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 G erman D iabetes S tudy 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/d L ( 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.