Repaglinide in combination therapy with metformin in Type 2 diabetes

Results are presented of a double-blind, Australian multicentre study of the efficacy and safety of adjunctive repaglinide in patients with Type 2 diabetes who were controlled inadequately on metformin monotherapy. Patients had to have been on metformin for at least 6 months and to have glycated haemoglobin (HbA1c) levels of more than 7.1%. Patients were randomized to one of three treatment regimens: metformin plus placebo (MET, n = 27), repaglinide plus placebo (REP, n = 29) and metformin plus repaglinide (MET/REP, n = 27). The metformin dose remained unchanged from the prestudy dose, whereas repaglinide was titrated from 0.5 mg to 4.0 mg preprandially, depending on fasting capillary blood glucose concentration. Maintenance treatment was continued for 3 months. In the MET and REP groups, the HbA1c level decreased from 8.6% to 8.3% and from 8.6% to 8.2%, respectively; in the MET/REP group, HbA1c decreased from 8.3% to 6.9% (p < 0.001 vs. baseline; p < 0.05 vs. each monotherapy group). Overall, 59% of patients in the MET/REP group achieved a HbA1c level of less than 7.1% by the end of the study, compared with 20% and 22% in the MET and REP groups, respectively. No serious adverse events occurred that were considered to be related to study medication. Mild symptoms of hypoglycaemia were seen in the REP and MET/REP groups, in many cases during the titration phase. The combination of repaglinide with metformin was safe and well tolerated and produced a greater improvement in glycaemic control than that seen by the sum of the changes with the two agents alone.