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 A1c (HbA1c) 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, HbA1c, 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, HbA1c, 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 HbA1c after titration). Conversely, adding a DPP-4 inhibitor to metformin is superior to metformin alone (p<0.05 for FPG and HbA1c 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.

Impact of the Fasting Plasma Glucose Titration Target on the Success of Basal Insulin Titration in Insulin-Naïve Patients with Type 2 Diabetes: A Systematic Analysis.

Background/Aim: We aimed to examine beneficial and adverse outcomes of basal insulin titration performed with different fasting plasma glucose (FPG) titration targets (TT). Methods: A PubMed literature search retrieved 43 reported prospective clinical trials introducing basal insulin in 17643 insulin-naïve patients with type 2 diabetes reporting fasting plasma glucose (FPG), HbA1c, target achievement, hypoglycemic events, and insulin doses. 61 individual study arms were grouped by fasting plasma glucose titration target (TT; 1: ≤5.0 mmol/l/90 mg/dl; 2: 5.01-5.6 mmol/l/90-100 mg/dl; and 3: ≥5.61 mmol/l/101 mg/dl). Weighted means and their standard deviations were calculated for baseline and end-of-treatment FPG (primary endpoint), HbA1c, target achievement, hypoglycemic events, insulin doses, and body weight gain and compared over a duration of 31 ± 10 weeks. Results: Achieved FPG and HbA1c at the end of the study were significantly lower (by up to 0.8 mmol/l or 0.23%, respectively) with more ambitious TTs (p < 0.0001), leading to better HbA1c target achievement with more ambitious TTs (by up to 14.6% for HbA1c ≤ 6.5%), without increasing the risk for hypoglycemic episodes. Conclusions: Aiming for a lower FPG TT improves glycemic control without increasing the risk for hypoglycemia.