Saxagliptin as Add-On T2DM Therapy: Reviewing the Safety, Efficacy
the MPR take:
A position statement from the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) in 2012 recommended several agents for dual and triple therapy for hyperglycemia management. A review in the journal Clinical Diabetes evaluates the safety and efficacy of saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, as an add-on therapy to metformin, sulfonylurea (SU), a thiazolidinedione (TZD), or insulin (with or without metformin), and as triple therapy with metformin and an SU. Significant improvements in A1C, fasting plasma glucose (FPG), and 2-hour postprandial glucose (PPG) were seen with saxagliptin 2.5mg and 5mg/day + metformin vs. placebo and metformin; saxagliptin + glyburide vs. placebo + uptitrated glyburide, saxagliptin 2.5mg and 5mg/day + TZD therapy vs. placebo add-on therapy, and saxagliptin + metformin and SU vs. metformin and SU + placebo. Saxagliptin 5mg/day + insulin had significant improvements in A1C and PPG only. Saxagliptin (5mg/day) + metformin was noninferior to glipizide (5mg/day titrated to 20mg/day as needed) + metformin, but saxagliptin + metformin was associated with weight loss while glipizide + metformin was associated with weight gain. Compared to metformin monotherapy, saxagliptin + metformin as initial therapy also had statistically significant reductions in A1C, FPG, and PPG from baseline. The improvements were generally sustained in long-term study extensions and follow-up studies and is generally well tolerated with a low risk of hypoglycemia or weight gain; as an add-on therapy, it may be useful for patients close to achieving their glycemic goal and who may benefit from a targeted reduction in PPG without an increased risk for hypoglycemic events.
IN BRIEF: Combination therapy for type 2 diabetes using agents with complementary mechanisms of action may improve glycemic control to a greater extent than monotherapy and allow the use of lower doses of antihyperglycemic medications. Dipeptidyl peptidase-4 inhibitors, including saxagliptin, are ...
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