Impact of concomitant oral glucose-lowering medications on the success of basal insulin titration in insulin-naïve patients with type 2 diabetes: a systematic analysis

Basal insulin treatment for type 2 diabetes is usually initiated on a background of oral glucose-lowering medications (OGLM). We wanted to examine the influence of various OGLMs on fasting plasma glucose (FPG) and hemoglobin A(1c) (HbA(1c)) values achieved after titration. A PubMed literature search retrieved 42 publications (clinical trials introducing basal insulin in 17 433 insulin-naïve patients with type 2 diabetes on a defined background of OGLM) and reporting FPG, HbA(1c), target achievement, hypoglycemic events, and insulin doses. 60 individual study arms were grouped by OGLM (combinations) allowed during the titration process: (a) metformin only; (b) sulfonylureas only; (c) metformin and sulfonylureas; or (d) metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. For all OGLM categories, weighted means and SD were calculated for baseline and end-of-treatment FPG, HbA(1c), target achievement, incidence of hypoglycemic events, and insulin doses. Primary end point was a difference in FPG after titration between OGLM categories. Statistics: analysis of variance and post hoc comparisons. Sulfonylureas, alone or in combination with metformin, impair the titration of basal insulin (insulin doses 30%–40% lower, more hypoglycemic episodes), thus leading to poorer final glycemic control (p<0.05 for FPG and HbA(1c) after titration). Conversely, adding a DPP-4 inhibitor to metformin is superior to metformin alone (p<0.05 for FPG and HbA(1c) achieved) in patients with type 2 diabetes initiating basal insulin therapy. In conclusion, OGLM are a major determinant of the success of basal insulin therapy. Sulfonylureas impair, while DPP-4 inhibitors (added to metformin) may facilitate the achievement of ambitious fasting glucose targets. PROSPERO registration number CRD42019134821.