Improved glycemic control with use of oral hypoglycemic therapy with or without insulin

To determine whether combination oral hypoglycemic therapy in insulin-using patients with non-insulin-dependent diabetes mellitus (NIDDM) can improve glycemic control for a prolonged period.

We expanded and extended an earlier study to include 130 patients with NIDDM for 10 to 30 years who had been using twice-daily mixed insulin for less than 10 years. Reduction and eventual elimination of the insulin therapy and substitution of metformin and a sulfonylurea were attempted. At follow-up visits, patients were weighed, random plasma glucose levels were determined, and glycosylated hemoglobin values were obtained.

Of 130 C-peptide-positive patients with NIDDM receiving twice-daily mixed insulin, 100 were successfully transferred to combination oral hypoglycemic therapy with glyburide originally and later glimepiride and metformin--a primary failure rate of 23.1%. Secondary failure occurred in 20 patients after a mean duration of 6.4 months. Two patients with successful conversion to oral combination therapy resumed insulin treatment because of cost. Of the patients with primary failures, 6 had gastrointestinal side effects, 10 were successfully managed on combination oral therapy plus evening mixed insulin, and 14 ultimately received twice-daily insulin and metformin. Of the secondary failures, 13 were controlled on combination oral therapy plus evening insulin and 7 on twice-daily insulin in conjunction with metformin. No difference was found in the original C-peptide levels among these three groups. Glycosylated hemoglobin levels were significantly less on combined oral hypoglycemic therapy (9.8% versus 8.3%; P = 0.0001), on combination oral therapy plus evening insulin (11.2% versus 9.7%; P = 0.001), and on return to twice-daily mixed insulin with metformin (11.0% versus 9.9%; P = 0.04). Those eight patients who resumed twice-daily insulin therapy alone, however, had a nonsignificant increase in glycosylated hemoglobin (9.3% versus 9.9%).

Improvement in glycosylated hemoglobin level in insulin-using patients with NIDDM can be obtained with combination oral therapy alone, combination oral therapy with once-daily evening insulin, or twice-daily mixed insulin with metformin in comparison with twice-daily insulin alone.