Clinical Query

You are presented with the following case:

60 year old male patient, overweight with BMI = 28. Recently diagnosed with type 2 diabetes mellitus. He is currently taking maximum doses of metformin and sitagliptin. Generally, his blood sugar levels are not controlled, for example, his last HbA1c reading was 7.5%. He has positive family history of cardiovascular disease, his father suffered from fatal MI and the age of 52.

Would canagliflozin be a good option to reduce cardiovascular risk and what is the evidence behind this? Is it recommended for that particular patient? Any other suitable option?

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According to the CANVAS trial, it showed that canagliflozin had a 14% reduction in cardiovascular mortality in patients with T2DM. However, the study showed greater risk of amputations, mainly at the toe or foot. Canagliflozin was also shown to increase LDL and total cholesterol levels, and a greater risk for upper limb fractures. Therefore, I would not recommend canagliflozin due to the aforementioned side effects.

There is another medication in the same class called empagliflozin. According to the EMPA-REG OUTCOME, empaglifolzin has shown to reduce cardiovascular death by 38%, and all of the patients enrolled had a pre-existing cardiovascular disease, similar to your patient. Empagliflozin showed renal benefits such as reduction in progression of albuminuria. A post-hoc analysis was conducted to find any reports on amputations, but none were found. Additionally, the Canadian Diabetes Association Clinical Practice Guidelines were updated in 2016 based on the EMPA-REG OUTCOME trial because of empagliflozin’s cardiovascular benefits. Therefore, I would suggest that you consider empagliflozin for your patient.

1. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med [Internet]. 2015;373(22):2117–28. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1504720
2. Lipscombe L, Butalia S, Dasgupta K, Eurich D, Goldenberg R, Khan N, et al. Pharmacologic Management of Type 2 Diabetes : 2016 Interim Update. Can J Diabetes [Internet]. 2016;40(6):484–6. Available from: http://dx.doi.org/10.1016/j.jcjd.2016.09.003
3. Budoff MJ, Wilding JP. Effects of canagliflozin on cardiovascular risk factors in patients with type 2 diabetes mellitus. Int J Clin Pract. [Internet]. 2017;71:e12948. Available from: https://doi.org/10.1111/ijcp.12948
4. Rodriguez V, Weiss MC, Weintraub H, Goldberg IJ, Schwartzbard A. Cardiovascular disease leads to a new algorithm for diabetes treatment. Journal of Clinical Lipidology [Internet]. [Preprint]. 2017. Available from: https://doi.org/10.1016/j.jacl.2017.07.004
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