Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

To determine the effects of combined therapy of gliclazide and bedtime insu lin on glycemic control and C-peptide secretion, we studied 25 patients wit h type 2 diabetes and sulfonylurea secondary failure, aged 56.8 +/- 8.3 yea rs, with a duration of diabetes of 10.6 +/- 6.6 years, fasting plasma gluco se of 277.3 +/- 64.6 mg/dl and a body mass index of 27.4 +/- 4.8 kg/m(2). P atients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedtime NPH insulin (ph ase 2), and insulin (phase 3). At the end of each period, glycemic and C-pe ptide curves in response to a mixed meal were determined. During combined t herapy, there was a decrease in all glycemic curve values (P<0.01). Twelve patients (48%) reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8) vs 66.7 kg (42.8-101.4) (P<0.05), with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose s core (C-peptide/glucose x 100) increased from 0.9 (0.2-2.1) to 1.3 (0.2-4.7 ) during combined therapy (P<0.01). Despite a 50% increase in insulin doses in phase 3 (12 U (9-30) vs 18 U(11-60); P<0.01) only 3 patients who respon ded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.0 2). A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5) vs 0.6 (0-2.15); P = 0.08) and C-peptide incremental area (2.47 (0.22-6.2) vs 1.2 (0-3.35); P = 0.07) was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before start ing insulin monotherapy, despite difficulties in predicting the response.