PMID- 15200747 OWN - NLM STAT- MEDLINE DCOM- 20040921 LR - 20181130 IS - 0300-7995 (Print) IS - 0300-7995 (Linking) VI - 20 IP - 6 DP - 2004 Jun TI - Efficacy and tolerability of initial combination therapy with nateglinide and metformin in treatment-naive patients with type 2 diabetes. PG - 883-9 AB - OBJECTIVE: To assess the efficacy and tolerability of the combination of nateglinide (120 mg, ac) and metformin (500 mg, tid) as initial treatment in drug-naive patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This study reports data from the treatment-naive (TN) subgroup of patients in a previously published, randomized, multicenter, placebo-controlled, 24- week trial that compared nateglinide, metformin, and the combination therapy (CT) in 701 patients with T2DM with baseline HbA(1c) between 6.8% and 11.0%. Of the 401 TN patients, 104, 104, 89, and 104 patients received nateglinide (120 mg, ac), metformin (500 mg, tid), CT, and placebo, respectively. The baseline characteristics of each group were similar, with mean age, BMI, duration of diabetes, HbA(1c), and fasting plasma glucose (FPG) levels of approximately 58 years, 30 kg/m(2), 4 Gastrointestinal side effects occurred in 27% of years, 8.2%, and 10.2 mmol/L, respectively. RESULTS: In patients receiving initial CT, HbA(1c) decreased substantially (Delta = -1.6 +/- 0.1%, p < 0.0001 vs. baseline or placebo) from a mean baseline of 8.2 +/- 0.1%, an effect significantly greater than the 0.8% reduction observed with both monotherapies (p < 0.001); whereas, in placebo-treated patients, HbA(1c) increased modestly (Delta = +0.3 +/- 0.1%, p < 0.05) from an identical baseline value. Seventy percent of CT-treated patients achieved a target HbA(1c) of < 7.0%. Both fasting plasma glucose (FPG) and the 2-hour postprandial glucose excursion (PPGE) after a liquid meal challenge decreased by 2.3 mmol/L in patients receiving CT, while the changes from baseline values in FPG and PPGE were +0.2 +/- 0.3 mmol/L and -0.5 +/- 0.2 mmol/L, respectively, in placebo-treated patients. The incremental 30-minute post-load insulin levels increased by 88 +/- 32 pmol/L (p = 0.006) in patients receiving CT and did not change significantly in placebo-treated patients. patients receiving CT (vs. 27.9% in the metformin monotherapy, and 14.4% in the placebo groups). Confirmed hypoglycemia (glucose