Once-daily Insulin Glargine Administration in the Morning Compared to Bedtime in Combination with Morning Glimepiride in Patients with Type 2 Diabetes: An Assessment of Treatment Flexibility

Abstract

Aims: To compare the incidence of nocturnal hypoglycemia and glycemic control following bedtime or morning insulin glargine (LANTUS^®; glargine) plus glimepiride. Methods: In this 24-week, multinational, open, randomized study, 624 patients with type 2 diabetes poorly controlled on oral therapy received morning or bedtime glargine plus morning glimepiride (2, 3 or 4 mg) titrated to a target fasting blood glucose level ≤ 5.5 mmol/l. Results: The incidence of nocturnal hypoglycemia was equivalent between the two groups, with morning glargine non-inferior to bedtime (13.0 vs. 14.9 % of patients; between-treatment difference -1.9 %; one-sided 95 % confidence interval -100 %; 2.84 %). At endpoint, similar improvements in glycemic control were observed with morning compared to bedtime glargine: HbA_1c: - 1.65 ± 1.21 vs. -1.57 ± 1.16 %; p = 0.42; fasting blood glucose: - 4.25 ± 2.82 vs. -4.48 ± 2.75 mmol/l; p = 0.08. The endpoint mean daily glargine dose was comparable (34.7 ± 17.4 vs. 32.4 ± 17.0 IU; p = 0.15), and there was no significant between-treatment difference in the change in body weight (2.1 vs. 1.8 kg; p = 0.39). Conclusions: Once-daily glargine can be administered in a flexible morning or bedtime regimen (plus morning glimepiride) to achieve good glycemic control without any difference in hypoglycemia.

Key words

Basal insulin - disease duration - flexibility - oral antidiabetic agent - titration

References

• 1 Yki-Järvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group.  Diabetes Care. 2000;  23 1130-1136
• 2 Riddle M, Rosenstock J, Gerich J. Insulin Glargine 4002 Study Investigators: The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients.  Diabetes Care. 2003;  26 3080-3086
• 3 Massi Benedetti M, Humburg E, Dressler A, Ziemen M. A one-year, randomised, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with type 2 diabetes.  Horm Metab Res. 2003;  35 189-196
• 4 ADA . Standards of medical care for patients with diabetes mellitus.  Diabetes Care. 2003;  26 S33-S50
• 5 European Diabetes Policy Group . A desktop guide to type 2 diabetes mellitus.  Diabet Med. 1999;  16 716-730
• 6 Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo.  Diabetes Care. 2000;  23 644-649
• 7 Hamann A, Matthaei S, Rosak C, Silvestre L,. HOE901/4007 Study Group . A randomized clinical trial comparing breakfast, dinner, or bedtime administration of insulin glargine in patients with type 1 diabetes.  Diabetes Care. 2003;  26 1738-1744
• 8 Fritsche A, Schweitzer M, Haring H-U. 4001 Study Group: Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.  Ann Intern Med. 2003;  138 952-959
• 9 The Diabetes Control and Complications Trial Research Group . Hypoglycemia in the Diabetes Control and Complications Trial.  Diabetes. 1997;  46 271-286
• 10 The DCCT Research Group . Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial.  Am J Med. 1991;  90 450-459
• 11 Yki-Järvinen H. Combination therapies with insulin in type 2 diabetes.  Diabetes Care. 2001;  24 758-767
• 12 Home P. The challenge of poorly controlled diabetes mellitus.  Diabetes Metab. 2003;  29 101-109
• 13 Yki-Järvinen H, Ryysy L, Nikkila K, Tulokas T, Vanamo R, Heikkila M. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial.  Ann Intern Med. 1999;  130 389-396
• 14 UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).  Lancet. 1998;  352 837-853
• 15 Riddle M. Timely addition of insulin to oral therapy for type 2 diabetes.  Diabetes Care. 2002;  25 395-396