Sitagliptin compared with thiazolidinediones as a third-line oral antihyperglycemic agent in type 2 diabetes mellitus.

OBJECTIVE: To compare sitagliptin and thiazolidinediones as third-line oral antihyperglycemic agents among ethnic minority patients with poorly controlled type 2 diabetes mellitus. METHODS: In an open-label, single-arm design, we treated type 2 diabetic patients who had suboptimal diabetes control on maximum tolerated dosages of metformin plus sulfonylureas with the addition of sitagliptin, 100 mg daily, and compared their responses with findings from a historical control group of similar patients treated with rosiglitazone, 8 mg daily, or pioglitazone, 45 mg daily, as their third-line oral agent. Patients were assessed bimonthly, and those who achieved hemoglobin A1c levels less than 7.5% at 4 months continued through 1 year of follow-up. RESULTS: One hundred eight patients were treated with sitagliptin, and 104 patients constituted the historical control group treated with rosiglitazone or pioglitazone. At baseline, sitagliptin- and thiazolidinedione-treated patients had identical hemoglobin A1c levels (mean ± SD) (9.4 ± 1.8% and 9.4 ± 1.9%, respectively) and similar known diabetes duration (6.7 ± 5.0 years and 7.6 ± 5.8 years, respectively). Hemoglobin A1c was reduced in both groups at 4 months (P<.001), but the reduction was greater with thiazolidinediones than with sitagliptin (-2.0 ± 1.7% vs -1.3 ± 1.8%; P = .006), as was the proportion of patients achieving a hemoglobin A1c level less than 7.5% (62% vs 46%; P = .026). Of all patients achieving a hemoglobin A1c level less than 7.5% at 4 months, the same proportions in each group sustained their hemoglobin A1c level less than 7.5% by 12 months (59% vs 58%). Sitagliptin was well tolerated. CONCLUSIONS: Among ethnic minority patients with poorly controlled type 2 diabetes while taking maximum tolerated dosages of metformin and sulfonylureas, third-line add-on therapy with a thiazolidinedione controlled hyperglycemia more effectively than sitagliptin after 4 months.

U-500 regular insulin: clinical experience and pharmacokinetics in obese, severely insulin-resistant type 2 diabetic patients.

OBJECTIVE: To describe the clinical experience and the pharmacokinetics of U-500 regular insulin in severely insulin-resistant obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Patients requiring >200 units of insulin with A1C levels >8.0% were switched to U-500 regular insulin. For the pharmacokinetic study, fasting subjects received 100 units of U-500 regular insulin subcutaneously, and samples drawn before and every 30-60 min for glucose, insulin, and C-peptides until glucose fell below 100 mg/dl. RESULTS: U-500 regular insulin doses were adjusted using the same approach as for adjusting NPH insulin doses. Mean values at baseline and at minimum A1C levels were, respectively, A1C 9.9 and 7.1%, 3.2 and 3.3 units/kg, and weight 98.6 and 102.8 kg. Pharmacokinetically, insulin concentrations rose briskly by 30 min and remained elevated for at least 7 h. CONCLUSIONS: Uncontrolled severely insulin-resistant obese type 2 diabetic patients can be satisfactorily controlled with U-500 regular insulin.