SGLT-2 inhibitor: The New Metformin in Type II Diabetes?

Not quite, not yet at least. But the recent 2016 interim update of the pharmacologic management of Type 2 diabetes from the Canadian Diabetes Association seems to be making a quick change in their recommendation – mainly from the results of the EMPA-REG Outcome study, a study with empagliflozin that has demonstrated  some cardiovascular and  all cause mortality benefits in very high risk patients. This is quite exciting as none of the other newer classes such as the incretin agents and the thiazolidinediones  have been able to demonstrate such superiority benefits. Only Metformin have claims in reduction of macrovascular outcomes through its UKPDS 34 trial published in 1998.

According to the interim update, metformin remains the first line agent for Type 2 diabetes. However if glycemic targets are not achieved and the patients have clinical cardiovascular disease, SGLT2 inhibtor with demonstrated CV outcome benefit is recommended.

Well at this point, it really means empagliflozin.

Empagloflozin (Jardiance®)is one of the three SGLT-2 inhibitors currently available in Canada. SGLT-2 inhibitors is the newest class of medication known as sodium glucose co-transporter inhibitors for Type 2 diabetes. They work by preventing the reabsorption of glucose in the kidney, thereby increasing the excretion of glucose and helping to lower the blood glucose.  Two other SGLT-2 inhbitors are canagliflozin (Invokana®) and dabagliflozin (Forxiga®).  Currently in Ontario, canagliflozin is covered by the Ontario Drug Benefit Program.

One of the main side effects of SGLT2 inhibitor is the increased incidence of genital and urinary tract infections.  These are quite unpleasant and in my experience, some patients eventually cannot tolerate them and went on to begin other treatment alternatives. As a class, SGLT2 inhibitors perform fairly well in terms of AIC lowering, do not cause hypoglycemia and also can contribute to weight loss and blood pressure lowering. However, they are not recommended in renal impairment. For canagliflozin and empagliflozin, they are not recommended for continued use if the CrCL drop below 45mL/min, whereas dabagliflozin is not recommended if CrCL is less than 30mL/min.

SGLT-2 inhibitors, as a class, seem to be a promising treatment option for Type 2 diabetes. However, it remains to be seen how we should best incorporate them in practice. I am awaiting results from the CANVAS and the DECLARE-TIMI58 studies which are designed to evaluate the cardiovascular benefits of canagliflozin and dabagliflozin respectively. Until then, I don’t think I can determine the final verdict of SGLT-2 inhibitors yet.

So I don’t think it is the new Metformin yet, but perhaps my view may change when new results confirm the findings in EMPA-REG Outcome study.



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My name is Cynthia Leung and I am a practicing pharmacist in Kingston Ontario, Canada. This blog is for me to share my ideas, opinions and perspectives on how medications are used in our health care system. Note that these posts are my own opinions and do not represent the opinions of my current or former employers and / or organizations that I may belong to. Any possible case scenarios described in my posts would be modified to maintain patient confidentiality. This blog is not a platform for professional advise for patients or health care providers and the content is not meant to support any clinical decisions or replace professional opinions. Also the images are either taken or created by the author, or adapted with permission. I hope you will enjoy reading my posts!

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