Impact of concomitant oral glucose-lowering medications on the success of basal insulin titration in insulin-naive 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-naive 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.

Automated summary

This study aimed to investigate the influence of various oral glucose-lowering medications (OGLM) on fasting plasma glucose (FPG) and hemoglobin A(1c) (HbA(1c)) levels after titration of basal insulin. A literature search retrieved 42 publications involving insulin-naive patients with type 2 diabetes. It was found that sulfonylureas, alone or in combination with metformin, hindered basal insulin titration, resulting in lower insulin doses and more hypoglycemic episodes, leading to poorer glycemic control. In contrast, adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin was more effective in achieving target FPG and HbA(1c) levels compared to metformin alone.