Adjuvant therapy in glucagon-like peptide-1 receptor agonist treatment: Enhancement of efficacy and mitigation of adverse events. A review

Glucagon-like peptide-1 receptor agonists (arGLP-1) demonstrate considerable efficacy in the management of obesity and type 2 diabetes mellitus. Nonetheless, their clinical application is often restricted due to gastrointestinal adverse events, such as dyspepsia, nausea, and constipation, as well as an elevated risk of biliary sludge and gallstone disease – particularly in the context of rapid weight loss. The present review posits a multifaceted adjuvant therapy strategy that systematically modulates multiple pathophysiological pathways. At the initiation of therapy, prokinetic agents such as itopride and acotiamide are recommended to alleviate nausea and dyspepsia. Concurrently, the administration of psyllium (10–15 g/day) is recommended as a prebiotic substrate to normalize stool consistency and stimulate endogenous short-chain fatty acid synthesis. In the second stage of treatment (within 1 to 3 months), butyric acid in an enteric-coated formulation is introduced to restore intestinal barrier integrity and enhance endogenous GLP-1 secretion. Rebamipide may be used in conjunction with butyric acid to strengthen the intestinal barrier throughout the gastrointestinal tract synergistically. During the transition from the second to the third month of treatment, or when weight loss exceeds 1 kg per week, ursodeoxycholic acid (10–15 mg/kg per day) should be added. This compound is effective in preventing cholelithiasis and reducing steatosis and inflammation associated with non-alcoholic fatty liver disease. A notable advantage of the adjuvant agents discussed is their pleiotropic nature – the ability to target multiple pathophysiological mechanisms inherent to obesity and related gastroenterological conditions. Psyllium, recognized for its efficacy in managing irritable bowel syndrome, is also endorsed for the treatment of uncomplicated diverticular disease, as it normalizes intraluminal pressure and enhances colonic evacuation. Butyric acid, in addition to strengthening the intestinal barrier, offers symptomatic benefits in irritable bowel syndrome and may aid in the remission of diverticulitis by attenuating localized inflammation. Ursodeoxycholic acid, on the other hand, not only prevents cholelithiasis but also improves biochemical markers of steatosis and inflammation in non-alcoholic fatty liver disease, modifies the intestinal microbiota, and relieves symptoms associated with duodenogastric and duodenogastroesophageal reflux. The proposed therapeutic strategy aims to amplify the metabolic effects of arGLP-1 while minimizing adverse events and requires further validation through randomized controlled trials.