Impact of insulin sensitivity, beta-cell function and glycaemic control on initiation of second-line glucose-lowering treatment in newly diagnosed type 2 diabetes

Aims: The aim of this study was to investigate whether insulin sensitivity, beta-cell function or glycaemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes. Research design and methods: Type 2 diabetes patients (n = 138) undergoing initial metformin monotherapy (age [mean +/- SD], 52 +/- 10 years; 67% males; BMI, 32 +/- 6 kg/m(2)) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under care of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp, M value; i.v. glucose tolerance test, incremental C-peptide area under the curve(0-60 minutes), CP iAUC). The associations of baseline M value, CP iAUC, fasting glucose and HbA1c with time to second-line therapy were assessed using parametric survival analysis, accounting for interval-censoring. Results: Second-line treatment was initiated in 26% of newly diagnosed type 2 diabetes patients within the first 3.3 years after diagnosis, using mostly DPP-4 inhibitors or GLP-1 receptor agonists (64%). In age-, sex- and BMI-adjusted survival models, higher baseline HbA1c and fasting glucose values were associated with earlier treatment intensification. Lower baseline M value and C-peptide secretion (CP iAUC) were also related to an earlier initiation of second-line treatment. In the best multivariable model, baseline HbA1c >= 7% (hazard ratio, HR; 95% CI: 3.18; 1.35-7.50) and fasting glucose >= 140 mg/dL (HR, 2.45; 95% CI, 1.04-5.78) were associated with shorter time to second-line therapy, adjusting for age, sex and BMI. Conclusions: Baseline hyperglycaemia is a strong predictor of requirement of early intensification of glucose-lowering therapy in newly diagnosed type 2 diabetes.