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GLP-1 Agonist Side Effect Support



Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which is a peptide produced in the gut as a response to a meal. Once produced, it binds to the receptors on the pancreas, stimulating insulin secretion and potentially decreasing blood glucose levels. (Müller, 2019)  GLP-1 is also considered a neuropeptide, which can activate receptors in the brain to delay gastric emptying and promote satiety. (Kim 2021)

Due to the influence of GLP-1 on the body, GLP-1 agonist medications were developed and utilized to treat type 2 diabetes. (Sodhi 2023)  However, since GLP-1 can reduce gastric motility and support satiety, possibly decreasing food intake, hunger, and appetite, it’s now also used to support weight loss. (Cleveland Clinic 2023) There are several examples of GLP-1 agonists, which vary in administration and duration of action, including semaglutide, dulaglutide, exenatide, liraglutide, and lixisenatide. (FDA 2024)

For individuals taking GLP-1 agonists, dietary supplements may be recommended to help prevent or address the adverse effects of these types of medication. The most commonly reported are gastrointestinal (GI) related, such as nausea, vomiting, or diarrhea. (Cleveland Clinic 2023)  Moreover, preserving muscle mass and meeting nutrient requirements is important when reducing weight through decreased food intake. 

This protocol is intended to support the use of GLP-1 agonists by helping to alleviate potential side effects and support healthy weight management. There’s little data available to highlight adjunctive or concomitant effects with GLP-agonist medications directly; as a result, the evidence supporting the use of certain ingredients is based on the mechanisms that may support the specific side effects and general weight management goals.


Ginger

500 mg, twice daily, or 1–2 g daily, depending on frequency and timing of nausea onset; if nausea occurs after injection, taking 1 hour prior to administration may be helpful Chaiyakunapruk 2006)

  • A meta-analysis of the use of ginger for postoperative nausea, a symptom that’s generally induced by medication (anesthetic), concluded that ginger effectively prevented nausea for a 24-hour period.(Chaiyakunapruk 2006)

  • Another meta-analysis reviewing medication-induced nausea and vomiting from chemotherapy found that ginger was able to reduce acute episodes of nausea and vomiting by 40%. (Chang 2019)

  • A randomized clinical trial evaluating ginger for preventing nausea and vomiting from antiviral medication found that only 39% of participants experienced nausea and vomiting in the ginger group compared to 60% in the placebo group. (Dabagzadeh 2014)


Probiotics

60 billion CFU of Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07, as tolerated until GI discomfort resolves completely

  • In a double-blind, randomized, placebo-controlled (DBRPC) trial using a combination of  L. acidophilus NCFM and B. lactis Bi-07, both probiotics were found to improve distention and bloating by 15%. (Ringel-Kulka 2011) 

  •  L. acidophilus NCFM alone has been found to modulate pain-associated receptors in the GI tract of humans, potentially reducing abdominal pain. (Zhang 2022)

  • A large RCT evaluating L. acidophilus NCFM and B. lactis Bi-07 and BI-04 strains found that supplementation with these probiotics strains reduced diarrhea and bloating by more than 50% and abdominal pain by more than 80%. (Ouwehand 2014)


Protein

24 g of protein, 1–2 times daily, ongoing, until support is no longer needed

  • During a weight loss regimen, it is important to support muscle mass, so weight loss comes from fat mass instead of muscle. (Leidy 2015)

  • A systematic review and meta-analysis compared the effects of protein supplementation on body composition in individuals with overweight or obesity to a placebo or controls. The study confirmed that whey protein can significantly reduce body weight and fat mass. (Wirunsawanya 2018)

  • Another systematic review and meta-analysis concluded that whey protein can increase lean mass without influencing fat mass, and these effects were more prominent when an energy-restricted component was included. (Bergia 2018)


Creatine

3–5 g daily as creatine monohydrate, ongoing (Kreider 2017)

  • In a meta-analysis reviewing the evidence of creatine and fat mass, the authors concluded that adults supplementing with creatine lost 0.5 kg more fat mass compared to those taking a placebo during resistance training. (Forbes 2019)

  • A combined systematic review and meta-analysis found that during anaerobic or aerobic exercise, creatine had a significant effect on metabolic outcomes, including increased muscle mass and decreased fat mass, in both groups compared to a placebo. (Jaramillo 2023)

  • Compared to other forms of creatine, creatine monohydrate has the most evidence by far to support its effectiveness in providing muscle support during exercise. It has also been shown to be safe and economical. (Fazio 2022)


Multivitamin

Multivitamin formulation, daily, ongoing 

  • A review of popular low-carb/high-protein (e.g., Atkins) or heart-healthy (e.g., DASH diet) diet plans found that to meet 100% of the RDI of 27 micronutrients, a caloric intake would need to be >18,000 kcal per day, consistently (Calton 2010). As a result, it would be unrealistic to reach the RDI on these diets, so supplementation would be necessary. 

  • A 2020 review of the micronutrient status of patients with obesity found that the most common deficiencies in this population tend to be carotenoids, manganese, magnesium, chromium, vanadium, and vitamins A, D, B1, B9, and B12. (Lapik 2020)

  • An RDBPC trial of individuals on diets that didn’t meet the Recommended Dietary Allowance (RDA) who took a multivitamin and mineral supplement (MVM) found that supplementation improved blood concentrations of pyridoxal phosphate, calcifediol, α-tocopherol, and β-carotene concentrations by 30% overall, while the placebo group showed declines in blood vitamin concentrations and an increased prevalence of suboptimal vitamin status during the six-month trial. However, the MVM did not significantly affect mineral concentrations. (Michels 2023)


Evidence rating

The following protocols were developed using only a,b,c-quality evidence

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References
  1. Müller, T. D., et al. “Glucagon-like Peptide 1 (GLP-1).” Molecular Metabolism, vol. 30, 2019, pp. 72-130, https://doi.org/10.1016/j.molmet.2019.09.010. Accessed 26 Feb. 2024.

  2. Sodhi M, et al. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. 2023;330(18):1795–1797. doi:10.1001/jama.2023.19574

  3. US Food and Drug Administration. Medication containing semaglutide marketed for type 2 diabetes or weight loss. 2024.  

  4. Cleveland Clinic. GLP-1 Agonist. 2023. 

  5. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C. The efficacy of ginger for preventing postoperative nausea and vomiting: a meta-analysis. Am J Obstet Gynecol. 2006;194(1):95-99. doi:10.1016/j.ajog.2005.06.046

  6. Mandal P, Das A, Majumdar S, Bhattacharyya T, Mitra T, Kundu R. The efficacy of ginger added to ondansetron for preventing postoperative nausea and vomiting in ambulatory surgery. Pharmacognosy Res. 2014;6(1):52-57. doi:10.4103/0974-8490.122918

  7. Dabaghzadeh F, Khalili H, Dashti-Khavidaki S, Abbasian L, Moeinifard A. Ginger for prevention of antiretroviral-induced nausea and vomiting: a randomized clinical trial. Expert Opin Drug Saf. 2014;13(7):859-866. doi:10.1517/14740338.2014.914170

  8. Ringel-Kulka T, Palsson OS, Maier D, et al. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol. 2011;45(6):518-525. doi:10.1097/MCG.0b013e31820ca4d6

  9. Zhang, Tao, et al. “Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.” Frontiers in Cellular and Infection Microbiology, vol. 12, 2022, p. 859967, https://doi.org/10.3389/fcimb.2022.859967. Accessed 6 Mar. 2024

  10. Ouwehand AC, DongLian C, Weijian X, et al. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose-response study. Vaccine. 2014;32(4):458-463. doi:10.1016/j.vaccine.2013.11.053

  11. Wirunsawanya K, et al. Whey Protein Supplementation Improves Body Composition and Cardiovascular Risk Factors in Overweight and Obese Patients: A Systematic Review and Meta-Analysis. J Am Coll Nutr. 2018;37(1):60-70. doi:10.1080/07315724.2017.1344591

  12. Bergia, R. E., 3rd, Hudson, J. L., & Campbell, W. W. (2018). Effect of whey protein supplementation on body composition changes in women: a systematic review and meta-analysis. Nutrition Reviews, 76(7), 539–551. https://doi.org/10.1093/nutrit/nuy017

  13. Kim JY. Optimal Diet Strategies for Weight Loss and Weight Loss Maintenance. J Obes Metab Syndr. 2021;30(1):20-31. doi:10.7570/jomes20065

  14. Forbes SC, Candow DG, Krentz JR, Roberts MD, Young KC. Changes in Fat Mass Following Creatine Supplementation and Resistance Training in Adults ≥50 Years of Age: A Meta-Analysis. J Funct Morphol Kinesiol. 2019;4(3):62. Published 2019 Aug 23. doi:10.3390/jfmk4030062.

  15. Jaramillo AP, Jaramillo L, Castells J, et al. Effectiveness of Creatine in Metabolic Performance: A Systematic Review and Meta-Analysis. Cureus. 2023;15(9):e45282. Published 2023 Sep 15. doi:10.7759/cureus.45282

  16. Fazio C, Elder CL, Harris MM. Efficacy of Alternative Forms of Creatine Supplementation on Improving Performance and Body Composition in Healthy Subjects: A Systematic Review. J Strength Cond Res. 2022;36(9):2663-2670. doi:10.1519/JSC.0000000000003873

  17. Michels AJ, Butler JA, Uesugi SL, et al. Multivitamin/Multimineral Supplementation Prevents or Reverses Decline in Vitamin Biomarkers and Cellular Energy Metabolism in Healthy Older Men: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2023;15(12):2691. Published 2023 Jun 9. doi:10.3390/nu15122691

Disclaimer: Protocols are intended solely as an informational reference tool for practicing health care professionals. The content provided is not intended to be for medical diagnosis or treatment, is not a substitute for your professional judgment, and is not meant to provide you medical or professional advice. You should evaluate and independently confirm the appropriateness of the content provided, including verifying uses, dosages, warnings and contraindications on product labels, and rely on your experience and judgment and other available resources when applying the provided content to an actual patient care situation. While content has been obtained from sources believed to be reliable, we cannot and do not guarantee the accuracy, validity, timeliness or completeness of the content. We make no representation or warranty, express or implied, including, without limitation, any warranty of merchantability or of fitness for a particular purpose, and you assume full responsibility for the use of the content and products, and agree that Fullscript and its content providers are not responsible or liable for any claim, loss, injury or damage arising from your use of the information. Statements regarding dietary and other health care supplements have not been evaluated by the FDA, and are not intended to diagnose, treat, cure, or prevent any disease.


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