Exocrine Pancreatic Insufficiency During the Use of Semaglutide: A Case Report

Although acute pancreatitis has been reported as an adverse event in patients treated with glucagon-like peptide-1 (GLP-1) analogues, to date we have not identified a case describing exocrine pancreatic insufficiency related to this drug. Here we present a case of a patient with no history of acute pancreatitis, who was diagnosed with exocrine pancreatic insufficiency during the third year of weekly subcutaneous semaglutide for obesity control. A 68-year-old man with previous unsuccessful therapeutic approaches for weight loss used subcutaneous semaglutide, once a week, for 181 weeks. The pharmacological treatment, combined with instructions on lifestyle changes, resulted in a weight loss of 11.6% of initial body weight, with a reduction in body mass index from 35.7 to 31.9 kg/m2. The patient received a regular dose of 0.5mg/week in the first 14 weeks in a private physician's office. During this period, an asymptomatic elevation of serum lipase was identified and attributed to alcohol consumption. Because the patient complained of less satiety and weight loss stabilization, the dose of semaglutide was increased to 1.0mg/week. Serum lipase levels increased to up to eight times the upper normal limit and the use of semaglutide was discontinued for 10 weeks. Due to progressive weight regain and serum lipase levels being near normal, semaglutide was reintroduced at 0.25mg/week with progressive increments until 1.0mg/week. The patient missed the follow-up appointments, continued the same dose of semaglutide for another 16 weeks, and discontinued treatment after another asymptomatic elevation in serum lipase levels. Four weeks later, the patient reported steatorrhea and was seen by a gastroenterologist, who diagnosed exocrine pancreatic insufficiency. The course of our case suggests a potential association between semaglutide and chronic alcohol consumption in the development of exogenous pancreatic insufficiency. We call attention to the importance of regular monitoring of serum lipase levels in patients taking GLP-1 analogues and suggest that the consumption of any amount of alcohol should be discouraged in patients in long-term treatment with glucagon-like peptide-1 receptor agonists.