Bradley M. Wright, MD

John Wilson is 76 years old and comes to your clinic for a follow-up of type 2 diabetes mellitus (T2DM). His past medical history also includes hypertension and depression. T2DM was diagnosed 10 years ago, and John has been well controlled on metformin and diet. His hemoglobin A1c (A1c) at his visit 1 year ago was 6.8%. He lives alone, is retired, and is proud to say that he still walks 2 miles every day. His current medications are metformin 1000 mg twice daily, lisinopril 10 mg daily, and fluoxetine 40 mg daily. Results of his most recent laboratory studies include A1c, 7.6%; basic metabolic panel, WNL (SCr 0.8 mg/dL, eGFR, 70 mL/min). Vitals signs are 83 kg (5 kg increase over the past year); blood pressure, 136/82 mm Hg; pulse, 74 beats/min.

It is clear that another agent should be added to John’s regimen and you discuss options with him. You agree that an agent that would not cause weight gain and would even promote weight loss would be preferred. Adding a glucagon-like peptide-1 agonist would be an appropriate step but even after you show him a sample of an injection pen he refuses to “get involved with any needle business.” You have another patient a few years younger than John but at a similar stage of diabetes progression. He has been taking a sodium-glucose cotransporter 2 (SGLT2) inhibitor for the past several months and is tolerating it quite well.

Can the SGLT2 inhibitor canagliflozin be used as add-on therapy in this elderly patient with uncontrolled T2DM?

 Yes, canagliflozin is safe and effective in elderly patients.

 No, canagliflozin is significantly less effective in elderly patients.

 Yes, but canagliflozin dose should not exceed 100 mg per day because of safety concerns in elderly patients.

 No, canagliflozin is associated with significantly higher percentage of adverse effects in patients older than 65 years and so is not safe in elderly patients

No, canagliflozin cannot be combined with metformin therapy in elderly patients.

Answer: A. Yes, canagliflozin is safe and effective in elderly patients

The sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin represents a new class of oral antihyperglycemic agents that increase the urinary excretion of glucose in patients with hyperglycemia. This effect results in lower blood glucose levels as well as mild diuresis that can result in weight loss and lower blood pressure. A phase 3 study of canagliflozin 100 mg daily and 300 mg daily in patients aged 55 to 80 years showed significant decreases in A1c and fasting blood glucose.

Results of the phase 3 study of canagliflozin in patients aged 55 to 80 years make 

 Further, a pooled analysis of 4 randomized controlled phase 3 clinical trials also showed that both doses of canagliflozin were effective in patients older than 65 years. In addition, while A1c reductions were slightly numerically lower, the overall reduction in A1c was similar in patients younger than 65 years and those older than 65 years.

Product labeling for canagliflozin indicates a maximum dose of 100 mg daily for patients with moderate renal impairment

; there are no maximum dose recommendations based on age, so 

. This patient has no significant renal impairment and can therefore be titrated to the 300-mg daily dose.

. In the pooled analysis comparing patients younger than 65 years with those older than 65 years,

 no significant increase in adverse drug reactions was identified in the group of patients older than 65 years. While adverse events such as urinary tract and genital mycotic infections are associated with SGLT2 inhibitor use and would be of concern in this population, no increase in these adverse effects was observed in trial patients  older than 65 years when compared with those younger than 65 years. Canagliflozin can be used safely in the elderly population with close monitoring for these adverse events.  

Canagliflozin has been studied in combination with other antihyperglycemic agents, including metformin, and has been found to be safe and effective when used in combination with metformin.

Sinclair A, Bode B, Harris S, et al. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021426.

Bode B, Stenlof K, Sullivan D, et al. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial. 

http://www.ncbi.nlm.nih.gov/pubmed/?term=BMC+Hosp+Pract.+2013%3B+41%29%3A72-84

INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2014. 

http://www.invokanahcp.com/prescribing-information.pdf

Articles

John is an active older man whose A1c has gone from 6.8% to 7.6% since his last follow-up visit. He refuses to get involved in any “needle business.” What’s next? 

Bradley M. Wright, MD

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Type 2 Diabetes in a 76-Year-Old Man: Which Drug to Add On?