The Eternal Question: What Comes after Metformin?

Republicans and Democrats, Red Sox and Yankee fans, all agree on one thing: metformin is the drug of choice for initial treatment of type 2 diabetes. But if metformin monotherapy does not achieve glycemic control, what comes next?

The next issue of The Medical Letter includes an article on dapagliflozin (Farxiga), a new oral drug for type 2 diabetes, and the next issue of Treatment Guidelines from The Medical Letter will be on Drugs for Diabetes. These 2 publications may not settle for all time what to use after metformin, but they should provide some excellent background for making an informed choice. I can give you a small preview.

Dapagliflozin is an SGLT2 inhibitor. It is the second SGLT2 inhibitor to reach the US market; canagliflozin (Invokana), which we reviewed in the May 13, 2013 issue of The Medical Letter, was the first. SGLT-2 inhibitors do not affect insulin production or sensitivity. Rather, they decrease renal glucose reabsorption and increase urinary glucose excretion, resulting in a reduction in blood glucose levels. SGLT2 inhibitors have some attractive characteristics: they are oral, they do not cause hypoglycemia, and they do not cause weight gain. Actually, they seem to cause a modest loss of weight. And their HbA1c-lowering effect is not bad. But they have some side effects, and their long-term safety is still a concern.

Our article on Drugs for Diabetes will take you through the pros and cons of the various candidates vying to be the drug of choice for addition to metformin. There will be the sulfonylureas, tried and true, and for only $4/month, maybe we can accept a little hypoglycemia and weight gain. And there will be the thiazolidinedione rosiglitazone (Avandia), recently released from bondage by the FDA (see Rosiglitazone Unbound in the February 3, 2014 issue of The Medical Letter). And incretin-based therapy: the DPP-4 inhibitors and the GLP-1 receptor agonists. They will all be there, and we may even go out on a strong-looking limb and suggest a choice among them. Watch for it.

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  1. Hervy Md says:

    I like the four dollar pill!

  2. Kevin Schaller says:

    Another drug with unknown benefits for micro or maculvascular outcomes, and safety concerns? Do we really need another one of those?

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