supportive strategies.
REFERENCES
1. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
2. Pi-Sunyer X, Astrup A, Fjioka K, et al. A Randomized Trial of Liraglutide for Weight Management. N Engl J Med. 2015;373:11–22. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa1411892
3. Blundell J, Finlayson G, Axelsen M, et al. Mechanisms of GLP-1 receptor agonists on appetite regulation and gastric emptying. Diabetes Obes Metab. 2017. Sep;19(9):1242-1251. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5573908/.
4. Husain M, Birkenfeld AL, Donsmark M, et al. GLP-1s and cardiovascular outcomes in patients with Type 2 diabetes. N Engl J Med. 2019;381:841-51.
5. Product insert: OZEMPIC (semaglutide) injection, for subcutaneous use initial U.S. approval: 2017. Available from: https://www.ozempic.com/prescribing-information.html
6. Filippatos TD, Panagiotopoulou TV, Elisaf MS. Adverse effects of GLP-1 receptor agonists. Rev Diabet Stud. 2015 Feb 10;11(3):202–230. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5397288/#sec19