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Comparing Medications for Adults With Type 2 Diabetes

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Rationale for Update

In 2007, the Agency for Healthcare Research and Quality (AHRQ) published its first systematic review on the comparative effectiveness of oral hypoglycemic medications for type 2 diabetes. This comprehensive review was unique because it included comparisons of all oral diabetes medications. It also had a broad scope, including both intermediate outcomes like glycemic control and clinical outcomes like cardiovascular disease and nephropathy, as well as adverse events. This review of 216 studies concluded that most oral diabetes medications had a similar effect on reducing HbA1c, most drugs except for metformin and acarbose caused increases in body weight, and only metformin decreased low-density lipoprotein cholesterol. There were too few studies to support any conclusions about differential effects of the oral diabetes medications on all-cause mortality, cardiovascular mortality and morbidity, and microvascular complications. The sulfonylurea class was shown to be associated with an increased risk of hypoglycemia, metformin with gastrointestinal problems, and the thiazolidinediones with heart failure. In the years following publication of that review, enough studies were published to merit an update to address research gaps and integrate newer evidence. Since the first review, the Food and Drug Administration (FDA) approved two new medication classes. The noninsulin injectable GLP-1 receptor agonists, exenatide, and liraglutide, were FDA-approved in 2005 and 2010, respectively. The DPP-4 inhibitors, sitagliptin and saxagliptin, were FDA-approved in 2006 and 2009, respectively. Additionally, an update of the review was needed to include evidence about combinations of medications, including combinations of medications with insulin therapy. The updated report built upon the previous evidence report by focusing on the most important issues without seeking to replicate all parts of the previous report. Thus, the current evidence report focuses on the head-to-head comparisons of medications that should be of greatest relevance to clinicians and their patients.