A 56-year-old woman comes to the physician for follow-up of uncontrolled type 2 diabetes mellitus. Her other medical problems include hypertension and hyperlipidemia. Despite optimal lifestyle and compliance with medications, her fasting blood glucose levels on home glucose monitoring range from 140-160 mg/dL. Her last hemoglobin A_1c performed 4 weeks ago was 8.2%. Her current medications include metformin, sitagliptin, amlodipine, hydrochlorothiazide, and simvastatin.
Blood pressure is 102/70 mm Hg, pulse is 89/min, and BMI is 34 kg/m². The rest of the physical examination is unremarkable.
The patient does not want to go on insulin or any other injectable medications. Adding canagliflozin to her current anti-diabetic medication is considered.
Which of the following medications will most likely need dose adjustment or discontinuation if canagliflozin is added?

Question

Quizplus · Accepted Answer

11ec193a_97ab_0da3_853d_b5d09ec98e95_MD0002_00 Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that works by decreasing the tubular reabsorption of glucose. The kidneys filter approximately 180 g of glucose each day and almost all of the filtered glucose is reabsorbed, mainly by SGLT2 in the proximal tubules. In type 2 diabetes mellitus, inhibition of SGLT2 reduces reabsorption of filtered glucose and improves glycemic control. In clinical trials, the average reduction in hemoglobin A_1c with SGLT2 inhibitors is approximately 0.5%-1%. _1c The adverse effects of SGLT2 inhibitors are mainly due to excessive loss of sodium and glucose in the urine. Glucosuria can increase the risk of genital candidiasis and urinary tract infections. SGLT2 inhibitors also induce an osmotic diuresis, which can lead to hypotension and decreased renal perfusion. Elderly patients and those taking diuretics or drugs which affect the renin-angiotensin-aldosterone system (eg, ACE inhibitors, angiotensin receptor blockers) are at greatest risk. This patient is on a diuretic and is already hypotensive and should have her thiazide dose decreased or discontinued prior to initiating canagliflozin. (Choice A) Amlodipine has no direct interaction with canagliflozin and likely may be continued. However, this patient's blood pressure should be monitored closely, and amlodipine may also need to be decreased or discontinued depending on her clinical course. (Choices C and E) Hypoglycemia is uncommon with SGLT2 inhibitors in combination with metformin and/or sitagliptin; these medications do not generally require dose adjustment. Hypoglycemia is more common when SGLT2 inhibitors are used in combination with insulin or insulin secretagogues (eg, sulfonylureas). (Choice D) There is no significant interaction between simvastatin and SGLT2 inhibitors. Educational objective: SGLT2 inhibitors lower blood glucose by decreasing the reabsorption of glucose in the kidney. The most common side effects are genital candidiasis, urinary tract infections, and osmotic diuresis leading to hypotension. __________ References: Place of sodium-glucose co-transporter type 2 inhibitors for treatment of type 2 diabetes. (http://www.ncbi.nlm.nih.gov/pubmed/25512787)

A 56-Year-Old Woman Comes to the Physician for Follow-Up of Uncontrolled