Effect of Two Starting Insulin Regimens in Patients with Type II Diabetes not Controlled on a Combination of Oral Antihyperglycemic Medications

Abstract

In an open-label, 24-week, parallel-group study, 135 patients inadequately controlled with oral antihyperglycemic medications (OAMs) were treated with maximally tolerated doses of metformin and glibenclamide for at least 8 weeks and then randomized to bedtime neutral protamine Hagedorn (NPH) insulin plus maximally tolerated dose of glibenclamide BID (glib/NPH group) or insulin lispro mix 50 (50% lispro, 50% insulin lispro protamine suspension [ILPS]) pre-breakfast and lispro mix 25 (25% lispro, 75% ILPS) pre-dinner (LM50/LM25 group) (both OAMs discontinued). The LM50/LM25 group had significantly lower 2-hour postprandial BG (both meals combined) compared with glib/NPH after 12 (11.70±3.40 mmol/L vs. 13.15±2.44 mmol/L, p=0.010) and 24 weeks (11.13±3.31 mmol/L vs. 14.46±2.93 mmol/L, p=0.0001). Both regimens significantly decreased HbA1c. The reduction was greater with LM50/LM25 (−1.31±2% vs. −0.5±1.6%; p=0.01). At endpoint, the overall hypoglycemia rate increased with LM50/LM25 and decreased with glib/NPH compared with baseline (0.22±0.9 vs. −0.08±0.72 episodes/patient/30 days; p=0.037). Treatment with LM50/LM25 compared with glib/NPH in patients with inadequate control on combined OAMs yielded better postprandial and overall glycemic control with a higher rate of hypoglycemia.

Key words

postprandial blood glucose - combination of glibenclamide and metformin - combination of glibenclamide and NPH insulin - insulin lispro mixtures

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1 Portions of this work were presented at the American Diabetes Association Annual Meeting, June 14 – 18, 2002, San Francisco, California: Milicevic Z, Herz M, Ivanyi T, Metcalfe S, Hancu N, Car N, Jermendy G, Mittermayer B. Sulfonylurea (SU) and bedtime NPH insulin vs. Humalog® Mix50 before breakfast and Humalog® Mix25 before dinner in patients failing combined oral treatment, Diabetes 2002;51(Suppl 2):A475, and the European Association for the Study of Diabetes, 2002: Milicevic Z, Festa A, Metcalfe S, Post-dinner and fasting glucose values are independently related to HbA1C in patients with type 2 diabetes, Diabetologia 2002;45(Suppl 2):A246.

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