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DPP-4 Inhibitors in Combination with Insulin Therapy for Type 2 Diabetes Patients

The addition of a DPP-4 inhibitor decreased HbA1C while not requiring an increase in insulin, and subjects remained weight neutral without experiencing an increase in hypoglycemic events…

Currently approved dipeptidyl peptidase-4 (DPP-4) inhibitors include alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin. DPP-4 inhibitors work by enhancing glucose dependent insulin secretion and reducing glucagon release. Adding a DPP-4 inhibitor to the regimen of a diabetes patient already receiving insulin could be beneficial if this reduced the need for a higher insulin dose which would increase the chance of weight gain and hypoglycemia.

The purpose of this study was to examine the results of randomized controlled clinical trials in which DPP-4 inhibitors were used in combination with insulin therapy. The outcomes measured included change in HbA1c levels, weight loss, change in insulin dose, risk of hypoglycemia and the overall safety profile.

Results showed that maximum HbA1c lowering was observed after 8-12 weeks of treatment. From a baseline HbA1c of 8.3-9.3%, DPP-4 inhibitors decreased HbA1c by 0.6-0.8%. No significant difference was observed in lowering insulin dose. In many of the trials, insulin dose was intended to remain stable for the trial duration. Changes in body weight were either not observed or were not significant when compared to placebo. Risk of hypoglycemia was not significantly different when compared to placebo. Overall, the safety and tolerability profile compared favorably with the placebo.

Researchers concluded that the glucose-lowering effect of adding a DPP-4 inhibitor to a type 2 diabetes patient already receiving insulin was found to decrease HbA1C. The medications were also well tolerated in most patients. With the insulin dose held constant in most studies, the risk of hypoglycemia did not increase when a DPP-4 inhibitor was added. This demonstrates that an insulin dose reduction is not needed to avoid hypoglycemia. While previous studies have shown sulfonylureas in combination with insulin have led to more hypoglycemic events that was not the case with this class of medications. In uncontrolled patients where hypoglycemia and weight gain could be a concern, the addition of a DPP-4 inhibitor might be a viable option rather than increasing the insulin dose.

Practice Pearls:

  • Increasing the dose of insulin also increases the risk for hypoglycemic events and weight gain
  • The addition of a DPP-4 inhibitor was found to decrease the HbA1C while not requiring an increase in insulin requirement
  • Subjects remained weight neutral and did not experience an increase in hypoglycemic events when a DPP-4 inhibitor was added to therapy

Frandsen CSS and Madsbad S. Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin treatment in patients with Type 2 diabetes: a review. Diabetic Medicine. 2014