Comparison of the Glycemic Effects of Rosiglitazone and Pioglitazone in Triple Oral Therapy in Type 2 Diabetes

Abstract

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...

Insulin glargine compared to NPH among insulin-naïve, U.S. inner city, ethnic minority type 2 diabetic patients

“…Hypoglycemic event rates were analyzed across groups using the Kruskal-Wallis test, proportions of subjects were analyzed using the χ 2 test, and DTSQ scores using ANCOVA. Based on our previously published HbA 1c levels in oral agent-treated patients from our clinic [16], enrollment of 24 subjects in each of the 3 treatment arms (72 subjects total) would provide 95% power to detect an HbA 1c difference of 0.8%, at a 5% significance level.…”

Hidden Complexities in Assessment of Glycemic Outcomes

“…Individuals in whom therapy with two oral agents has failed may be reluctant to start insulin therapy because of valid concerns regarding the benefits, risks, costs, and time requirements of insulin treatment (8). However, thiazolidinediones have demonstrated only limited efficacy as third-line agents in achieving and maintaining A1C <7% (17), and the long-term efficacy and safety of newer classes of antiglycemic medications as third-line therapy are not yet known.…”

Sitagliptin Compared with Thiazolidinediones as a Third-Line Oral Antihyperglycemic Agent in Type 2 Diabetes Mellitus

“…The clinic operates according to a standard treatment protocol, patterned after the American Diabetes Association guidelines (3), that involves incremental therapy with metformin followed by sulfonylureas and then TZDs, each escalated to maximally tolerated dosages, followed by initiation of basal insulin if a HbA 1c target less than 7.5% is still not achieved (as described previously [8]). We use this HbA 1c threshold for starting insulin because evidence not only indicates just a slight increase in the development or progression of retinopathy and/or nephropathy when HbA 1c levels are between 7% and 7.5% (9–13), but starting insulin imposes a significant lifestyle change (eg, the need for self-injections and monitoring, greater hypoglycemia risk).…”

“…This precluded comparing TZDs and sitagliptin as third-line oral antihyperglycemic agents in an appropriate randomized controlled trial. Therefore, the effect of sitagliptin as a third-line antihyperglycemic agent was evaluated prospectively and compared with our published experience with TZDs (8). While this design is not ideal, in the intervening years since our previous publication, there have been no changes in the oral agents available on our clinic’s diabetes drug formulary or the clinic’s treatment algorithms that govern the sequential use of different oral agent classes, so the TZD-treated control patients were cared for in the exact same fashion as the current patients receiving sitagliptin.…”

“…We have previously established the equivalence of rosiglitazone and pioglitazone as third-line oral agents in non–insulin-requiring type 2 diabetes within our institution’s indigent population (8). We therefore compared the use of sitagliptin with the use of TZDs in our historical sample when sitagliptin was used as the third-line oral agent under an identical treatment algorithm.…”