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Stop Using Sulfonylureas?

The ACP has issued a clinical practice guideline regarding use of oral agents in type 2 diabetes entitled, “Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians.”…

This is important because despite new therapies, there hasn’t been a guideline from either the ADA or AACE in a while. Of note, the more recent AACE/ACE guideline from a few years ago says that metformin is probably best, but you can start with whatever you want, except for sulfonylurea. The actual ADA guideline says start with metformin and then add either SU, TZD or insulin. A consensus statement (not guideline) from the author of the ADA guideline changed things to start with metformin and then add SU or insulin.

See more SGLT-2 Resources

The ACP guideline first reviewed all the literature comparing different diabetes agents alone or in combination and looked at outcomes beyond A1c reduction. This is known as comparative effectiveness, and we should expect to see a lot more of this in the US, although the UK has been doing this for some time.

A summary of the ACP’s three recommendations are as follows:

  • Recommendation 1: Use medications in patients diagnosed with type 2 diabetes when lifestyle modifications aren’t working
  • Recommendation 2: Start with metformin in most patients with type 2
  • Recommendation 3: Add a second agent when metformin alone is not enough.

This is all based on high quality evidence. Unfortunately the evidence comparing agents other than metformin was less than robust, and they could not really recommend one agent over another. This suggests that physicians, after starting on metformin, can choose a second agent based on properties of those specific agents that may be beneficial to a particular patient (i.e. GLP-1 analogues for overweight patients), avoid agents with unwanted side effects (i.e. not using TZD’s in patients with fluid overload) as well as other factors such as cost and patient preference.

Though the recommendations don’t clarify much other than to start with metformin, statements in the discussion section do clarify one thing:

According to the ACP, “The evidence shows that most diabetes medications reduced HbA1c levels to a similar degree. Metformin was more effective than other medications as monotherapy as well as when used in combination therapy.” “High-quality evidence shows that the risk for hypoglycemia with sulfonylureas exceeds the risk with metformin or thiazolidinediones.”

In other words, though not exactly stated as a major recommendation, it appears that physicians should start with metformin, then add something else (TZD, DPP4, GLP-1, SGLT-2 -when available), but probably not sulfonylurea, since it clearly causes more hypoglycemia than anything else.

SU’s are effective, but not good medications. They cause significant hypoglycemia. They cause weight gain. They “burn out” the pancreas. All of the others do not cause hypoglycemia. All except for TZD’s are weight neutral or cause weight loss. All the other appear to preserve beta cell function. The only reason to use SU’s in 2012 is due to cost. However, in the US most of the branded combination pills come with a coupon card that would take the cost to the same as adding an SU. Kombiglyze XR (DPP4+ Met) is once a day and has a coupon card that takes the out of pocket cost down to $10. Janumet XR has a $5 coupon card.

Given all the evidence, plus practical ways for patients to reduce the costs of branded diabetes medications, is there any reason to use sulfonylureas as anything more than a 3rd or 4th line agent?

American College of Physicians, Feb 2012

You can click HERE for the full text PDF (which is free-thanks ACP!)