Adverse Events Due to Oral Hypoglycemic Drugs

The management of type 2 diabetes mellitus (T2DM) demands careful consideration of patient characteristics, disease severity, and therapeutic options, with a focus on addressing the “ominous octet” of pathophysiological mechanisms contributing to hyperglycemia. This chapter provides an extensive review of the adverse effects associated with various oral hypoglycemic drugs commonly used in T2DM treatment. Specifically, the adverse effects of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, alpha-glucosidase inhibitors (AGIs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors are examined in detail. For metformin, gastrointestinal intolerance, lactic acidosis, and vitamin B12 deficiency are the key adverse effects that must be monitored, particularly in elderly patients. SUs are associated with a high risk of hypoglycemia, weight gain, skin rashes, and concerns regarding cardiovascular outcomes, especially with glibenclamide. Similarly, TZDs have been linked to cardiovascular risks, bone fractures, fluid retention, heart failure, and an increased risk of bladder cancer, necessitating careful patient selection. DPP-4 inhibitors exhibit generally favorable tolerability, but concerns about pancreatitis, heart failure, joint pain, and bullous pemphigoid require attention. GLP-1 receptor agonists, while effective in managing T2DM, can lead to gastrointestinal effects, acute pancreatitis, and an immunogenic response, demanding careful monitoring. Alpha-glucosidase inhibitors are associated with gastrointestinal side effects and occasional reports of paralytic ileus and liver transaminase elevation. SGLT2 inhibitors may lead to genital and urinary tract infections, euglycemic ketoacidosis, acute kidney injury, dehydration, and hypotension, necessitating cautious prescribing and vigilant monitoring. Considering the intricacies of adverse effects, the chapter emphasizes the importance of tailoring treatment to individual patient needs, incorporating open discussions to align therapy with patient preferences while minimizing potential risks. Ongoing monitoring and evaluation are crucial to optimizing glycemic control and minimizing adverse effects throughout the course of treatment.