Pioglitazone Users Research Articles

The effect of long-term use of pioglitazone on bone mineral density in patients with diabetes mellitus

Aims: This study aimed to explore the incidence of osteoporosis in patients with diabetes mellitus (DM) who have been on a long-term pioglitazone regimen, and to ascertain the link between pioglitazone usage and the onset of osteoporosis.
 Methods: We enrolled patients prospectively and conducted a comparative analysis between two groups of DM patients: those who had been using pioglitazone for a period exceeding two years, and those with no history of pioglitazone use. Bone Mineral Density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA).
 Results: There were no significant differences in age, gender, disease duration, fasting plasma glucose levels, and HbA1c levels between pioglitazone users and non-users. However, a significant variation was found in the BMD measurements. Patients on pioglitazone had an L1-L4 vertebra BMD T-score of -1.3, compared to -0.9 in non-users (p

The association between pioglitazone consumption and incidence of bladder cancer in type II diabetic patients: a systematic review and meta-analysis of observational studies

Background: Bladder cancer is the single most prevalent urinary tract malignancy in humans with a higher risk in diabetic patients. Pioglitazone is among the conventional antidiabetic drugs. The present study thus seeks to investigate the association between the administration of pioglitazone and the incidence of bladder cancer in type II diabetic patients through a meta-analysis and systematic analysis. Materials and Methods: International databases including Web of Science, Medline/PubMed, Scopus, and Google Scholar search engine were explored. To integrate the results of studies odds ratio (OR), risk ratio (RR) or hazard ratio (HR) logarithm was extracted from each study, and the I2 index or the Cochran’s Q test were conducted to examine the heterogeneities across studies. Data analysis was carried out in STATA version14 considering a significance level of p<0.05. Results: The 15 examined studies had investigated a total of 5,353,528 patients (1,536,723 patients in case groups and 3,816,805 patients in control groups). The relative risk of bladder cancer was [RR: 1.20 (95% CI: 1.09-1.32)] in pioglitazone users. Bladder cancer risk in pioglitazone users was higher by [RR: 1.14 (95% CI: 1.03-1.25)] compared to those who had never taken pioglitazone, [RR: 1.32 (95% CI: 1.02-1.70] compared to sulfonylurea users, and [RR: 1.57 (95% CI: 1.23-2)] compared to dipeptidyl peptidase-4 (DPP-4) users. Moreover, the relative risk between pioglitazone consumption and bladder cancer was reported to be [RR: 1.27 (95% CI: 0.96-1.68)] in patients with a follow-up shorter than five years and [RR: 1.24 (95% CI: 1.09-1.41)] is patients with a follow-up of five years or longer. On the other hand, the relative risk between pioglitazone consumption and bladder cancer was [RR: 1 (95% CI: 0.69-1.45)] in 50-59 age group, [RR: 1.20 (95% CI: 1.04-1.38)] in the 60-69 age group, and [RR: 1.33 (95% CI: 1.14-1.56)] in the 70-79 age group. Conclusion: Patients who receive pioglitazone had a 20% higher risk of bladder cancer compared to those who had not taken pioglitazone or prescribed other medication such as sulfonylurea and DPP-4s. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID: CRD42023391151).

Pioglitazone use is associated with reduced risk of Parkinson’s disease in patients with diabetes: A systematic review and meta-analysis

ObjectiveThis meta-analysis aimed to evaluate the effect of pioglitazone on Parkinson’s disease (PD) in diabetes patients. MethodsA study search was carried out in PubMed, Embase, and Web of Science databases from inception to July 22, 2021. The Newcastle-Ottawa scale was used to evaluate the quality of the eligible studies. The risk ratio (RR) and 95% confidence intervals (CI) were used as effect size indicators in this meta-analysis to evaluate the risk association between pioglitazone and PD. The Cochran’s Q and I2 tests were used to assess statistical heterogeneity. A dose–response meta-analysis was conducted using the least squares trend estimation method. ResultsThree studies were eligible for this meta-analysis. Compared with diabetes patients who did not use pioglitazone, there was a significant reduction in the risk of PD (RR of 0.87 [95 % CI 0.62–0.99, P = 0.039]) in pioglitazone users. No significant difference in PD risk was noted in diabetes patients taking 438 dose-duration-days (DDDs) of pioglitazone or lower compared with those who did not. When the DDD of pioglitazone was 438, the RR was 0.85 (95 % CI [0.72–1.00], P = 0.05). When the DDD of pioglitazone was > 438, the risk of PD in patients with diabetes was significantly decreased (P < 0.05) and showed an approximate linear correlation trend. ConclusionPioglitazone administration in PD in diabetes patients is significantly associated with a decrease in the risk of PD.

Pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus: a retrospective cohort analysis

BackgroundWhether pioglitazone may affect breast cancer risk in female diabetes patients is not conclusive and has not been investigated in the Asian populations.MethodsThe reimbursement database of Taiwan’s National Health Insurance was used to enroll an unmatched cohort and a propensity score-matched cohort of ever users and never users of pioglitazone in female patients with newly diagnosed type 2 diabetes during 1999–2008. The patients were alive on January 1, 2009 and were followed up for breast cancer incidence until December 31, 2011. Cox regression was used to estimate hazard ratios for ever users and tertiles of cumulative duration of pioglitazone therapy versus never users, and for cumulative duration of pioglitazone therapy treated as a continuous variable. Three models were created for the unmatched cohort and the matched cohort, respectively: 1) without adjustment for covariates; 2) after adjustment for covariates that differed with statistical significance (P-value < 0.05) between ever users and never users; and 3) after adjustment for all covariates.ResultsThere were 174,233 never users and 6926 ever users in the unmatched cohort; and 6926 never users and 6926 ever users in the matched cohort. After a median follow-up of 2.8 years, the numbers of incident breast cancer were 1044 in never users and 35 in ever users in the unmatched cohort and were 41 and 35, respectively, in the matched cohort. Hazard ratios suggested a null association between pioglitazone and breast cancer in all three models in either the unmatched cohort or the matched cohort. The overall hazard ratio after adjustment for all covariates was 0.758 (95% confidence interval: 0.539–1.065) in the unmatched cohort and was 0.824 (95% confidence interval: 0.524–1.296) in the matched cohort. None of the hazard ratios for the tertiles of cumulative duration of pioglitazone therapy and for the cumulative duration being treated as a continuous variable were statistically significant.ConclusionsThis study suggests a null association between pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus. However, because of the small breast cancer cases and the limited follow-up time, further studies are warranted to confirm our findings.

Pioglitazone and Risk of Chronic Obstructive Pulmonary Disease in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

BackgroundPioglitazone’s effect on chronic obstructive pulmonary disease (COPD) has rarely been studied.PurposeThis retrospective observational study investigated whether the use of pioglitazone would affect the risk of COPD in patients with type 2 diabetes mellitus.Patients and MethodsThe Taiwan’s National Health Insurance database was used to enroll 9487 matched pairs of ever users and never users of pioglitazone based on propensity score from a cohort of 350,536 patients. The enrolled patients had a new diagnosis of type 2 diabetes mellitus between 1999 and 2008 and were not having a diagnosis of COPD before January 1, 2009. They were then followed up for COPD, starting from January 1, 2009 until December 31, 2011. Diagnosis of COPD was based on the codes of 491 for chronic bronchitis and 492 for emphysema based on the International Classification of Diseases, Ninth Revision, Clinical Modification. Cox regression was used to estimate hazard ratios. The interactions between pioglitazone and COPD risk factors including pneumonia, pulmonary tuberculosis and tobacco abuse were also investigated.ResultsIn 9487 never users and 9487 ever users of pioglitazone, the case numbers of incident COPD were 359 and 295, respectively. The respective incidence rates of COPD were 1484.73 and 1167.61 per 100,000 person-years. The overall hazard ratio (95% confidence interval) for COPD that compared ever to never users was 0.778 (0.667–0.908). The hazard ratios for the tertiles of cumulative duration of pioglitazone therapy (cutoffs: <11.0, 11.0–19.6 and >19.6 months) to never users were 0.904 (0.729–1.121), 0.727 (0.578–0.914) and 0.715 (0.570–0.896), respectively. No interactions between pioglitazone and COPD risk factors including pneumonia, pulmonary tuberculosis and tobacco abuse were noted.ConclusionPioglitazone use is associated with a significantly lower risk of COPD.

Pioglitazone and Prostate Cancer Risk in Taiwanese Male Patients with Type 2 Diabetes: A Retrospective Cohort Study.

This study investigated prostate cancer risk associated with pioglitazone use. The Taiwan's National Health Insurance database was used to create a propensity score-matched cohort of male patients with type 2 diabetes mellitus newly diagnosed in 1999-2005 and aged ≥25 years at baseline. The matched cohort included 20437 ever users and 20437 never users of pioglitazone. The patients were followed up for the incidence of prostate cancer until December 31, 2011. Hazard ratios (HRs) were created from Cox regression weighted on propensity score. Prostate cancer was diagnosed in 121 ever users of pioglitazone (incidence: 175.84 per 100,000 person-years) and 143 never users of pioglitazone (incidence: 216.66 per 100,000 person-years). When ever users were compared to never users of pioglitazone, the HR was 0.815 (95% confidence interval [CI], 0.639-1.039; p=0.0987). When ever users were categorized into tertiles of cumulative duration of pioglitazone therapy (<6.83, 6.83-20.23, and >20.23 months), the HRs were 1.044 (95% CI, 0.741-1.471), 0.975 (95% CI, 0.690-1.377) and 0.539 (95% CI, 0.374-0.778), respectively. For the tertiles of cumulative dose of <5,040, 5,040-15,330, and >15,330 mg, the HRs were 1.008 (95% CI, 0.710-1.429), 1.090 (95% CI, 0.785-1.515) and 0.484 (95% CI, 0.330-0.711), respectively. A significantly lower risk associated with pioglitazone use could only be seen in patients aged <65 years (HR, 0.578; 95% CI, 0.360-0.927) but not in patients aged ≥65 years. A significantly lower risk of prostate cancer is observed after a cumulative duration of pioglitazone therapy for >20.23 months or a cumulative dose of >15,330 mg. The risk reduction is mainly observed in patients aged <65 years.

Type 2 Diabetic Sepsis Patients Have a Lower Mortality Rate in Pioglitazone Use: A Nationwide 15-Year Propensity Score Matching Observational Study in Taiwan.

Background Pioglitazone use via the PPARγ agonist in sepsis patients is inconclusive. It was based on a great number of animal studies. However, except for information from animal studies, there are merely any data of human studies for reference. Methods This study was conducted by a unique database including 1.6 million diabetic patients. From 1999 to 2013, a total of 145,327 type 2 diabetic patients, first admitted for sepsis, were enrolled. Propensity score matching was conducted in a 1 : 5 ratio between pioglitazone users and nonusers. Multivariate logistic regression was conducted to evaluate the adjusted odds ratios (aORs) of hospital mortality in pioglitazone users. Further stratification analysis was done and Kaplan–Meier plot was used. Results A total of 9,310 sepsis pioglitazone users (defined as “ever” use of pioglitazone in any dose within 3 months prior to the first admission for sepsis) and 46,550 matched nonusers were retrieved, respectively. In the multivariate logistic regression model, the cohort of pioglitazone users (9,310) had a decreased aOR of 0.95 (95% CI, 0.89–1.02) of sepsis mortality. Further stratification analysis demonstrated that “chronic pioglitazone users” (defined as “at least” 4-week drug use within 3 months) (3,399) were more associated with significant aOR of 0.80 (95% CI, 0.72–0.89) in reducing sepsis mortality. Conclusions This first human cohort study demonstrated the potential protective effect of chronic pioglitazone use in type 2 diabetic sepsis patients.

POS-365 PIOGLITAZONE REDUCES MORTALITY AND ADVERSE EVENTS IN TYPE 2 DIABETES MELLITUS PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE: NATIONAL COHORT STUDY

Pioglitazone is a thiazolidinedione that can improve peripheral insulin sensitivity and reduce hepatic gluconeogenesis. However, in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD), pioglitazone has been overlooked. The study compared the all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and new-onset of end stage renal disease (ESRD) in type 2 DM patients with advanced chronic kidney disease between pioglitazone users and dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) users. DM patients older than 20 years old with advanced CKD between 2006 and 2016 were identified from the Taiwan’s National Health Insurance Research Database, and were further divided into two groups according to whether they received pioglitazone (pioglitazone group) or DPP4-inhibitors (Comparison group) in the following three months after the advanced CKD date. Propensity score stabilize weighting (PSSW) was used to balance the baseline characteristics between the two groups. The pioglitazone group (n = 2121) exhibited a lower rate (per person-years) of all-cause mortality (12.4% vs. 13.4%, HR: 0.87, 95% CI: 0.81–0.94), MACCEs-related mortality (4.6% vs. 4.7%, HR: 0.87, 95% CI: 0.77–0.98), infection-related mortality (7.5% vs. 8.1%, HR: 0.87, 95% CI: 0.77–0.98), and a marginally lower risk of MACCEs (10.9% vs. 12.4%, HR: 0.92, 95% CI: 0.85–1.00) compared with the comparison group (n =15325). The risk of new-onset ESRD requiring dialysis did not differ between the two groups. This study revealed that pioglitazone can safely reduce several adverse outcomes in DM patients with advanced CKD.

Thiazolidinediones were associated with higher risk of cardiovascular events in patients with type 2 diabetes and cirrhosis.

Type 2 diabetes mellitus (T2DM) management in patients with cirrhosis is complicated. No clinical trials have investigated appropriate antidiabetic drug use in these patients. This study compared the risks of all-cause mortality, major adverse cardiovascular events (MACE) and hepatic outcomes between patients with T2DM and cirrhosis using and not using thiazolidinedione (TZD). We selected 1,705 propensity score-matched TZD users and nonusers from a Taiwan National Health Insurance Research Database cohort of T2DM patients with compensated cirrhosis between January 1, 2000, and December 31, 2012 and followed them until December 31, 2013. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risks of investigated outcomes for TZD users. MACE incidence rates during follow-up were 2.14 and 1.30 per 100 patient-years for TZD users and nonusers, respectively (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI], 1.32-2.19). On the basis of TZD use, the aHRs (95% CIs) for stroke, ischemic heart disease and heart failure were 1.81 (1.28-2.55), 1.59 (1.03-2.44) and 2.09 (1.22-3.60) respectively. Compared with TZD nonusers, rosiglitazone users had significantly higher aHR [1.67 (1.26-2.20)] and pioglitazone users had no significant difference of aHR [1.12 (0.90-1.64)]. All-cause mortality, hepatocellular carcinoma, decompensated cirrhosis and hepatic failure risks did not differ significantly between TZD users and nonusers. Compared with nonuser, TZD users demonstrated significantly higher MACE risks. Therefore, the risks of cardiovascular complications should be considered when prescribing TZDs to patients with T2DM and cirrhosis.

Pioglitazone Is Associated with Lower Major Adverse Cardiovascular and Cerebrovascular Events than DPP4-Inhibitors in Diabetic Patients with End-Stage Renal Disease: A Taiwan Nationwide Cohort Study, 2006–2016

While pioglitazone reduces insulin resistance and hepatic gluconeogenesis effectively in patients with type 2 diabetes mellitus (T2DM), these benefits remained controversial in patients with end stage renal disease (ESRD). We compared major adverse cardiac cerebrovascular events (MACCEs) and mortality (overall, infection-related, and MACCE-related) of pioglitazone to that of dipeptidyl peptidase 4 inhibitors (DPP4-inhibitors) in patients with T2DM and ESRD. From Taiwan’s national health insurance research database (NHIRD), 647 pioglitazone users and 6080 DPP4-inhibitors users between 1 April 2006 and 31 December 2016 were followed from the 91th date after the ESRD certification until the study outcomes, independently; withdraw from the NHI program, death, or 31 December 2017, whichever came first. After weighting, risks of MACCEs (10.48% vs. 12.62% per person-years, hazard ratio (HR): 0.85, 95% (CI): 0.729–0.985) and all-cause mortality (12.86% vs. 13.22% per person-years, (HR): 0.88, 95% (CI): 0.771–0.995) are significantly lower in pioglitazone group. Subgroup analysis found lower MACCEs risk in the pioglitazone users without insulin therapy (6.44% vs. 10.04% (HR): 0.59, 95% (CI): 0.42–0.82) and lower MACCEs related death (2.76% vs. 3.84% (HR): 0.61, 95% (CI): 0.40–0.95) in the pioglitazone group with dyslipidemia, when comparing with DPP4-inhibitors users. Pioglitazone is associated with lower all-cause mortality and MACCEs in diabetic patients with ESRD, compared to DPP4-inhibitors. These benefits were even more significant in the non-insulin users and patients with dyslipidemia.

The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: real-world evidence on thiazolidinedione safety

BackgroundThe low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA).MethodsWe conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999–2012) and a commercial health insurance plan (Optum Clinformatics | 2000–2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset.ResultsThe adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75–1.10) in Medicaid and 0.88 (0.61–1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54–0.93] and 1.16 [0.89–1.52] in men and women respectively, interaction term p-value = 0.01).ConclusionsRosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.

Pioglitazone and PPAR-\u03b3 modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study

Background and aimPeroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown.MethodsBetween 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p < 0.05 and p < 0.1 for clinical outcomes and interaction of subgroup analyses, respectively.ResultsThere were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84–0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068).ConclusionsThe current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments.

Pioglitazone Exposure Reduced the Risk of All-Cause Mortality in Insulin-Treated Patients with Type 2 Diabetes Mellitus.

The long-term safety and benefit of pioglitazone use in combination with insulin are still uncertain. This study compared the risks of all-cause mortality and major cardiovascular (CV) events between pioglitazone users and nonusers receiving insulin therapy. We conducted a 13-year retrospective cohort study by using data from the population-based National Health Insurance Research Database in Taiwan. A total of 20 376 patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy were enrolled during 2000 to 2012. Overall, the incidence rates of all-cause mortality and CV events were compared between 2579 pioglitazone users and 2579 matched nonusers. After adjustment for age, sex, comorbidities, Diabetes Complications Severity Index scores, and drugs used, mortality rates were 30.26 and 15.02 per 1000 person-years for pioglitazone nonusers and users, respectively. The adjusted hazard ratio (aHR) of mortality was 0.47 (95% confidence interval [CI]: 0.38-0.58, P < 0.001) for pioglitazone users compared with nonusers. The aHRs of CV and non-CV deaths were 0.78 (95% CI: 0.51-1.19) and 0.50 (95% CI: 0.38-0.66), respectively. The aHRs of hospitalized coronary artery disease, hospitalized stroke, and incident heart failure were not significantly different between pioglitazone users and nonusers. This nationwide cohort study demonstrated that pioglitazone use reduced the risks of all-cause mortality and non-CV death for patients with T2DM undergoing insulin therapy.

A retrospective study to assess the risk of bladder cancer in type-2 diabetic patients treated with pioglitazone.

Introduction:Pioglitazone has been a cornerstone of oral hypoglycemic therapy. Concerns have been raised about its association with urinary bladder cancer. Considering the wide usage of this drug, concrete and multiple population-based studies are needed to establish the safety of this drug. The present retrospective study is aimed to assess the association of pioglitazone with urinary bladder cancer.Materials and Methods:Clinical records of 4170 patients (2085 pioglitazone users and similar number of nonpioglitazone users) attending the diabetes clinic at a tertiary level teaching hospital were accessed, and the patients were subjected to symptom-directed questionnaire, urine examination, and cystoscopy and bladder biopsy (whenever clinically indicated). The risk of bladder cancer was also assessed with respect to cumulative dose and duration of pioglitazone.Results:We did not observe any increased risk of bladder malignancy with pioglitazone exposure; furthermore, there was no association with cumulative dose and duration of pioglitazone therapy. Pioglitazone was found to be effective and safe in managing glycemic control in diabetic patients.

Post-authorisation Safety Study of Pioglitazone Use and Safety Endpoints of Interest in Denmark After Direct Healthcare Professional Communication.

IntroductionA Direct Healthcare Professional Communication (DHPC) sent in Denmark on 11 August 2011 provided information on new pioglitazone labelling and guidance on monitoring treatment effectiveness. We describe pioglitazone use in Denmark after the DHPC, estimate the incidence of heart failure (HF), quantify pioglitazone cessation following a diagnosis of bladder cancer (BC) or uninvestigated macroscopic haematuria, and describe glycated haemoglobin (HbA1c) values.MethodsThis was a cohort study. From Danish population-based registries, cohorts of type 2 diabetes mellitus incident or prevalent users of pioglitazone or insulin in 2011–2015 were created. Patient characteristics, treatment patterns, laboratory results (available for a regional subset of the population), and incidence rates of HF and BC were estimated.ResultsThere were 80 pioglitazone and 17,699 insulin incident users, 140 pioglitazone and 13,183 insulin prevalent users. There were no new BC cases among incident pioglitazone users, and < 5 new BC cases among prevalent pioglitazone users. Pioglitazone was rarely the first-line treatment. History of haematuria was documented in < 5 incident and 11 prevalent pioglitazone users. During follow-up, there were < 5 HF cases among 77 incident pioglitazone users and < 5 among 133 prevalent pioglitazone users without a history of HF. Median HbA1c at index date was 7.8% and 8.8% in incident pioglitazone and insulin cohorts, and 7.5% and 7.6% in prevalent pioglitazone and insulin cohorts, respectively. During follow-up of up to 4.4 years, 28.8% incident and 20.7% prevalent pioglitazone users discontinued pioglitazone.ConclusionsNumbers of pioglitazone users in Denmark were low and decreased over time. Risks of BC or HF were low and risk estimates imprecise.

DM2 ADHERENCE TO DPP-4 INHIBITORS VERSUS PIOGLITAZONE IN TYPE 2 DIABETES PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE CLAIMS DATABASE ANALYSIS

The objective of the study was to compare adherence and persistence among patients with Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) treated with Dipeptidyl Peptidase-4 (DPP-4) inhibitor versus pioglitazone. This retrospective cohort study used Truven MarketScan® administrative claims databases from 2009-2015. One-year adherence for patients with T2DM and non-dialysis CKD who initiated therapy with either a DPP-4 inhibitor or pioglitazone was measured by the Proportion of Days Covered (PDC) following an initial dispensing and PDC ≥ 0.80 was coded as adherent. Persistence was calculated as the number of days between the first dispensing and the beginning of a gap of two times the days supply or the end of the last days supply or 365 days, whichever came first. Multivariate logistic regression and cox-proportional hazard models were used to estimate confounder-adjusted differences between the groups for adherence and persistence, respectively. The final cohort included 9,019 patients (DPP-inhibitor: 7002; pioglitazone: 2017). In the adjusted analysis, DPP-4 inhibitor users demonstrated a 1.41 (95% Confidence Interval (C.I.) 1.25-1.59) higher odds of being adherent compared to pioglitazone users. The adjusted hazard ratio for persistence differed by index year. Relative to 2010, persistence with pioglitazone decreased in 2011/2012 and then increased in 2013/2014. The DPP-4 inhibitors first had lower (2010: 0.78 (95% C.I. 0.70- 0.87), 2011/2012: 0.60 (95% C.I. 0.54- 0.66)), and then similar (2013/2014: 1.03 (95% C.I. 0.88- 1.19)) hazards of non-persistence compared to pioglitazone. Among patients with T2DM and non-dialysis CKD, the use of DPP-4 inhibitors was associated with better adherence compared to pioglitazone. Safety warnings in 2011 and approval of generic products in 2012 may have impacted pioglitazone persistence. This inconsistent results for persistence with pioglitazone warrant further investigation.

Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis.

Background: The beneficial effect of pioglitazone on dementia requires confirmation. Methods: The database of Taiwan’s National Health Insurance was used to enroll a propensity score-matched-pair cohort of patients who had ever used pioglitazone and patients who had never used pioglitazone from Taiwanese patients with newly diagnosed diabetes mellitus during 1999–2008. The patients were to be alive on 1 January 2009 and were followed up for dementia until 31 December 2011. Hazard ratios were estimated using the Cox proportional hazards model. Results: There were 11,011 never users and 11,011 ever users of pioglitazone, with respective numbers of incident dementia of 123 and 91. The overall hazard ratio was 0.716 (95% confidence interval: 0.545–0.940) for ever users versus never users. The hazard ratios for the first (<11.0 months), second (11.0–19.6 months) and third (>19.6 months) tertiles of cumulative duration were 0.806 (0.544–1.193), 0.654 (0.430–0.994) and 0.694 (0.469–1.026), respectively. When cumulative duration was treated as a continuous variable, the hazard ratio was 0.987 (0.976–0.998). In subgroup analyses, the beneficial effect was mainly observed in patients who had not been treated with metformin. Among metformin ever users, the hazard ratio for dementia for pioglitazone ever users versus never users was 0.802 (0.580–1.109); and was 0.494 (0.284–0.857) among never users of metformin. No interaction between pioglitazone and major risk factors of dementia (i.e., stroke, hypoglycemia, head injury and Parkinson’s disease) was observed. Conclusions: Pioglitazone use is associated with a lower risk of dementia, especially when it is used in never users of metformin and has been used for more than 20 months.

PSY26 - Real-World Prescription Patterns and Comorbidity Burdens Among Adults with Nonalcoholic Fatty Liver Disease

Little research to date has examined the drug utilization pattern among patients with nonalcoholic fatty liver disease (NAFLD). The most recent diagnosis and management guidelines for NAFLD published in 2012 recommended pioglitazone as the effective treatment. In this study, we aim to investigate the real-world drug utilization pattern and comorbidity burden among patients with NAFLD from 2012 to 2015. A retrospective observational study design was employed using the Truven Health MarketScan Commercial Database. Inclusion criteria were: 1) non-elderly patients (age ≥18-<65) who received at least one inpatient or at least two separate outpatient diagnoses of NAFLD (ICD-9: 571.8) between 1/1/2011 and 12/31/2015; 2) available insurance enrollment data for a period of 6-month before and 12-month after the index service date. Patients were excluded if they had one or more claim(s) for type 1 diabetes, chronic hepatitis, alcohol liver diseases, and gestational diabetes. Medications were examined by outpatient prescription claims. The prevalence of each medication was calculated as the number of study subjects taking the specific medication divided by the total number of eligible patients. In the overall study population (N= 76,018) diagnosed with NAFLD, the mean[±SD] age of the patients was 48.4[±10.5] years; 46.8% were male, with a mean[±SD] Charlson comorbidity index score of 1.3[±0.8], 16.9% had type 2 diabetes (T2DM) and 21.2% had lipid metabolism disorders. The proportion of pioglitazone users was 6.2% among patients with co-occurring NAFLD and T2DM, which was six times higher than that of NAFLD patients without T2DM. Compared to the low proportion of pioglitazone uptake among study subjects, metformin was the most frequent prescribed medication among NAFLD patients with T2DM (61.3%) or without T2DM (15.2%). The results showed clinical drug utilization pattern for the management of NAFLD diverged from published guidelines, suggesting promotional programs for pioglitazone use among NAFLD patients are needed.

Pioglitazone use and Parkinson’s disease: a retrospective cohort study in Taiwan

ObjectivesMany researchers have expected pioglitazone to serve as an effective neuroprotective agent against Parkinson’s disease (PD). Therefore, we conducted this cohort study to investigate the association between pioglitazone use and...

Decreased incidence of gout in diabetic patients using pioglitazone.

The incidence and prevalence of gout are increasing, but the management is poor. Considering the increased prevalence of gout in the diabetic population, this study evaluated the effects of pioglitazone, an insulin resistance inhibitor, on the incidence of gout in the diabetic population. We used data from the National Health Insurance program in Taiwan. The pioglitazone cohort contained 30 100 patients and each patient was age and sex matched with three non-pioglitazone users who were randomly selected from the diabetic population. Cox proportional hazards regression analysis was conducted to estimate the effects of pioglitazone on the incidence of gout in the diabetic population. The incidence of gout was significantly lower in pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR) 0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)] pioglitazone users than in non-pioglitazone users. An analysis of three age groups (<40, 40-59 and ⩾60 years) revealed that the HRs of both the 40-59 years [aHR 0.78 (95% CI 0.73, 0.83)] and the ⩾60 years [aHR 0.85 (95% CI 0.80, 0.91)] age groups were significantly lower among pioglitazone users than non-pioglitazone users. Compared with the non-pioglitazone users, the incidence of gout in the diabetic population using pioglitazone was less.