Relationship between HbA1C 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 HbA1c (mean ± SE, 7.2 ± 0.1 vs. 7.7 ± 0.1%, p < 0.0001) and all meals combined post-prandial 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 HbA1c at endpoint; for every 1% reduction in HbA1c, the increase (in slope) was 1.4 episodes/patient/year (p = 0.04). Patients with confirmed hypoglycaemia had lower HbA1c than patients without hypoglycaemia (7.39 vs. 7.64%, respectively; decrement = 0.26%, p = 0.026). Conclusions These studies demonstrated an inverse relationship between HbA1c and 24-h and daytime hypoglycaemia. Lispro insulin mixtures provided lower HbA1c 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 © 2009 John Wiley & Sons, Ltd.