Patient A: Semaglutide

The mechanism of many antiobesity medications relies upon the glucagon-like peptide-1, or GLP-1, molecule, which is, in part, responsible for enhancing the secretion of insulin. Ozempic, Wegovy, and Rybelsus are the brand names of drugs with different formulations of semaglutide. Its major side effects include gastrointestinal symptoms: abdominal pain, constipation, diarrhea, nausea, and vomiting.³ It has been found to be correlated with acute kidney injury, usually prerenal in the setting of volume contraction, syncope, biliary pathology, and pancreatitis.⁴ It is believed that substantial gastrointestinal loss causes chloride and potassium depletion, as well as hypovolemia, acute kidney injury, and renal potassium loss. Patients may consequently present with vague symptoms of weakness and fatigue.

The management for this case included full labs, including a metabolic panel to assess for electrolyte abnormalities, liver function tests to assess for possible hepatic and biliary involvement, lipase to stratify risk for pancreatitis, creatine kinase to assess for potential rhabdomyolysis, urine studies, infusion of potassium chloride, analgesia and symptom control including antiemetics, and careful consideration of intravenous fluids given her hypokalemia, which represents a risk factor for over-correction of sodium and risk for osmotic demyelination. This patient’s syncope is most likely due to metabolic disruptions and fluid-status physiology; nevertheless, assessment of cardiogenic etiologies through an EKG, troponin, and cardiac risk factors should be considered as appropriate.

Similar electrolyte abnormalities can be found in refeeding syndrome, where shifts in fluids, electrolytes, and hormones may cause further deficiencies including hypophosphatemia. Patients with history of anorexia nervosa, chronic alcoholism, uncontrolled diabetes, older age, and chronic malnutrition may be at higher risk.⁴ Different agents, even with the same underlying drug, may have different formulations and effects on patients. At times, patients may also be taking other diabetes medications such as sulfonylureas or insulin, which could precipitate worsening persistent hypoglycemia. Semaglutide has a half-life of approximately one week; as such, it is long-acting and requires supportive measures. There have been documented cases of overdose, and of note, there is no known antidote.⁵ Supportive care includes dextrose infusion and consideration of reversal agents for other medications used in combination (such as glucagon for insulin and octreotide for sulfonylureas).

Patient A’s symptoms improved with intravenous fluids, antiemetics, and over-the-counter analgesia in the acute setting. Similarly to management of intractable nausea and vomiting, labs to assess for metabolic function, renal function, and acute infection should be considered. The differential should include broad infectious etiologies, electrolyte abnormalities such as those secondary to refeeding syndrome, and hyperemesis secondary to etiologies such as cannabinoid use or pregnancy. Management of symptoms is the same for all of these, relying upon fluid resuscitation, antiemetics, and electrolyte repletion. However, if a patient has such side effects of this antiobesity medication, they should discontinue taking it and follow up with their primary care physician promptly for longitudinal management of dosage and tracking of laboratory results to ensure appropriate improvement, or be admitted for this workup if there are persistent lab electrolyte abnormalities and inability to tolerate oral intake.