The drug advertisement suggests that BoXeva should be added to metformin for the treatment of patients with type 2 diabetes mellitus. A 56-year-old woman comes to the office for follow-up. She has a history of type 2 diabetes mellitus and hypertension. The patient has been on metformin therapy for the past 6 months. Despite adhering to a diabetic diet and increasing her level of physical activity, she has been unable to lose weight. At the current visit, her blood pressure is 145/90 mm Hg, and heart rate is 72/min. Her weight is 82 kg (180 lb) . HbA_1c is 7.6%, and serum creatinine is 0.9 mg/dL.
The section of the drug advertisement shown does not mention side effects. BoXeva inhibits sodium-glucose cotransporter 2 (SGLT2) , which is expressed in the proximal renal tubules. Based on this mechanism of action, which of the following side effects would be expected for the SGLT2 inhibitor class of medications?

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Explanation: The sodium-glucose cotransporter 2 (SGLT2) promotes glucose reabsorption at the level of the proximal renal tubule. SGLT2 inhibitors can therefore reduce hyperglycemia via glucosuria. A complication frequently seen in clinical trials is vulvovaginal candidiasis (in up to 15% of women), possibly in the setting of higher urinary glucose levels. Other effects include polyuria and increased urinary tract infections. (Choices A and C) Dipeptidyl-peptidase 4 (DPP4) inhibitors should not be used in patients with a history of pancreatitis and should be discontinued in those who develop pancreatitis while on therapy. Some DPP4 inhibitors have also been associated with hypersensitivity responses, including angioedema. (Choice B) Metformin has been associated with lactic acidosis, particularly in acute renal failure. (Choice D) Flatulence and diarrhea are gastrointestinal side effects commonly seen with initiation of biguanide (eg, metformin) or α-glucosidase inhibitor (eg, acarbose) therapy. Educational objective: Sodium-glucose cotransporter 2 inhibitors reduce glucose levels by promoting renal glucose excretion and are associated with vulvovaginal candidiasis, urinary tract infections, and polyuria. References: Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor. (http://www.ncbi.nlm.nih.gov/pubmed/22632452) Canagliflozin: Improving diabetes by making urine sweet. (http://www.ncbi.nlm.nih.gov/pubmed/24186885)

The Drug Advertisement Suggests That BoXeva Should Be Added to Metformin