MKSAP quiz: Adverse medication effects
This month's quiz asks readers to evaluate a man with type 2 diabetes who is taking glipizide and empagliflozin and has nausea, vomiting, and fatigue.
A 66-year-old man recently diagnosed with type 2 diabetes mellitus is evaluated in the emergency department for nausea, vomiting, and fatigue. He was diagnosed with type 2 diabetes 18 months ago. In the past month metformin was discontinued due to severe diarrhea, and glipizide and empagliflozin were initiated. In addition to type 2 diabetes, medical history is significant for coronary artery disease, hypertension, and dyslipidemia. Medications are aspirin, lisinopril, metoprolol, atorvastatin, glipizide, and empagliflozin.
On physical examination, temperature is normal, blood pressure is 90/60 mm Hg, pulse rate is 120/min, and respiration rate is 22/min. Dry mucous membranes are noted. There is diffuse abdominal tenderness to palpation without guarding. Other than tachycardia, the remainder of the examination is normal.
Laboratory studies show sodium 133 mEq/L (133 mmol/L), bicarbonate 10 mEq/L (10 mmol/L), glucose 150 mg/dL (8.3 mmol/L), anion gap 17 mEq/L (17 mmol/L), and elevated β-hydroxybutyrate.
Which of the following is most likely responsible for the patient's findings?
A. Atorvastatin
B. Discontinuation of metformin
C. Empagliflozin
D. Glipizide
E. Lisinopril
MKSAP Answer and Critique
The correct answer is C. Empagliflozin. This item is available to MKSAP 18 subscribers as item 72 in the Endocrinology and Metabolism section. More information about MKSAP 18 is available online.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors (canagliflozin, dapagliflozin, and empagliflozin) improve glycemia by increasing excretion of glucose by the kidney. SGLT2 is expressed in the proximal tubule and mediates reabsorption of approximately 90% of the filtered glucose load. SGLT2 inhibitors promote excretion of glucose by the kidneys and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes. Euglycemic diabetic ketoacidosis has been reported in patients with type 2 diabetes taking SGLT2 inhibitors. Because of this, the FDA issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis with uncharacteristically mild to moderate glucose elevations (euglycemic diabetic ketoacidosis) associated with the use of all the approved SGLT2 inhibitors. SGLT2 inhibitors should be discontinued in patients who develop acidosis on these agents.
Statins may cause myopathy and liver aminotransferase elevations and are associated with an increased risk of diabetes and, possibly, cognitive dysfunction. The incidence of these adverse effects ranges from 1% to 10%, but permanent disability related to statin intolerance is rare. Statin therapy is not associated with ketoacidosis.
According to labeling guidelines, initiation of metformin therapy is not recommended if the estimated glomerular filtration rate (eGFR) is between 30 and 45 mL/min/1.73 m2 and is contraindicated if the eGFR is less than 30 mL/min/1.73 m2 due to the risk of lactic acidosis. Metformin should be used cautiously in patients with heart failure or hepatic impairment. The discontinuation of metformin is not associated with the development of lactic acidosis or ketoacidosis.
Glipizide is a sulfonylurea. Sulfonylurea agents work by stimulating insulin secretion. Sulfonylurea agents are associated with weight gain, and they can cause hypoglycemia. They are not, however, associated with the development of ketoacidosis in patients with type 2 diabetes.
A common adverse effect of ACE inhibitors is a dry, nonproductive cough. Other common adverse effects include hyperkalemia and, occasionally, worsening kidney function. ACE inhibitors can cause life-threatening angioedema but not ketoacidosis.
Key Point
- An increased risk of diabetic ketoacidosis with mild to moderate glucose elevations has been associated with the use of all the approved sodium-glucose transporter-2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin).