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DOI: 10.2337/diacare.29.03.06.dc05-0695
© 2006 by the American Diabetes Association
Emerging Treatments and Technologies |
Triple Therapy in Type 2 Diabetes
Insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naïve patients
1 Dallas Diabetes and Endocrine Center, Dallas, Texas
2 Cedar Crosse Research Center, Chicago, Illinois
3 Aventis Pharmaceuticals, Bridgewater, New Jersey
4 Aventis Pharma, Quebec, Canada
5 Diabetes and Endocrinology Scripps Clinic, La Jolla, California
Address correspondence and reprint requests to Julio Rosenstock, MD, Dallas Diabetes and Endocrine Center at Medical City, 7777 Forest Ln., C-618, Dallas, TX 75230. E-mail: juliorosenstock{at}dallasdiabetes.com
OBJECTIVE—To evaluate the efficacy and safety of add-on insulin glargine versus rosiglitazone in insulin-naïve 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 (HbA1c [A1C] 7.5–11%, BMI >25 kg/m2) 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 average 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.
Abbreviations: FPG, fasting plasma glucose • ITT, intent to treat
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