Triple therapy in type 2 diabetes - Insulin glargine or rosiglitazone added to combmiation therapy of sulfonylurea plus metformin in insulin-naive patients

OBJECTIVE - To evaluate the efficacy and safety of add-on insulin glargine versus rosiglitazone in insulin-naive patients With type 2 diabetes inadequately controlled on dual oral therapy With sulfonylurea Plus metformin. RESEARCH DESIGN AND METHODS - in this 24-week multicenter, randomized open-label, parallel trial, 217 patients (HbA(1c), [A1C] 7.5-11%, BMI > 25 kg/m(2)) on >= 50% of maximal-dose sulfonylurea and metformin received add-on insulin glargine 10 units/day or rosiglitazone 4 mg/day. Insulin glargine was forced-titrated to target fasting plasma glucose (FPG) <= 5.5-6.7 mmol/l (<= 100-120 mg/dl), and rosiglitazone was increased to 8 mg/day any time after 6 weeks if FPG was > 5.5 mmol/l. RESULTS - A1C improvements from baseline were similar in both groups (- 1.7 vs. - 1.5% for insulin glargine vs. rosiglitazone, respectively), however, when baseline A1C was > 9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P < 0.05). Insulin glargine yielded better FPG values than rosiglitazone (-3.6 +/- 0.23 vs. -2.6 +/- 0.22 mmol/l; P = 0.001). Insulin glargine final dose per day was 38 +/- 26 IU vs. 7.1 +/- 2 mg for rosiglitazone. Confirmed hypoglycemic events at plasma glucose < 3.9 mmol/l (< 70 mg/dl) were slightly greater for the insulin glargine group (n = 57) than for the rosiglitazone group (n = 47) (P = 0.0528). The calculated aver-age rate per patient-year of a confirmed hypoglycemic event (< 70 mg/dl), after adjusting for BMI, was 7.7 (95% CI 5.4-10.8) and 3.4 (2.3-5.0) for the insulin glargine and rosiglitazone groups, respectively (P = 0.0073). More patients in the insulin glargine group had confirmed nocturnal hypoglycemia of < 3.9 mmol/l (P = 0.02) and < 2.8 mmol/l (P < 0.05) than in the rosiglitazone group. Effects on total cholesterol, LDL cholesterol, and triglyceride levels from baseline to end point with insulin glargine (-4.4, -1.4 and -19.0%, respectively) contrasted with those of rosiglitazone (+10.1, +13.1, and +4.6%, respectively; P < 0.002). HDL cholesterol was unchanged with insulin glargine but increased with rosiglitazone by 4.4% (P < 0.05). Insulin glargine had less weight gain than rosiglitazone (1.6 +/- 0.4 vs. 3.0 +/- 0.4 kg; P = 0.02), fewer adverse events (7 vs. 29%, P = 0.0001), and no peripheral edema (0 vs. 12.5%). Insulin glargine saved $235/patient over 24 weeks compared with rosiglitazone. CONCLUSIONS - Low-dose insulin glargine combined with a sulfonylurea and metformin resulted in similar A1C improvements except for greater reductions in A1C when baseline was >= 9.5% compared with add-on maximum-dose rosiglitazone. Further, insulin glargine was associated with more hypoglycemia but less weight gain, no edema, and salutary lipid changes at a lower cost of therapy.