Relationship Between Hba(1c) And Hypoglycaemia In Patients With Type 2 Diabetes Treated With Different Insulin Regimens In Combination With Metformin

Background To examine the relationship between glycaemic control and hypoglycaemia in patients with type 2 diabetes treated with metformin (Met) and either insulin lispro mixtures, given twice or thrice daily (LM + Met), or insulin glargine, given once daily (G + Met).Methods Data from three randomized clinical trials were pooled to compare effects of LM + Met with G + Met.Results The LM + Met group achieved lower mean HbA(1c) (mean SE, 7.2 +/- 0.1 vs. 7.7 +/- 0.1%, p < 0.0001) and all meals combined postprandial blood glucose (BG) (8.9 +/- 0.1 vs. 10.2 +/- 0.1 mmol/L, p < 0.0001) compared with the G + Met group, but had higher fasting blood glucose (8.1 +/- 0.1 vs. 6.8 +/- 0.1 mmol/L, p < 0.0001) and insulin requirement (0.7 +/- 0.01 vs. 0.6 +/- 0.01 U/kg, p < 0.0001). Over the entire study period, daytime hypoglycaemia was higher for the LM + Met group (10.3 vs. 3.5 episodes/patient/year, p < 0.0001) than for the G + Met group; however, nocturnal hypoglycaemia was lower (3.4 vs. 6.6 episodes/patient/year, p = 0.003). At endpoint, daytime hypoglycaemia was higher for the LM + Met group (6.2 vs. 1.4 episodes/patient/year, p < 0.0001); however, nocturnal hypoglycaemia was similar in both groups (1.9 vs. 3.0 episodes/patient/year). An inverse relationship was observed between all confirmed hypoglycaemia and HbA(1c) at endpoint; for every 1% reduction in HbA(1c), the increase (in slope) was 1.4 episodes/patient/year (p = 0.04). Patients with confirmed hypoglycaemia had lower HbA(1)c than patients without hypoglycaemia (7.39 vs. 7.64%, respectively; decrement = 0.26%, p = 0.026).Conclusions These studies demonstrated an inverse relationship between HbA(1c) and 24-h and daytime hypoglycaemia. Lispro insulin mixtures provided lower HbA(1c) and post-prandial blood glucose values than glargine, but caused more daytime hypoglycaemia. Frequency of nocturnal hypoglycaemia was similar and severe hypoglycaemia was rare with both insulin regimens. Copyright (c) 2009 John Wiley & Sons, Ltd.