No abstract

OBJECTIVETo describe the clinical experience and the pharmacokinetics of U-500 regular insulin in severely insulin-resistant obese type 2 diabetic patients.RESEARCH DESIGN AND METHODSPatients 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.RESULTSU-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.CONCLUSIONSUncontrolled severely insulin-resistant obese type 2 diabetic patients can be satisfactorily controlled with U-500 regular insulin.

T o date, there have been few comparison studies between rosiglitazone and pioglitazone (1,2) and none of the two thiazolidinediones (TZDs) as a third agent in triple oral therapy. In February 2003, pioglitazone replaced rosiglitazone as the TZD on the pharmacy formulary at our hospital. This gave us the opportunity to compare the effectiveness of rosiglitazone and pioglitazone added to type 2 diabetic patients already on maximum (tolerated) doses of metformin and a sulfonylurea agent whose HbA 1c (A1C) levels did not meet the American Diabetes Association goal of Ͻ7.0%.RESEARCH DESIGN AND METHODS -Our diabetes clinic treatment algorithm mandates starting small doses of either a sulfonylurea agent or metformin and increasing the dose every 2 weeks until either a fasting plasma glucose (FPG) concentration of Ͻ130 mg/dl is attained or a maximal (tolerated in the case of metformin) dose is reached. If the FPG concentration remains Ͼ130 mg/dl, the alternate drug is added and also increased every 2 weeks. When the FPG goal is achieved, further therapeutic decisions are based on A1C levels measured 2-3 months later. Only when both agents are maximized and either the FPG concentration 2 weeks after the last increase remains Ͼ130 mg/dl or an A1C level is Ն7.0% 2-3 months after the FPG goal is reached, or at any time thereafter, is a maximal dose of a TZD added. The maximal dose is used because it can take up to 4 months to see a maximal response. If lower TZD doses are used initially and titrated upward, the patient can remain out of control for up to a year before insulin is started.Four months after adding the TZD, we decided whether triple oral therapy had been successful. We chose an A1C level of Յ7.5% to designate success and not start insulin (which necessitates significant lifestyle changes) because there was only a slight increase in the development or progression of retinopathy and/or nephropathy in patients with mean A1C levels between 7 and 8% (3-7). Only when A1C levels exceeded 7.5% (measured 4 months after starting the TZD or subsequently) was bedtime insulin started.The study design was a retrospective chart review of 104 adult type 2 diabetic patients followed in our diabetes clinic. The criterion for inclusion was taking a TZD for at least 4 months in patients who had failed maximal (tolerated) doses of metformin and a sulfonylurea agent. Comparisons were made in patients at 4 months, and those with successful outcomes (A1C Յ7.5%) were followed for 8 more months. The responses of 56 consecutively treated patients, in whom 45 mg pioglitazone was added, were compared with 48 patients receiving 8 mg rosiglitazone, as reported previously (8).RESULTS -Fifty-six patients on pioglitazone (24 men and 32 women, aged 54.1 Ϯ 7.7 years [mean Ϯ SD], diabetes duration 8.3 Ϯ 5.9 years, and BMI 33.2 Ϯ 7.4 kg/m 2 ) were studied. There were 42 Latinos, 11 African Americans, 2 Caucasians, and 1 Asian Pacific Islander. At baseline, 55 patients were taking maximal doses of glyburide (20 mg) or glipizide (40 mg), with 1 pati...

No abstract

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.