Repaglinide Versus Metformin in Combination With Bedtime NPH Insulin in Patients With Type 2 Diabetes Established on Insulin/Metformin Combination Therapy

Abstract

OBJECTIVE—To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician’s discretion, aiming for a fasting blood glucose (FBG) ≤6.0 mmol/l. RESULTS—Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA1c (Diabetes Control and Complications Trial–aligned assay, normal range 4.6–6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 ± 0.4 kg (means ± SE) (P = 0.01) versus 2.7 ± 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 ± 0.8 to 34.1 ± 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 ± 0.9 to 29.1 ± 1.3 (P < 0.002) with insulin/repaglinide. CONCLUSIONS—Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.