Easing GLP-1 Side Effects: Informed Relief for Nausea and Constipation

Executive Summary

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the treatment of type 2 diabetes and obesity and are now among the most prescribed medications for use in adults with these conditions [1].  While these medications are generally well tolerated, gastrointestinal side effects such as nausea and constipation are common and have been reported to limit therapy [2, 3].

Effective over-the-counter remedies for nausea and constipation are widely available, including Advanced Herbals® Ginger Chews for nausea, and Fleet Stimulant Oral Laxative (bisacodyl) and Fleet Liquid Glycerin Suppository for constipation. Ginger (Zingiber officinale) has a long history of use in Asian, Indian, and Arabic herbal traditions to help digestion and ease nausea [4]. The FDA has recognized laxative products to be safe and effective in the general population when used according to label instructions [5].  

Clinical investigations of strategies to reduce the incidence and severity of nausea and constipation associated with GLP-1 therapy may improve adherence and effectiveness of treatment in patients managing Type 2 diabetes and obesity.

GLP-1 Therapies: Context & Challenge

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are FDA-approved for the treatment of type 2 diabetes and obesity.  GLP-1 is a naturally occurring hormone produced in the small intestine.  GLP-1 RAs work by triggering insulin release from the pancreas; blocking the release of glucagon, a hormone that increases blood sugar; slowing digestion; and causing a sense of fullness through effects on the hunger and satiety centers in the brain.  These medications can reduce appetite and hunger, leading to significant weight loss, and may lower blood pressure, potentially reducing the risk of cardiovascular and kidney disease [1].

Although GLP-1 RAs are highly effective, side effects are common, particularly early in the course of treatment [6].  Gastrointestinal side effects occur most often, including nausea, vomiting, and constipation.  Nausea is the most frequently reported gastrointestinal symptom, occurring in 15% to 50% of treated patients.  Constipation may occur in up to 35% of patients treated for obesity, which often requires higher doses of GLP-1 therapy.  Gastrointestinal side effects may be serious enough to force patients to stop treatment, thus limiting the effectiveness of these medications [6]. 

Managing gastrointestinal side effects associated with GLP-1 therapy initially involves diet and lifestyle changes [6].  For patients with more troublesome side effects, additional strategies are often necessary to manage symptoms and permit drug continuation.  The medical literature offers limited clinical evidence on the effectiveness of specific remedies for common side effects in this patient population, although standard over-the-counter products for nausea and constipation are traditionally recommended as initial steps [6]. 

Nausea

GLP-1 medications may cause nausea through several mechanisms, including decreased emptying of the stomach and a direct central nervous system effect [7].  Treatment of GLP-1-associated nausea typically starts with dietary modification, including eating smaller portions of food, eating smaller more frequent meals, avoiding foods high in fiber and fat, and increasing fluid intake with meals [6].  In addition, certain foods may decrease the sensation of nausea, including crackers, apples, mint, ginger root, and ginger-based drinks. 

Ginger has been used for millennia to treat a variety of digestive conditions, including dyspepsia, motion sickness, and nausea associated with pregnancy and chemotherapy [8].  Ginger has been shown to potentially accelerate muscular contractions of the stomach leading to improved gastric emptying through an effect on cholinergic and serotonergic receptors [9].  This may be beneficial to patients experiencing nausea from medications that slow stomach emptying, including GLP-1 drugs.

Flavored beverages, such as ginger ale, are reportedly low in actual ginger concentration (<2% per 12 ounces) and may not be effective in this clinical setting [10].  A non-prescription alternative is Advanced Herbals® Ginger Chews, a soft chew containing 30 mg ginger extract per dose — equivalent to 500 mg ginger root per serving, a clinically tested dose of ginger for morning and motion sickness [11].  The typical dose is two ginger chews upon onset of nausea, up to twice daily. 

Constipation

GLP-1 medications decrease muscular function in the gastrointestinal tract and may lead to constipation in up to one-third of patients [6]. Typical recommendations to treat constipation in this patient population include increasing fiber in the diet, increasing physical activity, and generous hydration.  However, some of these recommendations might not be appropriate for certain patients, including diabetic patients with gastroparesis (slow stomach emptying) who may not be able to increase fiber-rich foods, and patients with significant obesity in whom physical activity is a barrier. 

A common over-the-counter choice among patients treating episodic constipation is a stool softener, such as docusate; however, stool softeners are less commonly prescribed by medical professionals due to a lack of demonstrated clinical efficacy [12].

Alternative commercially available treatments for constipation include, stimulant laxatives such as bisacodyl (Fleet® Stimulant Oral Laxative) and senna, glycerin suppositories (Fleet® Liquid Glycerin Suppositories), enemas, and osmotic laxatives such as polyethylene glycol (MiraLAX®). 

Glycerin administered rectally acts as an osmotic agent to draw water into the lower intestinal tract and can provide prompt relief of occasional constipation, usually within minutes [13].  A stimulant laxative, such as bisacodyl 5 mg orally up to three times daily, generally produces a bowel movement within 6 to 12 hours [14]. 

Conclusion

It is estimated that 12% of adults in the U.S. have taken a GLP-1 agonist, including 43% of patients with Type 2 diabetes [15].  Usage of these products is expected to increase significantly over the next five years with newer drugs and indications coming to market.  It is imperative that patients treated with GLP-1 agonists remain on their medication long term to obtain the full benefit of these drugs. 

Gastrointestinal side effects are common with GLP-1 agonists, including nausea and constipation.  Prompt therapy with widely available over-the-counter medications is an initial step in treating these side effects and potentially increasing adherence by patients taking these medications for Type 2 diabetes and obesity.
 

Appendix 1. References

  1. Nauck MA, Quast DR, Wefers J, et al. GLP-1 receptor agonists in the treatment of type 2 diabetes—State-of-the-art. Mol Metab. 2021;46:1-26.
  2. 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.
  3. Product insert: OZEMPIC (semaglutide) injection, for subcutaneous use initial U.S. approval: 2017. Available from: https://www.ozempic.com/prescribing-information.html
  4. Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: A URCC CCOP study of 576 patients. Support Care Cancer. 2012 Jul;20(7):1479–89.
  5. OTC MONOGRAPHS @ FDA. Laxative Drug Products for Over-the-Counter Human Use. Available from: https://dps.fda.gov/omuf/monographsearch
  6. Gorgojo-Martinez JJ, Mezquita-Raya P, Carretero-Gomez J, et al. Clinical recommendations to manage gastrointestinal adverse events in patients treated with GLP-1 receptor agonists: a multidisciplinary expert consensus. J Clin Med. 2023;12:145-62.
  7. Alhadeff AL, Mergler BD, Zimmer DJ, et al. Endogenous glucagon-like peptide-1 receptor signaling in the nucleus tractus solitarius is required for food intake control. Neuropsychopharmacology 2017;42:1471–79
  8. White B. Ginger: an overview. Am Fam Physician. 2007;75(11):1689-91. Available at https://www.aafp.org/pubs/afp/issues/2007/0601/p1689.pdf
  9. Giacosa A, Morazzoni P, E. Bombardelli E, et al. Can nausea and vomiting be treated with ginger extract? Eur Rev Med Pharmacol Sci. 2015:19; 1291-6.
  10. Canada Dry Ginger ale, product labeling. Canada Dry website. Available from: https://www.canadadry.com/products/ginger-ale
  11. Advanced Herbals® Ginger Chews, product labeling. Dramamine® website. Available from: https://www.dramamine.com/products/nausea-sickness-medicine/dramamine-ginger-chews
  12. Lucy AT, Massey GB, Cobbs P, et al. Successful de-implementation of an ineffective practice: The fall of docusate. Am J Surg. 2024 Feb:228:126-32.
  13. Fleet® Glycerin Suppositories, product labeling. Fleet Laboratories website. Available from: https://www.fleetlabs.com/constipation-relief-products/suppositories/fleet-glycerin-suppositories
  14. Fleet® Stimulant Oral Laxative, product labeling. Fleet Laboratories website. Available from: https://www.fleetlabs.com/constipation-relief-products/oral-laxatives/fleet-stimulant-oral-laxative
  15. Montenero A, Sparks G, Presiado M, et al. KFF Health Tracking Poll May 2024: The Public’s Use and Views of GLP-1 Drugs. Kaiser Family Foundation. Available from: https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/ Accessed June 23, 2025

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