Thiazolidinedione Users Research Articles

Effect of contraindicated drugs for heart failure on hospitalization among seniors with heart failure: A nested case-control study.

Little is known about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (TZDs), nifedipine and nondihydropyridine calcium channel blockers (CCBs) usage on the risk of all-cause hospitalization among seniors with heart failure (HF). We assessed the risk of all-cause hospitalization associated with exposure to each of these drug classes, in a population of seniors with HF.Using the Quebec provincial databases, we conducted a nested case-control study in a population of individuals aged ≥65 with a first HF diagnosis between 2000 and 2009. Patients were considered users of a potentially inappropriate drug class if their date of hospital admission occurred in the interval between the date of the last drug claim and the end date of its days’ supply. The risks of hospitalization were estimated using multivariate conditional logistic regression.Of the 128,853 individuals included in the study population, 101,273 (78.6%) were hospitalized. When compared to nonusers, users of NSAIDs (adjusted odds ratio: 1.16; 95% confidence interval: 1.13–1.20), TZD (1.09; 1.04–1.14), and CCBs (1.03; 1.01–1.05) had an increased risk of all-cause hospitalization, but not the users of nifedipine (1.00; 0.97–1.03).Seniors with HF exposed to a potentially inappropriate drug class are at increased risk of worse health outcomes. Treatment alternatives should be considered, as they are available.

Use of thiazolidinediones and the risk of elective hip or knee replacement: a population based case-control study.

Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs. A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n=94609) were defined as patients >18years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use. There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR. Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs.

Thiazolidinediones and Parkinson Disease: A Cohort Study.

Thiazolidinediones, a class of medications indicated for the treatment of type 2 diabetes mellitus, reduce inflammation and have been shown to provide a therapeutic benefit in animal models of Parkinson disease. We examined the association between treatment with thiazolidinediones and the onset of Parkinson disease in older individuals. We performed a cohort study of 29,397 Medicare patients enrolled in state pharmaceutical benefits programs who initiated treatment with thiazolidinediones or sulfonylureas during the years 1997 through 2005 and had no prior diagnosis of Parkinson disease. New users of thiazolidinediones were propensity score matched to new users of sulfonylureas and followed to determine whether they were diagnosed with Parkinson disease. We used Cox proportional hazards models to compare time to diagnosis of Parkinson disease in the propensity score-matched populations. To assess the association with duration of use, we performed several analyses that required longer continuous use of medications. In the primary analysis, thiazolidinedione users had a hazard ratio for a diagnosis of Parkinson disease of 1.09 (95% confidence interval: 0.71, 1.66) when compared with sulfonylurea users. Increasing the duration-of-use requirements to 10 months did not substantially change the association; the hazard ratios ranged from 1.00 (95% confidence interval: 0.49, 2.05) to 1.17 (95% confidence interval: 0.60, 2.25). Thiazolidinedione use was not associated with a longer time to diagnosis of Parkinson disease than was sulfonylurea use, regardless of duration of exposure.

Association between Use of Oral Anti-Diabetic Drugs and the Risk of Sepsis: A Nested Case-Control Study.

Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P < 0.001), but meglitinide (adjusted OR 1.32, 95% CI 1.25–1.40, P < 0.001) use was associated with the increased risk of developing sepsis. The risk for development of sepsis was also lower among current (adjusted OR 0.87, 95% CI 0.78–0.96) and recent (adjusted OR 0.83, 95% CI 0.73–0.94) thiazolidinedione users. Current or recent sulfonylurea use and dipeptidyl peptidase-4 inhibitor use were not significantly associated with the development of sepsis. Our results highlight the need to consider the potential pleiotropic effect of OADs against sepsis in addition to the lowering of blood glucose.

Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study.

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

Limited Impact of Drug Exposure Misclassification From Non-Benefit Thiazolidinedione Drug Use on Mortality and Hospitalizations From Saskatchewan, Canada: A Cohort Study

PurposeOur purpose was to measure the effect of non-benefit drug use on observed associations between exposure and outcome, thereby documenting an empirical example of the potential magnitude of biases introduced when exposure status is misclassified from a restrictive drug coverage policy. MethodsNew users of antidiabetic agents were identified with a 1-year washout period between January 1, 1995, and December 31, 2005, in Saskatchewan, Canada, and were followed until December 31, 2008. Within this population-based cohort, persons were classified as users of benefit or non-benefit thiazolidinediones (TZDs) according to their first prescription record between January 1, 2006, and December 31, 2006 (non-benefit prescription records were not captured before 2006). An intention-to-treat approach was used to categorize TZD exposure over time. We evaluated the potential bias introduced by drug exposure misclassification by evaluating bootstrapped differences in hazard ratio (HR) estimates of all-cause hospitalization or death between users and nonusers of TZDs obtained from analyses that contained complete drug use (non-benefit and benefit drug use) versus benefit drug use only (non-benefit drug use was misclassified as unexposed). All analyses were replicated within the same cohort of new users of antidiabetic agents for clopidogrel and β-blocker (bisoprolol or carvedilol) users versus nonusers because these agents were also subject to exposure misclassification from non-benefit drug use during the period of the study. FindingsAmong 27,333 new users of antidiabetic agents, we identified 5759 TZD users (28% non-benefit) and 21,574 nonusers of TZDs. The crude HR for hospitalization or death among TZD users versus nonusers was higher in a database that contained benefit-only prescriptions than in a database that contained all prescriptions (HR = 1.11 [95% CI, 1.05–1.18] vs HR = 0.99 [95% CI, 0.94–1.04]). However, the differences in HRs after adjustment for demographic characteristics, health care utilization, comorbidities, and medications suggested minimal bias was introduced when TZD exposure was misclassified in the benefit-only database (adjusted HR [aHR] = 1.04 [95% CI. 0.98–1.10] vs aHR = 0.99 [95% CI, 0.94–1.04]; bootstrapped aHR difference = +0.05 [95% CI, 0.02–0.08]). Minimal differences in aHRs were also observed within analyses of clopidogrel (1551 users [24% non-benefit]; bootstrapped aHR difference = +0.01 [95% CI, –0.04 to 0.06]) and β-blocker users (351 users [42% non-benefit]; bootstrapped aHR difference = +0.06 [95% CI, –0.09 to 0.20]) versus nonusers. ImplicationsAlthough patient characteristics and outcomes differed between users of non-benefit and benefit drugs, misclassification of drug exposure did not meaningfully bias estimates of all-cause mortality and hospitalization after covariate adjustment in our study.

Impact of oral antidiabetic agents on bone metabolism.

Impact of oral antidiabetic agents on bone metabolism.

Thiazolodinediones and Cancer: Duplicate Publication Bias?

A meta-analysis of epidemiological studies reported no increased risk for cancer in users of thiazolidinediones; however, subanalyses showed a small 1.1- to 1.2-fold increased risk for bladder cancer with thiazolidinedione use. This analysis was probably distorted by “duplicate publication bias.”

The association between adherence to oral anti‐diabetic drugs and hypoglycaemia in persons with Type 2 diabetes

To quantify the relationship between adherence to oral anti-diabetic drugs and incident hypoglycaemia in Type2 diabetes. Utilizing a claims database, we identified patients with Type2 diabetes initiating metformin, sulphonylureas or thiazolidinediones and classified adherence over the next 6months, creating markers of changes in therapy (switches/additions). We created nine mutually exclusive exposure groups, including: metformin ≥80% adherence; metformin <80% adherence; sulphonylurea ≥80% adherence; sulphonylurea <80% adherence; thiazolidinediones ≥80% adherence; thiazolidinediones <80% adherence; switching to a new class; adding on therapy; and switching to two or more different classes of medication. We followed patients for incident hypoglycaemia medical visits and developed a Cox proportional hazards model to compare rates of hypoglycaemia across exposure groups. Adherence to monotherapy was high (86.0±17.8% for metformin, 87.2±17.5% for sulphonylureas and 87.8±16.9 for thiazolidinediones). The incidence of hypoglycaemia ranged from 93.1 to 259.9 per 10 000 person-years in the nine exposure groups. Relative to metformin users with ≥80% adherence, those switching from any monotherapy to combination therapy had a 32% increased rate (hazard ratio1.32; 95%CI 1.07-1.64) of hypoglycaemia. Thiazolidinediones users with ≥80% adherence had a decreased hazard rate (hazard ratio0.67; 95%CI 0.46-0.98) relative to metformin users with ≥80% adherence. All other groups on oral anti-diabetic drugs, regardless of adherence, were not associated with hypoglycaemia We found that the relative rate of hypoglycaemia was highest in patients switching from monotherapy to combination therapy, while rates of hypoglycaemia in monotherapy users were largely unrelated to level of adherence.

Risk of fracture with thiazolidinediones: an individual patient data meta-analysis

Background: The use of thiazolidinediones (TZDs) has been associated with increased fracture risks. Our aim was to estimate the risk of fracture with TZDs in three different healthcare registries, using exactly the same study design, and to perform an individual patient data meta-analysis of these three studies.Methods: Population-based cohort studies were performed utilizing the British General Practice Research Database (GPRD), the Dutch PHARMO Record Linkage System (RLS), and the Danish National Health Registers. In all three databases, the exposed cohort consisted of all patients (aged 18+) with at least one prescription of antidiabetic (AD) medication. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. The total period of follow-up for each patient was divided into periods of current exposure and past exposure, with patients moving between current and past use.Results: In all three registries, the risk of fracture was increased for women who were exposed to TZDs: HR 1.48 (1.37–1.60) in GPRD, HR 1.35 (1.15–1.58) in PHARMO, and HR 1.22 (1.03–1.44) in Denmark. Combining the data in an individual patient data meta-analysis resulted, for women, in a 1.4-fold increased risk of any fracture for current TZD users versus other AD drug users [adj. HR 1.44 (1.35–1.53)]. For men, there was no increased fracture risk [adj. HR 1.05 (0.96–1.14)]. Risks were increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle, and foot, but not for hip/femur or vertebral fractures. Current TZD users with more than 25 TZD prescriptions ever before had a 1.6-fold increased risk of fracture compared with other AD drug users [HR 1.59 (1.46–1.74)].Conclusion: In this study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for women using TZDs, but not for men, across three different healthcare registries. TZD users had an increased risk for fractures of the extremities, and risks further increased for prolonged users of TZDs.

Diabetes medication use and blood lactate level among participants with type 2 diabetes: the atherosclerosis risk in communities carotid MRI study.

BackgroundThe objective of this study is to compare lactate levels between users and non-users of diabetes medications under the hypothesis that the level of lactate is a marker of oxidative capacity.MethodsThe cross-sectional data of 493 participants aged 61–84 with type 2 diabetes who participated in the Atherosclerosis Risk in Communities Carotid MRI study were analyzed using survey weighted linear regression.ResultsMedian plasma lactate level was 8.58 (95% CI: 8.23, 8.87) mg/dl. Comparing users of diabetic medications with non-users, thiazolidinedione use was significantly associated with lower lactate level (7.57 (6.95–8.25) mg/dL vs. 8.78 (8.43–9.14) mg/dL), metformin use with a slightly higher lactate level (9.02 (8.51–9.58) mg/dL vs. 8.36 (7.96–8.77) mg/dL), and sulfonylurea and insulin use were not associated with lactate level. After adjustment for demographic and lifestyle factors, the plasma lactate level for thiazolidinedione users was 15.78% lower than that for non-users (p<0.001). Considering use of each medication separately and in combination did not change the results.ConclusionIn conclusion, thiazolidinedione use was associated with lower plasma lactate level compared to non-use and metformin use was only marginally associated with a slightly higher lactate level. These results are consistent with the previously demonstrated effects of diabetes medications on oxidative metabolism. Further investigation of the role that diabetes medications play in improvement of oxidative metabolism is warranted.

Association Between Thiazolidinedione Treatment and Risk of Macular Edema Among Patients With Type 2 Diabetes

Findings of prior studies have been inconclusive about the ocular effects of thiazolidinediones on diabetic macular edema (DME). We evaluated, in patients with type 2 diabetes (T2D), the short-term and long-term risks of developing DME among users vs nonusers of thiazolidinediones. A retrospective cohort study of 103,368 patients with T2D and no DME at baseline using The Health Improvement Network (THIN) database. Clinical, biochemical, and demographic information was obtained for the period January 1, 2000, through November 30, 2009. At 1 year, the incidence of DME was 1.3% (n = 41) and 0.2% (n = 227) among thiazolidinedione users (n = 3227) and nonusers (n = 100,141), respectively (odds ratio [OR], 5.7 [95% CI, 4.1-7.9]). After Cox multiple regression analysis (adjusted for age; systolic blood pressure; levels of lipids and hemoglobin A(1c); and use of aspirin, fibrates, insulin, oral antidiabetic drugs, or renin-angiotensin system blockers), multiple imputation analysis to adjust for missing values, and propensity score analysis to exclude for any selection bias, thiazolidinedione use was associated with an increased risk of DME at 1-year follow-up (OR, 2.3 [95% CI, 1.5-3.6]) and 10-year follow-up (hazard ratio [HR], 2.3; [95% CI, 1.7-3.0]). The effect was similar for pioglitazone and rosiglitazone. Combination therapy with insulin plus a thiazolidinedione was associated with a higher risk of DME after propensity score adjustment (HR, 3.0 [95% CI, 1.5-5.9]), while aspirin use (HR, 0.6 [95% CI, 0.4-0.9]) and angiotensin-converting enzyme inhibitor use (HR, 0.4 [95% CI, 0.2-0.7]) were associated with a reduced risk of DME. Among patients with T2D, treatment with a thiazolidinedione was associated with an increased risk of DME at 1-year and 10-year follow-up evaluations.

Risk of Fracture with Thiazolidinediones: Disease or Drugs?

The use of thiazolidinediones (TZDs) has been associated with an increased fracture risk. In addition, type 2 diabetes mellitus (T2DM) has been linked with fracture. We evaluated to what extent the association between TZD use and fracture risk is related to the drug or to the underlying disease. We conducted a population-based cohort study using the Danish National Health Registers (1996–2007), which link pharmacy data to the national hospital registry. Oral antidiabetic users (n = 180,049) were matched 1:3 by year of birth and sex to nonusers. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. Time-dependent adjustments were made for age, comorbidity, and drug use. We created a proxy indicator for the severity of disease. The first stage was defined as current use of either a biguanide or a sulfonyluerum, the second stage as current use of a biguanide and a sulfonyluerum at the same time, the third stage as patients using TZDs, and the fourth stage as patients using insulin. The risk of osteoporotic fracture was increased 1.3-fold for stages 3 and 4 compared with controls. Risk with current TZD use (stage 3 HR = 1.27, 95 % CI 1.06–1.52) and risk with current use of insulin (stage 4 HR = 1.25, 95 % CI 1.20–1.31) were similar. In the first (HR = 1.15, 95 % CI 1.13–1.18) and second (HR = 1.00, 95 % CI 0.96–1.04) stages risks were lower. Risk of osteoporotic fracture was similar for TZD users and insulin users. When studying fracture risk with TZDs, the underlying T2DM should be taken into account.

Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs?

Clinical and observational studies suggest that use of thiazolidinediones (TZDs) is associated with an increased fracture risk. In addition, type 2 diabetes mellitus (T2DM) is a risk factor for osteoporotic fracture. Our aim was to estimate fracture risks in TZD users and users of other antidiabetic drugs, classified according to proxies of disease severity. We conducted a population-based cohort study utilizing the Dutch PHARMO database (1998-2008). PHARMO links pharmacy-dispensing data to the National Hospital Registry. Oral antidiabetic users (n = 123,452) were matched 1:4 by year of birth and sex to non-users. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture in TZD users. We created a proxy indicator for disease severity. The first stage was defined as current use of either a biguanide or a sulfonylureum, the second stage as current use of a biguanide and a sulfonylureum at the same time, the third stage was assigned to patients using TZDs and the fourth stage to patients using insulin. The risk of osteoporotic fracture was increased 1.5-fold (HR 1.49, 95%CI 1.28-1.73) in patients who currently used TZDs (stage 3), and for patients using insulin (stage 4), the risk was increased 1.2-fold (HR 1.24, 1.14-1.36), as compared with controls. In the first and second stages, risks were lower: HR 1.11 (1.06-1.17) for stage 1 and HR 1.03 (0.96-1.11) for stage 2. When observational studies assess risk of fracture in patients with TZDs, the severity of T2DM should be taken into account.

AHRQ's comparative effectiveness research on oral medications for type 2 diabetes: a summary of the key findings.

In 2007, the Agency for Healthcare Research and Quality(AHRQ) published a systematic review on the comparative effectiveness of oral medications for type 2 diabetes. The review included studies on the benefits and risks of oral medications used for achieving glycemic control in patients with type 2 diabetes. AHRQ published an updated review in March 2011 that summarized the benefits and harms of medications (metformin,second-generation sulfonylureas, thiazolidinediones, meglitinides,dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes. To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 comparative effectiveness review on medications for adults with type 2 diabetes, (b) encourage consideration of the clinical and managed care applications of the review findings, and(c) identify limitations and gaps in the existing research with respect to the benefits and risks of oral diabetes medications. Type 2 diabetes mellitus is a major public health burden. Since the 2007 AHRQ systematic review of oral medications for type 2 diabetes, the FDA has approved several new drug classes. Therefore, in 2011, the original systematic review was updated with comparisons including the newer oral diabetes medications. The updated report expands beyond the scope of the original 2007 review by including comparisons of 2-drug combinations and the addition of more head-to-head comparisons, as well as additional adverse outcomes. A high strength of evidence showed that most medications were similarly efficacious at lowering hemoglobin A1c by about 1 absolute percentage point compared with baseline values. The addition of most oral medications to initial monotherapy further improved glycemiccontrol by lowering A1c by another 1 percentage point. The only exception was the DPP-4 inhibitor class, which did not lower A1c to the same extent as metformin when used as monotherapy. Overall, metformin was found to have a more favorable effect on body weight when compared with other medications. Two-drug combinations compared with each other demonstrated similar reductions in A1c levels. Metformin decreased low-density lipoprotein cholesterol (LDL-C) relative to pioglitazone, sulfonylureas,and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk of mild-to-moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus a thiazolidinedione. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas, and an increased risk for bone fractures relative to metformin. Diarrhea occurred more often for metformin users compared with thiazolidinedione users. Although the long-term risks and benefits of diabetes medications remain unclear, the evidence supports the use of metformin as a first-line agent.

Risk of Death and Cardiovascular Outcomes with Thiazolidinediones: A Study with the General Practice Research Database and Secondary Care Data

ObjectiveTo describe the likely extent of confounding in evaluating the risks of cardiovascular (CV) events and mortality in patients using diabetes medication.MethodsThe General Practice Research Database was used to identify inception cohorts of insulin and different oral antidiabetics. An analysis of bias and incidence of mortality, acute coronary syndrome, stroke and heart failure were analysed in GPRD, Hospital Episode Statistics and death certificates.Results206,940 patients were identified. The bias analysis showed that past thiazolidinedione users had a lower mortality risk compared to past metformin users. There were no differences between past users of rosiglitazone and pioglitazone (adjusted RR of 1.04; 95% CI 0.93–1.18). Current rosiglitazone users had an increased risk of death (adjusted RR 1.20; 95% CI 1.08–1.34) and of hospitalisation for heart failure (adjusted RR of 1.73; 95% CI 1.19–2.51) compared to current pioglitazone users. Risk of mortality was increased two-fold shortly after starting rosiglitazone. Excess risk of death over 3 years with rosiglitazone was 0.3 per 100 in those aged 50–64 years, 2.0 aged 65–74, 3.0 aged 75–84, and 7.0 aged 85+. The cause of death with rosiglitazone was more likely to be due to a disease of the circulatory system.ConclusionsHigher risks for death (overall and due to cardiovascular disease) and heart failure were found for rosiglitazone compared to pioglitazone. These excess risks were largest in patients aged 65 years or older. The European regulatory decision to suspend rosiglitazone is supported by this study.

Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies

Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis...

The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort.

Effects of oral antidiabetic drugs (OADs) on lipids may influence cardiovascular outcomes. Our aim was to compare time to initiation of lipid lowering medication (LLM) and 12-month lipid profiles among new OAD users. We identified a retrospective cohort of 17,774 veterans who received care at Veterans Administration (VA) Mid-South Network with a first OAD from 1 January 2000 to 31 December 2007. There were 6917 patients (38.9%) not on a LLM at baseline, and 3871 (56%) had complete covariates. Incident users of sulfonylurea and combination metformin + sulfonylurea were compared to metformin users for time to LLM initiation. Incident users of these OADs and thiazolidendiones were included in comparison of 12-month low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and total cholesterol. All analyses adjusted for demographics, lipids, HbA1C, healthcare utilization, and cardiovascular disease at baseline. The median time to starting LLM was 2.35 years (interquartile range 0.96, 4.6) following metformin initiation and not statistically different for users of sulfonylureas, or combination OADs. Compared to metformin users, 12-month HDL was 1.35 mg/dl (95%CI: -2.01, -0.72) lower and TGs were 5.7% higher (95%CI: 1.5%, 10.0%) for sulfonylurea users; TGs were 24.8% (95%CI: 0.7%, 54.5%) higher for thiazolidinedione users. Statin users had LDL and total cholesterol 16.7 mg/dl (95%CI: -19.9, -13.5) and 18.6 mg/dl (95%CI: -22.1, -15.1) lower than non-statin users, respectively. Time to LLM initiation was similar between OADs. Metformin use resulted in more favorable lipids at 12 months compared to sulfonylureas or thiazolidinediones.

DB4 ECONOMIC EVALUATION OF THIAZOLIDINEDIONES AS ADD-ON THERAPY FOR TREATMENT OF TYPE 2 DIABETIC PATIENTS IN THE TAIWANESE NATIONAL HEALTH INSURANCE SYSTEM

The cost-effectiveness of adding the two health insurance covered thiazolidinediones (TZDs)-rosiglitazone or pioglitazone, to metformin in treating type 2 diabetes mellitus was assessed from a Taiwanese National Health Insurance (NHI) perspective.This analysis was based on patient-level data extracted from Taiwan's NHI databases. Type 2 diabetic patients who received consecutive metformin treatments between 2001 and 2005 were identified. Clinical effectiveness, a proxy of glycemic control (time to insulin dependence), and direct medical cost were also estimated. Incremental cost-effectiveness ratio (ICER) was calculated and expressed as cost per delayed year to insulin dependence.Compared to add-on non-TZDs, add-on rosiglitazone and pioglitazone were associated with delays of additional 151 days (0.41 years) and 101 days (0.28 years) in insulin dependence, respectively. Total mean medical costs were higher in add-on TZDs users compared to add-on non-TZDs users. The additional total medical costs of add-on rosiglitazone or pioglitazone were comparable, with ICERs of 95,874 and 95,485 New Taiwan (NT) dollars per year delay in insulin dependence, respectively.Add-on TZDs improves glycemic control but also increases direct medical cost. In terms of the incremental medical costs associated with these clinical benefits, add-on rosiglitazone or pioglitazone are similar in Taiwan.

Relationship between cumulative dose of thiazolidinediones and clinical outcomes in type 2 diabetic patients with history of heart failure: a population-based cohort study in Taiwan

Thiazolidinediones (TZDs) are widely used antidiabetic agents, but there is great concern and conflicting reports over their possible effect on cardiovascular morbidity, especially in patients with heart failure (HF). Using 2000-2005 Taiwan's National Health Insurance (NHI) claims data, this population-based, retrospective cohort study investigated if there was an association between the cumulative TZD dose and clinical outcomes in type 2 diabetic patients recently hospitalized for HF. Study outcomes were death, first all-cause readmission, and first readmission for HF. Cox proportional hazard models were used to analyze the association between TZD versus sulfonylurea (SU) use and these outcomes. Out of a total of 8139 eligible patients, 224 were taking TZD (65.63% female; mean [SD] age, 68.30[10.60] years) and 7915 were taking SU (55.10% female; 70.30[10.50] years). Patients taking TZD were at higher risk for readmission for HF (59 cases; HR 1.58 (95% confidence interval, 95%CI 1.44-1.72)), all-cause readmission (147 cases; 1.40 (1.30-1.70)), and death (103 cases; 2.23 (1.58-3.14)). The higher the cumulative exposure to TZD, the greater the risk of HF readmission, all-cause readmission, and death. Among diabetic patients who had been hospitalized for HF, TZD users were at significantly greater risk for readmission for HF, all-cause readmission, and death than SU users. The risk of all adverse clinical outcomes appeared to highly relate to cumulative exposure to TZD. These findings provide empirical evidence supporting the latest black box warnings issued by the United States Food and Drug Administration in August, 2007 advising that TZD not be prescribed for diabetic patients with symptomatic heart failure.