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The Efficacy of Saxagliptin in Combination Therapy

Saxagliptin shows improved glycemic control when added to other classes of medications in type 2 diabetes patients…

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that works by extending the half-life of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The medication can be used as monotherapy or in combination with other agents for optimal glycemic control in type 2 diabetes patients. The use of combination therapy utilizes medications that offer different mechanisms of action for improved glycemic control. Combination therapy can also allow for lower doses of the medications and reduce potential for unwanted side effects.

This study examined the efficacy of saxagliptin when used in combination therapy with metformin, a sulfonylurea, a thiazolidinedione or insulin. It also examined saxagliptin’s use in triple therapy with metformin and a sulfonylurea. Separate randomized, double-blind, placebo-controlled trials were used to test the medication’s efficacy in type 2 diabetes patients. Trials were conducted over 24 weeks. HbA1c level was selected as the measure for the primary outcome.

When 2.5 or 5mg of saxagliptin per day was added to metformin therapy, a significant amount of subjects had their HbA1c decrease to less than 7% when compared to those using metformin with a placebo ( 37.1% for 2.5 mg, 43.5% for 5 g,16.6% for placebo, P<0.0001). Those receiving saxagliptin in combination with either pioglitazone or rosiglitazone were also more likely to see an HbA1c of less than 7% (42.2% for 2.5mg, 41.8% for 5 mg, 25.6% for placebo, P=0.001). Adding 5 mg per day to insulin therapy resulted in more subjects with an HbA1c of less than 7% (17.3% vs 6.7%, p<0.001). Saxagliptin also saw positive results when used in triple therapy with metformin and a sulfonylurea when compared to those receiving a placebo in place of saxagliptin (% <7% HbA1c= 30.7% vs 9.4%, P<0.001). Finally, saxagliptin showed merit in treatment naïve subjects. A greater proportion of subjects saw an HbA1c of less than 7% when initially using a combination with metformin than on those receiving metformin monotherapy (60.3% vs 41.1%, P<0.0001).

The results of this study show the benefits of using saxagliptin in combination with other diabetes medications for adequate glycemic control. Subjects receiving saxagliptin in a combination regimen were more likely have an HbA1c of less than 7% when compared to subjects using monotherapy. In addition, the medication has the benefit of being weight neutral and unlikely to cause hypoglycemic events.

Practice Pearls:

  • DPP-4 inhibitors can be used as monotherapy or in combination with other classes if glycemic control is not adequate
  • Saxagliptin demonstrates efficacy in lowering HbA1c to less than 7% in a significant proportion of subjects when used in combination with metformin, a sulfonylurea, a thiazolidinedione and insulin
  • DPP-4 inhibitors like saxagliptin have the benefit of not causing weight gain or hypoglycemic events.

Neumiller JJ. Efficacy and Safety of Saxagliptin as Add-On Therapy in Type 2 Diabetes. Clinical Diabetes. 2014. http://clinical.diabetesjournals.org/content/32/4/170