Incretin Therapy in Combination with Insulin for Type 2 Diabetes Patients

Incretin-based therapies are an intuitive option for adjuvant therapy with insulin due to…. 

Incretin-based therapies are an intuitive option for adjuvant therapy with insulin due to the glucose-dependency of their glucagon inhibition and insulin enhancing effects.

In addition, incretin therapies result in weight loss or no weight change at all, unlike insulin which often results in weight gain.

The combination of incretin-based therapy and insulin will likely be additive or synergistic without an elevated risk of hypoglycemia. One uncontrolled retrospective analysis of 188 patients (of which 70% had type 2 diabetes for greater than 10 years) whose baseline HbA1c was 8.05% while on insulin therapy, showed a further reduction of -0.66% when exenatide was added to their insulin regimen. Evidence shows that the decrease was sustained beyond 2 years in some patients.

A separate prospective 30-week placebo controlled, randomized, double blind study of 261 patients with type 2 diabetes for 12 years studied the addition of either placebo or exenatide to insulin glargine (with or without other oral antidiabetic agents). The glargine dose was decreased by 20% if the HbA1c was equal or less than 8.0%, but maintained if it was greater than 8.0%. Patients were then titrated to a fasting plasma glucose of 100mg/dL.

When exenatide was added to patients with an average baseline of 8.3%, a reduction in HbA1c of 1.74% was seen, whereas the placebo group saw a reduction of 1.04% from a baseline of 8.5%. This difference was seen even though there was an average difference of additional 7 units of insulin per dose in the placebo group.

J. Vora, S.C. Bain, T. Damci, G. Dzida, P. Hollander, L.F. Meneghini, S.A. Ross, Incretin-based therapy in combination with basal insulin: A promising tactic for the treatment of type 2 diabetes, Diabetes & Metabolism, Volume 39, Issue 1, February 2013, Pages 6-15, ISSN 1262-3636, 10.1016/j.diabet.2012.08.002.