Insulin glargine or NPH combined with metformin in type 2 diabetes:: the LANMET study

Aims/hypothesis: In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia. Methods: In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >= 8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups. Results: During the last 12 weeks, FPGs averaged 5.75 +/- 0.02 and 5.96 +/- 0.03 mmol/l (p < 0.001) and insulin doses were 68 +/- 5 and 70 +/- 6 IU/day (0.69 +/- 0.05 and 0.66 +/- 0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14 +/- 0.12 and 7.16 +/- 0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1 +/- 0.8 episodes/patient-year) than in the NPH+MET group (9.0 +/- 2.3 episodes/patient-year, p < 0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1 +/- 0.3 mmol/l) than in the G+MET group (8.6 +/- 0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) < 7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7 +/- 0.2 vs 6.7 +/- 0.3 mmol/l for patients reaching vs those not reaching target, p < 0.01). Conclusions/interpretation: Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinnertime hyperglycaemia compared with NPH+MET.