Diabetes Drugs

On July 23, 2012, The Medical Letter published an article titled “What Comes after Metformin for Type 2 Diabetes?” It concluded, in part:

      When metformin does not adequately control hyperglycemia, addition of a sulfonylurea appears to offer the best combination of effectiveness, low cost and convenience, but weight gain and hypoglycemia can be problematic. GLP-1 analogs are less likely to cause hypoglycemia and usually cause weight loss, but they must be injected, long-term safety data are lacking, and they are expensive; they may be a reasonable choice for young patients who cannot accept the weight gain associated with sulfonylureas and with insulin.

There are only 2 GLP-1 analogs available in the US: exenatide, which is marketed in an immediate-release formulation injected twice daily (Byetta) and in an extended-release product injected once a week (Bydureon); and liraglutide (Victoza), which is injected once daily. An article in the January 12-18, 2013 Lancet compared once-weekly exenatide with once-daily liraglutide in 911 patients with type 2 diabetes inadequately controlled by diet, exercise and oral antidiabetic drugs. The primary endpoint was change in glycated hemoglobin (HbA1c).

This study was sponsored by the manufacturer of Bydureon. An accompanying editorial points out that this was a non-inferiority trial designed to test the hypothesis that weekly exenatide is non-inferior to liraglutide, with a prespecification that if the results did not support the hypothesis, that is, if exenatide proved to be inferior to liraglutide, the superiority of liraglutide would not be tested for statistical significance.

Exenatide did not lower glycated hemoglobin enough to satisfy the predefined criteria for non-inferiority, although it came close, and nausea, vomiting and diarrhea occurred more often with liraglutide. The “Interpretation” of the study printed in the summary and reprinted alone on the cover of the journal does not mention the failure to achieve the primary endpoint of demonstrating the non-inferiority of once-weekly exenatide. It does say that both drugs improved glycemic control, that reductions in HbA1c were greater with liraglutide, and that: “These findings, plus differences in injection frequency and tolerability, could inform therapeutic decisions for treatment of patients with type 2 diabetes.”

I have to confess that I skimmed through the front and back pages of that issue of The Lancet looking for an (other?) advertisement for Bydureon, but couldn’t find any.

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  1. As a physician and a type II diabetic I have struggled with understanding the effectiveness and safety of this category of drugs. Twice daily Byetta and the potential risk of pancreatitis has disuaded me from considering this routine. Once weekly Bydureon has appeal, but data on effetivenss and safety have not been readily found in the literature that I see. Cost of these products will clearly be an issue for some patients, especially those on Medicare. Is there any data comparing the effects of these on A-1-c versus long acting insurlin?

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