A Common Drug Causing a Common Side Effect at an Uncommon Time: Metformin-Induced Chronic Diarrhea and Weight Loss After Years of Treatment

Type 2 diabetes is a common condition, with a worldwide prevalence of 9.3% as of 2019 (1). Metformin is the most common drug used and is the first-line agent in type 2 diabetes management. It is also considered one of the safest pharmacological agents for the treatment of the disease. However, gastrointestinal side effects are common, occurring in up to 75% of those who take metformin (2). These side effects may include diarrhea, nausea, vomiting, abdominal discomfort, and/or flatulence, with severity ranging from mild to severe. These complications are more common with immediate-release preparations of metformin than with its extended-release formulation. Discontinuation and nonadherence rates have been as high as 46% with metformin because of these issues (3). But still, metformin remains the first choice of medication for many insulin resistance syndromes because of its effect on weight. In the Diabetes Prevention Program research study (4), metformin reduced weight by a mean 2.9 kg, and this effect persisted up to 8 years. Metformin-associated weight loss begins with initiation of the medication and is beneficial in obese individuals with or without diabetes. However, weight loss can become an unintended adverse side effect in lean individuals with type 2 diabetes. We report here a case series of patients with both adverse side effects—diarrhea and weight loss—that began after long-term use of metformin (Table 1) and provide a review of the related literature. View this table: TABLE 1 Detailed Characteristics of Patients in Cases 1–3 ### Case 1 A 63-year-old woman known to have diabetes for 17 …