When Basal Insulin Plus Metformin Is Not Enough: Bolus Insulin or GLP1 Agonist?
When lifestyle intervention is insufficient to attain control, pharmacologic treatment of type diabetes (T2DM) is generally initiated with metformin, unless contraindications exist or GI intolerance occurs. Second step pharmacotherapy choices are diverse, but use of basal insulin is a common next step. If glycemic goals are not attained with the metformin/basal insulin combination, whence next?
Since post-prandial glucose excursions are typically the main component of excess glucose load once metformin and basal insulin have been optimized, a logical next step has been to incorporate mealtime (bolus) rapid acting insulin analogues. Unfortunately, despite the success that may be attained with this methodology, weight gain from the additional insulin is not uncommon, and the incidence of hypoglycemic episodes typically increases.
GLP1 agonists can have particular efficacy for postprandial glucose excursions also. This head-to-head trial compared outcomes of adding bolus insulin vs exenatide for patients who had not attained A1c goals (mean baseline A1c = 8.3%) on metformin plus basal insulin. Patients (n = 627) were treated for 30 weeks.
At the conclusion of the trial, A1c reductions were essentially equivalent for GLP1 agonist or bolus insulin as add-on to metformin/basal insulin (1.1% decrease in A1c for either add-on). As would be anticipated, weight decreased with exenatide and increased with bolus insulin.
Patients not at goal with the combination of metformin plus basal insulin may achieve similar levels of control by adding either a GLP1 agonist or bolus insulin, albeit with significant weight change differences.