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In A Diabetes Outcomes Progression Trial (ADOPT), rosiglitazone (RSG) was shown to decrease progression to monothempy failure relative to glyburide (GLY) and metformin (MET) in recently diagnosed type 2 diabetic patients. We previously reported that obesity at baseline was the main determinant of C-reactive protein (CRP) in these patients. While thiazolidinediones (TZDs) have been shown to reduce inflammation, as measured by high sensitivity CRP, previous studies have been short-term and small and therefore have been unable to assess whether the increased weight gain with TZDs might attenuate their effects on CRP. We examined this issue in 783 patients from the North American Cohort of ADOPT with a median follow-up of 4.0 years. The median body mass index at baseline was 32.8 kg/m² and was similar in each treatment group. The median baseline CRP values were 4.5 mg/L for RSG, 3.7 mg/L for GLY, and 4.2 mg/L for MET. All treatments decreased CRP levels from baseline, but RSG decreased CRP levels by 47.6% (95% CI = 57.8%, 35.0%, p< 0.0001) relative to GLY and 30.5% (43.3 %, 14.9%, p=0.0004) relative to MET in spite of greater weight gain with RSG compared to both GLY by 3.85 kg (95% CI=2.39, 5.31) and MET by 8.56 kg (95% CI=7.16, 9.95). Thus, although the mechanism is unclear, RSG decreases inflammation relative to metformin and glyburide in spite of greater weight gain during four years of follow up. [ABSTRACT FROM AUTHOR]

ADOPT compared initial oral monotherapies in recently diagnosed type 2 diabetic patients and found rosiglitazone to be superior to metformin (Met) and glyburide (Gly) as assessed by time to monotherapy failure (MF), defined as time to the first of two successive fasting plasma glucose (FPG) values >180 mg/dl. Previously, the UKPDS compared Met and sulfonylurea treatment in overweight patients (≥120% ideal body weight, mean BMI 31.4 kg/m²) and found that the A1c responses to therapy were similar. We present here the ADOPT results comparing the efficacy of Met and Gly, which was a prespecified secondary analysis. Eligible patients had type 2 diabetes diagnosed within 3 years, were 30-75 years of age, and had FPG levels between 126-180 mg/dl with lifestyle management alone. Mean BMI was 32.2 kg/m². 1454 patients were randomized to Met and 1441 to Gly. Study medication was titrated to a total daily dose of 2 g Met or 15 mg Gly. Compared to Gly, Met reduced the risk of MF by 46.5% (p<0.01). At 4 years, 36% in the Met group and 26% in the Gly group remained on monotherapy and had A1c <7% (p<0.01). From a longitudinal linear model, mean A1c <7% was maintained until the 45 month visit in the Met group and the 33 month visit in the Gly group. More Met-treated patients experienced gastrointestinal adverse events (38% vs. 22%, p<0.01) but fewer experienced hypoglycemia (12% vs. 39%, p<0.01). There was weight gain at 4 years with Gly but not with Met (1.81 kg vs -2.53 kg, p<0.01). In conclusion, ADOPT demonstrated that in recently diagnosed patients with type 2 diabetes, Met is more effective than Gly, providing more durable glycemic control with less hypoglycemia and no weight gain. [ABSTRACT FROM AUTHOR]

The article highlights a study regarding the phenotypic features that influence monotherapy failure (MTF) in a diabetes outcome progression trial (ADOPT). It was found that increasing age was associated with decreasing risk of MTF and lengthen time to MTF for rosiglitazone (RSG), metformin (MET) and glyburide (GLY) therapies. For MET and GLY, higher HbA1c and FPG levels decrease time to MTF. For RSG, higher HOMA%S levels delay MTF while lower HOMA%B levels and higher HbA1c levels reduce time.