Our data suggest that combination treatment with once-daily metformin-rosiglitazone improves glycemic control, insulin sensitivity, and beta-cell function more effectively than treatment with metformin alone.

OBJECTIVE -To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia. RESEARCH DESIGN AND METHODS-After a 4-week placebo run-in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbA 1c concentration. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbA 1c Յ7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related. RESULTSCONCLUSIONS -Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated.

OBJECTIVE -Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA 1c levels Յ7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once-or twice-daily NPH insulin in adults with type 2 diabetes.RESEARCH DESIGN AND METHODS -All studies were 24 -28 weeks long, except one 52-week study, for which interim 20-week data were used. RESULTS -Patient demographics were similar between the insulin glargine (n ϭ 1,142) and NPH insulin (n ϭ 1,162) groups. The proportion of patients achieving target HbA 1c (Յ7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P ϭ 0.0006) and nocturnal (26%; P Ͻ 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P ϭ 0.0442) and 59% (P ϭ 0.0231), respectively.CONCLUSIONS -These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA 1c target of Յ7.0% in patients with type 2 diabetes. Diabetes Care 28:950 -955, 2005T he emerging clinical paradigm is to add insulin replacement early as a "treat-to-target" strategy when oral agents are insufficient to meet the increasingly stringent glycemic targets currently recommended for type 2 diabetes management (1,2). Hypoglycemia and fear of hypoglycemia, however, remain a major barrier to treating patients with type 2 diabetes to target HbA 1c Ͻ7.0% (3,4). Furthermore, there is a growing awareness of the previously underrecognized risk of hypoglycemia, particularly nocturnal as well as severe hypoglycemia (5), and a pressing need for the prevention of hypoglycemic episodes in these patients (6,7).For many years, the most common insulin used to provide a basal insulin supply has been NPH insulin, but this intermediate-acting insulin often results in nocturnal hypoglycemia due to unwanted plasma insulin peaks, particularly during the night, as well as higher fasting glucose levels (8). Insulin glargine (LANTUS) is a long-acting basal human insulin analog with a smooth time-action profile and no pronounced peak (9). Insulin glargine appears to mimic normal physiologic basal insulin concentrations more closely compared with currently available intermediate-and long-acting insulins (10,11). In clinical trials, insulin glargine has been shown to provide an effective basal insulin supply...

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