Case Presentation: A 74-year-old male with a past medical history of type 2 diabetes presented with weakness, nausea, and weight loss. The patient was on metformin and glipizide at baseline, started on oral semaglutide and uptitrated to a dose of 14 mg one month prior to presentation. He reported a weight loss of 7 kg over this time due to severe anorexia, with no urine output in the days prior to admission. Patient appeared dehydrated on exam and initial labs showed a creatinine of 9.2 (baseline 1.0), BUN of 121, hypoglycemia to 51, and a serum bicarbonate of 12. He was anuric at the time. Patient received intravenous fluids, and dialysis was initiated. Patient’s uremia, hypoglycemia, and metabolic acidosis all resolved with dialysis, but he remained anorexic, without any oral intake despite encouragement. Patient was started on metoclopramide for prokinetic effect and within 2 days his appetite had returned, nausea resolved, and he was eating and drinking full meals. Kidney function improved and he was discharged without the need for dialysis.
Discussion: Glucagon-like peptide-1 (GLP-1) agonists are effective agents for the management of type 2 diabetes, obesity, and now multiple other conditions. The mechanism of action is to enhance insulin secretion in a glucose-dependent manner, suppressing glucagon release, and promoting satiety–leading to improved glycemic control and weight loss. Furthermore, it slows gastric emptying and decreases food intake. Gastrointestinal side effects are common, with decreased appetite a desired outcome in patients for whom weight loss is the prescribed condition, with gastroparesis and anorexia on the severe end of the spectrum. The dose-dependent relationship is consistent with this presentation, as the patient developed symptoms after an increase in dosage.Literature on the management of GLP-1 agonist induced side effects is nascent and this case highlights successful management and treatment of GLP-1 induced anorexia with metoclopramide. Metoclopramide functions as both an antiemetic and pro-kinetic agent. It works primarily as an anti-emetic by antagonizing dopamine receptors both centrally and peripherally by decreasing the sensitivity of visceral afferent nerves to the area postrema, the vomiting center of the brain. It is also a prokinetic agent that functionsprimarily at the upper GI tract. It increases the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum, resulting in accelerated gastric emptying and intestinal transit. These physiologic mechanisms are most likely responsible for the usefulness in the management of GLP-1 agonist induced anorexia. In this case, the patient’s rapid improvement was likely due to the prokinetic agent countering the severely reduced gut motility. Metoclopramide should be considered in the armamentarium to manage GLP-1 agonist induced anorexia.
Conclusions: GLP-1 agonists are increasingly used for diabetes, obesity, and beyond. Gastrointestinal side effects are common, although severe anorexia as above is atypical. When anorexia is severe enough to cause downstream consequences beyond intention, prokinetic agents can be helpful to mitigate. This case demonstrates the potential utility of metoclopramide in treatment of GLP-1 agonist induced anorexia. As these medications are continuing to rise in their popularity and clinical usefulness, mitigation of side effects will become more important.