Fullscript Academy

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)

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)

Address GLP-1 agonist side effects with the evidence-based ingredients in this protocol. 

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)

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)

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)