Background Sulfonylurea drugs have been the only oral therapyavailable for patients with non-insulin-dependent diabetes mellitus(NIDDM) in the United States. Recently, however, metformin hasbeen approved for the treatment of NIDDM.
Methods We performed two large, randomized, parallel-group,double-blind, controlled studies in which metformin or anothertreatment was given for 29 weeks to moderately obese patientswith NIDDM whose diabetes was inadequately controlled by diet(protocol 1: metformin vs. placebo; 289 patients), or diet plusglyburide (protocol 2: metformin and glyburide vs. metforminvs. glyburide; 632 patients). To determine efficacy we measuredplasma glucose (while the patients were fasting and after theoral administration of glucose), lactate, lipids, insulin, andglycosylated hemoglobin before, during, and at the end of thestudy.
Results In protocol 1, at the end of the study the 143 patientsin the metformin group, as compared with the 146 patients inthe placebo group, had lower mean (±SE) fasting plasmaglucose concentrations (189±5 vs. 244±6 mg perdeciliter [10.6±0.3 vs. 13.7±0.3 mmol per liter],P<0.001) and glycosylated hemoglobin values (7.1±0.1percent vs. 8.6±0.2 percent, P<0.001). In protocol2, the 213 patients given metformin and glyburide, as comparedwith the 209 patients treated with glyburide alone, had lowermean fasting plasma glucose concentrations (187±4 vs.261±4 mg per deciliter [10.5±0.2 vs. 14.6±0.2mmol per liter], P<0.001) and glycosylated hemoglobin values(7.1±0.1 percent vs. 8.7±0.1 percent, P<0.001).The effect of metformin alone was similar to that of glyburidealone. Eighteen percent of the patients given metformin andglyburide had symptoms compatible with hypoglycemia, as comparedwith 3 percent in the glyburide group and 2 percent in the metformingroup.
In both protocols the patients given metformin had statisticallysignificant decreases in plasma total and low-density lipoproteincholesterol and triglyceride concentrations, whereas the valuesin the respective control groups did not change. There wereno significant changes in fasting plasma lactate concentrationsin any of the groups.
Conclusions Metformin monotherapy and combination therapy withmetformin and sulfonylurea are well tolerated and improve glycemiccontrol and lipid concentrations in patients with NIDDM whosediabetes is poorly controlled with diet or sulfonylurea therapyalone.
Source Information
From the Diabetes Division, University of Texas Health Science Center, San Antonio (R.A.D.), and Lipha Pharmaceuticals, New York (A.M.G.).
Address reprint requests to Dr. DeFronzo at the Diabetes Division, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78284.
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