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Background: Most existing risk equations for predicting/stratifying individual diabetic kidney disease (DKD) risks were developed using relatively dated data from selective and homogeneous trial populations comprising predominately Caucasian type 2 diabetes (T2D) patients. We seek to adapt risk equations for prediction of DKD progression (microalbuminuria, macroalbuminuria, and renal failure) using empiric data from a real-world population with T2D in Taiwan. Methods: Risk equations from three well-known simulation models: UKPDS-OM2, RECODe, and CHIME models, were adapted. Discrimination and calibration were determined using the area under the receiver operating characteristic curve (AUROC), a calibration plot (slope and intercept), and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was performed for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of risk equations to address risk variations among patients. Results: The RECODe equations for microalbuminuria and macroalbuminuria showed moderate discrimination (AUROC: 0.62 and 0.76) but underestimated the event risks (calibration slope > 1). The CHIME equation had the best discrimination for renal failure (AUROCs from CHIME, UKPDS-OM2 and RECODe: 0.77, 0.60 and 0.64, respectively). All three equations overestimated renal failure risk (calibration slope < 1). After rigorous updating, the calibration slope/intercept of the recalibrated RECODe for predicting microalbuminuria (0.87/0.0459) and macroalbuminuria (1.10/0.0004) risks as well as the recalibrated CHIME equation for predicting renal failure risk (0.95/-0.0014) were improved. Conclusions: Risk equations for prediction of DKD progression in real-world Taiwanese T2D patients were established, which can be incorporated into a multi-state simulation model to project and differentiate individual DKD risks for supporting timely interventions and health economic research. [ABSTRACT FROM AUTHOR]

Background: To assess the association of cirrhosis and hepatocellular carcinoma (HCC) with the use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) versus long‐acting insulins (LAIs), which are the two commonly prescribed injectable glucose‐lowering agents (GLAs) for patients with type 2 diabetes (T2D) after the failure of multiple oral GLAs. Methods: We emulated a target trial using the nationwide data of a Taiwanese cohort with T2D. Incident new users of GLP‐1RAs and LAIs during 2013–2018 were identified, and propensity score (PS) matching was applied to ensure between‐group comparability in baseline patient characteristics. The primary outcome was the composite liver disease including cirrhosis or HCC. Each patient was followed until the occurrence of a study outcome, death, or the end of 2019, whichever came first. Subdistribution hazard models were employed to assess the treatment‐outcome association. Sensitivity (e.g., stabilized inverse probability of treatment weighting analysis, time‐dependent analysis), E‐value, and negative control outcome analyses were performed to examine the robustness of study findings. Results: We included 7171 PS‐matched pairs of GLP‐1RA and LAI users with no significant between‐group differences at baseline. Compared with LAIs, the use of GLP‐1RAs was associated with significantly reduced risks of composite liver disease (subdistribution hazard ratio [95% confidence interval]: 0.56 [0.42–0.76]), cirrhosis (0.59 [0.43–0.81]), and HCC (0.47 [0.24–0.93]). Results were consistent across sensitivity analyses and among patients with different baseline characteristics. Conclusion: Among T2D patients who require injectable GLAs, the use of GLP‐1RAs versus LAIs was associated with lower risks of cirrhosis and HCC. [ABSTRACT FROM AUTHOR]

Background: Effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs) on preventing progressive chronic kidney outcomes is uncertain for type 2 diabetes (T2D) patients requiring intensive glycemic control. This study aimed to evaluate comparative effectiveness of GLP-1RA versus LAI therapies on progressive chronic kidney outcomes among patients having poor glycemic control and requiring these injectable glucose-lowering agents (GLAs). Methods: 7279 propensity-score-matched pairs of newly stable GLP-1RA and LAI users in 2013–2018 were identified from Taiwan's National Health Insurance Research Database and followed until death or 12/31/2019 (intention-to-treat). Subdistributional hazard model was utilized to assess the comparative effectiveness on a composite renal outcome (i.e., renal insufficiency [eGFR < 15 mL/min/1.73 m2], dialysis-dependent end-stage renal disease [ESRD], or renal death) and its individual components. Sensitivity analyses with the as-treated scenario, PS weighting, high-dimensional PS techniques, using cardiovascular diseases (CVDs) as positive control outcomes, and interaction testing were performed. Results: In primary analyses, subdistribution hazard ratios (95% CIs) for initiating GLP-1RAs versus LAIs for the composite renal outcome, renal insufficiency, dialysis-dependent ESRD, and renal death were 0.39 (0.30–0.51), 0.43 (0.32–0.57), 0.29 (0.20–0.43), and 0.28 (0.15–0.51), respectively. Sensitivity analysis results were consistent with the primary findings. CVD history and the medication possession ratio of prior oral GLAs possessed modification effects on GLP-1RA-associated kidney outcomes. Conclusion: Using GLP-1RAs versus LAIs was associated with kidney benefits in T2D patients requiring intensive glycemic control and potentially at high risk of kidney progression. GLP-1RAs should be prioritized to patients with CVDs or adherence to prior oral GLAs to maximize kidney benefits. [ABSTRACT FROM AUTHOR]

Incidence rates for diseases are widely used in the field of medical research because they lead to clear and simple physical and clinical interpretations. In this study, we propose an efficient estimation method that incorporates auxiliary subgroup information related to the incidence rate into the estimation of the Cox proportional hazard model. The results show that utilizing the incidence rate information improves the efficiency of the estimation of regression parameters based on the double empirical likelihood method compared to that for conventional models that do not incorporation such information. We show that estimators of regression parameters asymptotically follow a multivariate normal distribution with a variance-covariance matrix that can be consistently estimated. Simulation results indicate that the proposed estimators significantly increase efficiency. Finally, an example of the effects of type 2 diabetes on stroke is applied to demonstrate the proposed method. [ABSTRACT FROM AUTHOR]

Objective: We assessed the effects of sodium glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) in a large real-world Asian cohort with type 2 diabetes (T2D) and performed a systematic review with integrating the present study findings to provide up-to-date evidence from the Asian perspective. Methods: New users of SGLT2is or DPP4is were identified from the Taiwan's National Health Insurance Research Database and followed until 2018. Primary outcomes were hospitalization for heart failure (HHF) and three-point major adverse cardiovascular event (3P-MACE; namely, myocardial infarction [MI], stroke, or cardiovascular death). Other outcomes included all-cause death, chronic kidney disease (CKD), amputation, and hospitalized hypoglycemia. Subdistribution hazard models were employed to assess treatment-associated clinical outcomes. Results: A total of 21,329 SGLT2i and DPP4i propensity-score-matched pairs were analyzed. SGLT2is versus DPP4is showed lower risks of HHF (hazard ratio [95% CI]: 0.52 [0.45–0.59]), 3P-MACE (0.62 [0.55–0.70]), MI (0.63 [0.50–0.79]), stroke (0.60 [0.51–0.70]), all-cause death (0.57 [0.49–0.67]), CKD (0.46 [0.43–0.50]), amputation (0.64 [0.42–0.98]), and hospitalized hypoglycemia (0.54 [0.45–0.64]). Our results were consistent with findings from a systematic review. Conclusion: Among Asian patients with T2D, SGLT2is versus DPP4is showed benefits for several clinical outcomes. More research is warranted to explore the heterogeneous treatment effects of SGLT2is and DPP4is by race/ethnicity. [ABSTRACT FROM AUTHOR]

We developed a three-step matching algorithm to enhance the between-group comparability for comparative drug effect studies involving prevalent new-users of the newer study drug versus older comparator drug(s). The three-step matching scheme is to match on: (1) index date of initiating the newer study drug to align the cohort entry time between study groups, (2) medication possession ratio measures that consider prior exposure to all older comparator drugs, and (3) propensity scores estimated from potential confounders. Our approach is illustrated with a comparative cardiovascular safety study of glucagon-like peptide-1 receptor agonist (GLP-1ra) versus sulfonylurea (SU) in type 2 diabetes patients using Taiwan's National Health Insurance Research Database 2003–2015. 66% of 3195 GLP-1ra users had previously exposed to SU. The between-group comparability was well-achieved after implementing the matching algorithm (i.e., standardized mean difference < 0.2 for all baseline patient characteristics). Compared to SU, the use of GLP-1ra yielded a significantly reduced risk of the primary composite cardiovascular events (hazard ratio [95% confidence interval]: 0.71 [0.54–0.95], p = 0.022). Our matching scheme can enhance the between-group comparability in prevalent new-user cohort designs to minimize time-related bias, improve confounder adjustment, and ensure the reliability and validity of study findings. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To estimate preference‐based measures of health‐related quality of life associated with sociodemographic and clinical characteristics in type 2 diabetes patients. Materials and Methods: Individuals with EuroQol‐5 dimensions‐3 levels data were identified from Taiwan's National Health Interview Survey in 2009 and 2013. Status of diabetes, comorbidities, complications and treatments were ascertained through data linkage to Taiwan's National Health Insurance Research Database. Multivariable ordinary least squares, Tobit and median regression analyses were used to estimate the coefficients that represented independent impacts of patients' characteristics on health‐related quality of life. Results: The mean health utility score for 2,104 participants was 0.838. Being female, aging, divorced/widowed, never worked or underweight, or having a lower monthly household income, injectable glucose‐lowering therapy, comorbid connective tissue disease or depression were associated with lower health utilities. Having an amputation led to the largest reduction by 0.288 in health utilities, followed by debilitating stroke (0.266), heart failure (0.237), other coronary heart disease (0.185), kidney dialysis/transplant (0.148), coronary revascularizations (0.093), transient ischemic attack/stroke (0.078), diabetic neuropathy (0.062), polyneuropathy (0.055) and other neuropathy (0.043). Conclusions: Major vascular complications, connective tissue disease and depression are associated with considerably worse health‐related quality of life. These health utility estimates can facilitate health economic evaluations to determine cost‐effective strategies for diabetes management. [ABSTRACT FROM AUTHOR]

This study assessed the effects of dipeptidyl peptidase‐4 inhibitors (DPP4is) vs. sulfonylureas (SUs) on composite renal, cardiovascular, and hospitalized hypoglycemia outcomes in type 2 diabetes (T2D) patients with advanced chronic kidney disease (CKD) who were underrepresented in previous clinical studies. The National Health Insurance Research Database was utilized. Patients with T2D and advanced CKD (stages 3b‐5) with stable use of DPP4is or SUs were identified during 2011–2015 and followed until death or December 31, 2016. The primary outcome was the composite renal outcome. Secondary outcomes included hospitalized heart failure (HHF), major adverse cardiovascular event (MACE), hospitalized hypoglycemia, and all‐cause death. Subdistribution hazard models were employed to assess treatment effects on clinical outcomes. A total of 1,204 matched pairs of DPP4i and SU users were analyzed. Compared with SUs, DPP4is had no significant difference in the risks of the composite renal outcome, HHF, and three‐point and four‐point MACE (hazard ratios (95% confidence intervals): 1.10 (0.93–1.31), 1.11 (0.95–1.30), 0.97 (0.79–1.19), and 1.08 (0.94–1.24), respectively), but reduced risks of hospitalized hypoglycemia (0.53 (0.43–0.64)) and all‐cause death (0.71 (0.53–0.96)). In conclusion, among patients with T2D and advanced CKD, the use of DPP4is vs. SUs was associated with comparable safety profiles on renal and cardiovascular outcomes, and reduced risks of hospitalized hypoglycemia and all‐cause death. DPP4is may be preferred for patients with T2D and advanced CKD, and the regular monitoring on cardiac function remains crucial among this population who are at a higher risk of HHF. [ABSTRACT FROM AUTHOR]

This study explored heterogeneous treatment effects (HTEs) of the real‐world use of dipeptidyl peptidase‐4 inhibitors (DPP‐4is) vs. sulfonylureas (SUs) on cardiovascular diseases (CVDs) and mortality in patients with type 2 diabetes. Utilizing Taiwan's National Health Insurance Research Database, 19,853 propensity score‐matched pairs of DPP‐4i and SU stable users were identified. Classification and regression tree analyses and Cox models were applied to explore HTEs, according to various patient characteristics, on the composite CVDs, three‐point major adverse cardiovascular event (MACE), and all‐cause mortality. The absolute risk difference (ARD), hazard ratio (HR), and 95% confidence interval (CI) were estimated for comparing treatment effects. CVD history, ischemic stroke, or transient ischemic attack (IS/TIA) history, and age at treatment initiation were significant treatment effect modifiers. Patients with prior IS/TIA but without any other prior CVDs benefited most in reduced risks of composite CVDs from using DPP‐4i vs. SU (ARD −4.31%, 95% CI −7.48% to −1.14%, HR 0.81, 95% CI 0.69 ~ 0.95), followed by those without prior IS/TIA and CVDs and initiated with DPP‐4i at age < 69.3 years (ARD −0.90%, 95% CI −1.47% to −0.32%, HR 0.86, 95% CI 0.77 ~ 0.97). Patients with prior IS/TIA benefited most in reduced risks of three‐point MACE from using DPP‐4i vs. SU (ARD −4.22%, 95% CV −6.66% to −1.78%, HR 0.80, 95% CI 0.69 ~ 0.93), followed by those without prior IS/TIA and initiated with DPP‐4i at age < 69.3 years (ARD −0.68%, 95% CI −1.08% to −0.29%, HR 0.81, 95% CI 0.70 ~ 0.93). Consideration of CVD and IS/TIA histories and age could facilitate individualized diabetes management of using DPP‐4i vs. SU. Future studies are warranted given the hypothesis‐generating nature in this exploratory research. [ABSTRACT FROM AUTHOR]

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan's National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004–2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20–2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51–2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84–0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population. [ABSTRACT FROM AUTHOR]

Background: Head-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. Methods: We conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016–2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every 3 months in the 1-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. Results: A total of 1512 subjects receiving dulaglutide and 1513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: − 1.06%, p < 0.001; liraglutide: − 0.83%, p < 0.001), with a significant between-group difference (− 0.23%, 95% confidence interval − 0.38 to − 0.08%, p < 0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: − 1.14 kg, − 3.08 U/L and − 2.08 mL/min/1.73 m2, p < 0.01; liraglutide: − 1.64 kg, − 3.65 U/L and − 2.33 mL/min/1.73 m2, p < 0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (− 2.47 mmHg, p < 0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. Conclusions: In real-world T2D patients, dulaglutide versus liraglutide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions. [ABSTRACT FROM AUTHOR]

Objective: Developing country-specific unit-cost catalogs is a key area for advancing economic research to improve medical and policy decisions. However, little is known about how health care costs vary by type 2 diabetes (T2D) complications across time in Asian countries. We sought to quantify the economic burden of various T2D complications in Taiwan.Research Design and Methods: A nationwide, population-based, longitudinal study was conducted to analyze 802,429 adults with newly diagnosed T2D identified during 1999-2010 and followed up until death or 31 December 2013. Annual health care costs associated with T2D complications were estimated, with multivariable generalized estimating equation models adjusted for individual characteristics.Results: The mean annual health care cost was $281 and $298 (2017 U.S. dollars) for a male and female, respectively, diagnosed with T2D at age <50 years, with diabetes duration of <5 years, and without comorbidities, antidiabetic treatments, and complications. Depression was the costliest comorbidity, increasing costs by 64-82%. Antidiabetic treatments increased costs by 72-126%. For nonfatal complications, costs increased from 36% (retinopathy) to 202% (stroke) in the event year and from 13% (retinopathy or neuropathy) to 49% (heart failure) in subsequent years. Costs for the five leading costly nonfatal subtype complications increased by 201-599% (end-stage renal disease with dialysis), 37-376% (hemorrhagic/ischemic stroke), and 13-279% (upper-/lower-extremity amputation). For fatal complications, costs increased by 1,784-2,001% and 1,285-1,584% for cardiovascular and other-cause deaths, respectively.Conclusions: The cost estimates from this study are crucial for parameterizing diabetes economic simulation models to quantify the economic impact of clinical outcomes and determine cost-effective interventions. [ABSTRACT FROM AUTHOR]

Background: Current evidence about the cardiovascular safety of glucagon-like peptide-1 receptor agonist (GLP-1ra) possesses limited generalizability to real-world patients with type 2 diabetes (T2D) in usual practice. This study aimed to investigate the comparative cardiovascular safety of GLP-1ra in comparisons with dipeptidyl peptidase-4 inhibitor (DPP-4i), sulfonylurea (SU), and insulin in a real-world population with T2D. Methods: Adults with newly-diagnosed T2D were identified from Taiwan's National Health Insurance Research Database in 2003–2014. A prevalent new-user cohort design was adopted to include a broad representation of real-world T2D patients being treated with GLP-1ra. The between-group comparability of baseline patient characteristics was achieved by matching on (1) initiation time of study drugs, (2) prior exposure to glucose-lowering agents, and (3) diabetes severity and complications, comorbidities, and concomitant cardiovascular medications using propensity scores. The primary outcome was a composite of cardiovascular disease (CVD) events and assessed up to the end of 2015. Cox modeling was employed to assess the association between study drugs and outcomes. Results: A total of 3195 GLP-1ra stable users was identified in 2011-2014. 1893, 1829, and 1367 GLP-1ra stable users were 1:1 matched to DPP-4i, SU and insulin users, respectively. Compared to DPP-4i, SU and insulin, the use of GLP-1ra was associated with a lower risk of composite CVD events [hazard ratio (95% confidence interval) 0.73 (0.57–0.96), 0.76 (0.57–1.00), and 0.81 (0.62–1.07), respectively]. Subgroup analyses revealed that GLP-1ra versus DPP-4i yielded a greater cardiovascular benefit in those without established CVD versus those with established CVD. Conclusions: This comparison study extends the supporting evidence for the cardiovascular safety of GLP-1ra to a broad spectrum of real-world T2D patients using GLP-1ra. [ABSTRACT FROM AUTHOR]

Aims: To compare the effects of initiating insulin as a fourth‐line antidiabetic therapy with the effects of enhancing oral antidiabetic drug (OAD) therapy in patients with type 2 diabetes mellitus (T2DM) with triple OAD therapy failure. Materials and methods: We conducted a nationwide population‐based, retrospective cohort study involving 1022 (without prevalent diabetes‐related complications [PDRCs]) and 2077 (with/without PDRCs) propensity score‐matched pairs of fourth‐line insulin therapy users and enhanced OAD therapy users identified in the period 2004 to 2010. Clinical outcomes including a composite cardiovascular outcome (myocardial infarction, stroke, heart failure or ischaemic heart disease), peripheral vascular disease (PVD), hypoglycaemia and all‐cause mortality were assessed up to 2013. Hypoglycaemia was adjusted in Cox models to consider its potential effect on study outcomes. Results: In a T2DM cohort without PDRCs, fourth‐line insulin therapy was not associated with greater risks of clinical outcomes, except hypoglycaemia (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.02‐2.07), compared with enhanced OAD therapy. Among patients with T2DM with/without PDRCs, fourth‐line insulin therapy was associated with greater risks of the composite cardiovascular outcome (HR 1.23, 95% CI 1.03‐1.46), heart failure (HR 1.59, 95% CI 1.12‐2.25), ischaemic heart disease (HR 1.37, 95% CI 1.09‐1.73), PVD (HR 1.17, 95% CI 1.00‐1.36), hypoglycaemia (HR 1.49, 95% CI 1.20‐1.85) and all‐cause mortality (HR 1.48, 95% CI 1.01‐2.17), but adjustment for hypoglycaemia significantly attenuated the risk of heart failure (HR 1.34, 95% CI 0.92‐1.94), PVD (HR 1.15, 95% CI 0.98‐1.34) and all‐cause mortality (HR 1.30, 95% CI 0.84‐1.99). Conclusions: Initiation of fourth‐line insulin therapy can be considered for patients with T2DM with triple OAD therapy failure, and the importance of awareness and prevention of hypoglycaemia among insulin‐treated patients with T2DM cannot be overstated. [ABSTRACT FROM AUTHOR]

To retrospectively analyze the association of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) with a range of major and non-major fracture events, and explore heterogeneous treatment effect among high-risk patient subgroups. Newly stable SGLT2i or DPP4i users in 2017 were identified in Taiwan's National Health Insurance Research Database and followed up until a fracture occurred, loss of follow-up, death, or December 31, 2018, whichever came first. Outcomes included composite major and non-major fractures and individual components in major fractures. Cox model and restricted mean survival time (RMST) analyses were utilized to assess the treatment effect on fractures. 21,155 propensity-score-matched SGLT2i and DPP4i users were obtained. Over 2 years, the hazard ratio and RMST difference for major fracture with SGLT2i versus DPP4i use were 0.89 (95% CI, 0.80, 1.00) and 1.51 (-0.17, 3.17) days, respectively, and those for non-major fracture with SGLT2i versus DPP4i use were 0.89 (0.81, 0.98) and 2.44 (0.47, 4.37) days, respectively. A 180-day lag time analysis for fracture outcomes showed consistent results with primary findings. A SGLT2is-associated harmful effect on major fractures (but not on non-major fractures) was observed among female patients and those with a diabetes duration of ≥ 8 years, prior fractures, and established osteoporosis. This study adds supporting real-world evidence for SGLT2is-associated bone safety for a wide range of fractures, which promotes the rational use of SGLT2is in routine care and highlights the importance of the close monitoring of patients with high fracture risks to maximize treatment benefits while reducing undesirable effects. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the putative link between dipeptidyl peptidase‐4 inhibitor (DPP‐4i) use and the risk of fracture in patients with type 2 diabetes. Methods: This propensity‐score‐matched population‐based cohort study was performed between 2009 and 2013 on patients with type 2 diabetes who were stable metformin users. A total of 3996 patients with type 2 diabetes used DPP‐4i as a second‐line antidiabetic drug. The same number of matched non‐DPP‐4i users were followed up until fracture occurrence, health insurance policy termination, or the end of 2013. The incidence rates of overall and cause‐specific fractures were estimated based on the Poisson assumption. A multiple Cox proportional hazard model was used to estimate the covariate‐adjusted hazard ratio (HR) and 95% confidence interval (CI) to determine the association between DPP‐4i use and overall and cause‐specific fractures stratified by age and sex. Results: Over a maximum follow‐up period of 5 years, 340 DPP‐4i users and 419 non‐DPP‐4i users were newly diagnosed with fractures, yielding incidence rates of 28.03 and 32.04 per 1000 people per year, respectively. The Cox proportional hazard model revealed that DPP‐4i use significantly reduced the risk of all‐cause fractures and upper extremity fractures, with adjusted HRs of 0.86 (95% CI: 0.74–0.99) and 0.75 (95% CI: 0.59–0.95), respectively. The aforementioned associations of DDP‐4i use with fracture were sustained across sex and age stratifications. Conclusions: The results of this study supported the premise that DPP‐4i usage is associated with a reduced risk of all‐cause fractures and upper extremity fractures in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims Dipeptidyl peptidase 4 inhibitors (DPP4is) are suggested as a second- and third-line antidiabetic treatment for type 2 diabetes. Previous studies assessed only the cardiovascular effects of DPP4is as a second-line treatment, included sulphonylurea as the only comparator, and yielded inconclusive results on the risk of heart failure. The present study therefore evaluated the comparative cardiovascular risks of DPP4is with other second- and third-line antidiabetic drugs. Methods Based on a large nationwide diabetic cohort, 113 051 patients with type 2 diabetes newly on metformin-based dual or triple therapy were identified in 2009-2011 and followed until 2013, or death if this occurred sooner. Primary interest targeted hospitalizations for ischaemic stroke, myocardial infarction and heart failure. Secondary outcomes were hypoglycaemia and all-cause mortality. Cox proportional hazards models were performed to assess time-to-event hazard ratio between propensity score-matched antidiabetic treatment groups. Results DPP4is as a second-line add-on to metformin had a significantly lower stroke risk [hazard ratio (HR) 0.817 (95% confidence interval 0.687, 0.971)] and all-cause mortality [HR 0.825 (0.687, 0.992)] than those for sulphonylurea. DPP4is as a third-line add-on to metformin and sulphonylurea combined dual therapy had a significantly lower risk for stroke [HR 0.826 (0.740, 0.923)] and all-cause mortality [HR 0.784 (0.701, 0.878)] than those for acarbose, and significantly lower risks for stroke [HR 0.653 (0.542, 0.786)], heart failure [HR 0.721 (0.568, 0.917)] and all-cause mortality [HR 0.689 (0.594, 0.703)] than those for meglitinide. Conclusions DPP4is as a second- or third-line add-on treatment provided cardiovascular benefits and posed no increased risks for heart failure, hypoglycaemia or death. [ABSTRACT FROM AUTHOR]

Background: Care of the elderly with diabetes is more complicated than that for other age groups. The elderly and/or those with multiple comorbidities are often excluded from randomized controlled trials of treatments for diabetes. The heterogeneity of health status of the elderly also increases the difficulty in diabetes care; therefore, diabetes care for the elderly should be individualized. Motivated patients educated about diabetes benefit the most from collaborating with a multidisciplinary patient-care team. A pharmacist is an important team member by serving as an educator, coach, healthcare manager, and pharmaceutical care provider.Objective: To evaluate the effects of pharmaceutical care on glycemic control of ambulatory elderly patients with type 2 diabetes.Setting: A 421-bed district hospital in Nantou City, Taiwan.Method: We conducted a randomized controlled clinical trial involving 100 patients with type 2 diabetes with poor glycemic control (HbA1c levels of ≥9.0 %) aged ≥65 years over 6 months. Participants were randomly assigned to a standard-care (control, n = 50) or pharmaceutical-care (intervention, n = 50) group. Pharmaceutical care was provided by a certified diabetes-educator pharmacist who identified and resolved drug-related problems and established a procedure for consultations pertaining to medication. The Mann–Whitney test was used to evaluate nonparametric quantitative data. Statistical significance was defined as P < 0.05.Main Outcome Measure: The change in the mean HbA1c level from the baseline to the next level within 6 months after recruiting.Results: Nonparametric data (Mann–Whitney test) showed that the mean HbA1c level significantly decreased (0.83 %) after 6 months for the intervention group compared with an increase of 0.43 % for the control group (P ≤ 0.001). Medical expenses between groups did not significantly differ (−624.06 vs. −418.7, P = 0.767). There was no significant difference in hospitalization rates between groups.Conclusion: The pharmacist intervention program provided pharmaceutical services that improved long-term, safe control of blood sugar levels for ambulatory elderly patients with diabetes and did not increase medical expenses. [ABSTRACT FROM AUTHOR]

No single gold standard of comorbidity measure has been identified, and the performance of comorbidity indices vary according to the outcome of interest. The authors compared the Charlson Comorbidity Index, Elixhauser Index (EI), Chronic Disease Score (CDS), and Health-related Quality of Life Comorbidity Index (HRQL-CI) in predicting health care-related behaviors (physicians' concordance with diabetes care standards and patients' oral antidiabetic drug [OAD] adherence) and outcomes (health care utilization and expenditures) among Medicaid enrollees with type 2 diabetes. A total of 9832 diabetes patients who used OAD were identified using data from the MarketScan Medicaid database from 2003 to 2007. Predictive performance of the comorbidity index was assessed using multiple regression models controlling for patient demographics, diabetes severity, and baseline health care characteristics. Among the 4 indices, the CDS was best at predicting physician's concordance with care standards. The CDS and HRQL-CI mental index performed better than other indices as predictors of medication adherence. The EI was best at predicting health care utilization and expenditures. These results suggest that, for these low-income diabetes patients, the CDS and HRQL-CI mental index were relatively better risk-adjustment tools for health care-related behavior data evaluation and the EI was the first choice for health care utilization and expenditures data. ( Population Health Management 2012;15:220-229) [ABSTRACT FROM AUTHOR]

Background Studies from other countries indicate that utilization patterns of antidiabetic drugs change significantly after the introduction of newer classes of antidiabetic drugs (e.g. dipeptidyl peptidase-4 inhibitors [DPP-4i]). Evidence on recent trends regarding antidiabetic drug use in Taiwan is lacking, especially for times after the introduction of newer classes of drugs (e.g. DPP-4i). Therefore, the aim of the present study was to assess: (i) recent trends in the use and spending on antidiabetic drugs; (ii) changes in utilization patterns after introduction of newer classes of antidiabetic drugs; and (iii) factors associated with the choice of newer versus older classes of antidiabetic drugs. Methods Cases of type 2 diabetes were derived from Taiwan's National Health Insurance Research Database. Antidiabetic drug use was measured in terms of total quantity of drug exposure and healthcare spending in each calendar year from 2008 to 2103. Multiple logistic regression analysis was used to assess factors associated with drug choice. Results The use of and healthcare spending on DPP-4i increased significantly from 2008 to 2013, whereas healthcare spending on sulfonylureas decreased. For monotherapy, sulfonylureas were the most common alternatives to metformin, whereas in dual and triple antidiabetic therapies, a DPP-4i was the most common alternative to initial regimens. The use of a DPP-4i was positively associated with the use of beta-blockers, angiotensin II-converting enzyme inhibitors and/or angiotensin receptor blockers, and lipid-lowering agents, but negatively correlated with age, hypertension, severity of diabetes complications, and the use of diuretics and calcium channel blockers. Conclusions With growing spending on newer antidiabetic drugs, future research on the comparative cost-effectiveness and safety of antidiabetic drugs is anticipated. [ABSTRACT FROM AUTHOR]

To evaluate the cost-effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs) in patients with type 2 diabetes (T2D) using real-world data. A Markov model was utilized to estimate healthcare costs (US$) and quality-adjusted life-years (QALYs) of receiving treatments over 10 years from the healthcare sector perspective. Model inputs were derived from the analyses of Taiwan's National Health Insurance Research Database or published literature on Taiwanese T2D populations. Base-case analysis was performed for the overall study cohort and subgroup analyses were stratified by the presence or absence of established cardiovascular diseases (CVDs) or chronic kidney diseases (CKDs). Overall, using GLP-1RAs versus LAIs cost $6,053 per QALY gained. Results were robust across sensitivity and scenario analyses. Among patients with established CVDs and CKDs, GLP-1RA versus LAI therapy saved $673 (cost-saving) and cost $1,675 per QALY gained, respectively. Among patients without established CVDs and CKDs, GLP-1RA versus LAI therapy cost $9,093 and $7,659 per QALY gained, respectively. Using GLP-1RAs versus LAIs for T2D patients represented good economic value in real-world practice. Pronounced economic benefits of GLP-1RA therapy among those with prior CVDs or CKDs support rational treatment decisions and optimal healthcare resource allocation for these patients. [ABSTRACT FROM AUTHOR]

Abstract: Background and Objective: Although the predictive ability of the Charlson Index, Elixhauser Index (EI), Chronic Disease Score (CDS), and Health-related Quality of Life Comorbidity Index (HRQL-CI) for health care outcomes has been assessed individually, little research has compared the discriminative performance of these indices directly in a single study. The current study compared these indices in discriminating among type 2 diabetes patients varying in demographics and health care outcomes characteristics. Study Design: There were 9832 Medicaid patients with type 2 diabetes from 8 states evaluated. Endpoints included demographics (age, race), health care behaviors (physician''s diabetes care standard adherence, patient''s medication adherence), and health care utilization and expenditures. Discriminative power of comorbidity indices was determined by c-statistics from logistic regression, the shape of receiver operator characteristic curve, and area under the curve. Results: The CDS demonstrated the best ability in discriminating between age subgroups (c=0.61) and patients who were or were not adherent to their medication (c=0.56). The CDS and HRQL-CI mental index performed similarly in discriminating based on diabetes care standard adherence (c=0.60). The EI had the best discrimination for health care utilization and costs, while HRQL-CI physical index performed similarly to EI in predicting hospitalization admission (c=0.62), and the HRQL-CI mental index performed similarly to the EI in predicting outpatient visits (c=0.74). Conclusions: The CDS was found to be the best metric for differentiating among patients varying in demographics, physician''s diabetes care standard adherence, and patient''s medication adherence, while the EI should be the first choice to identify patients at risk of high medical resource use. [Copyright &y& Elsevier]

This is the first large longitudinal cohort study to investigate the putative association of severe joint pain (SJP) with dipeptidyl peptidase-4 inhibitor (DPP4i) use in patients with type 2 diabetes. The propensity score-matched population-based cohort study was performed between 2009 and 2013 in a group of type 2 diabetes patients with stable metformin use. In total, 4743 patients with type 2 diabetes used a DPP4i as the second-line antidiabetic drug (ie, DPP4i users), and the same number of matched non-DPP4i users was selected. The 2 study groups were followed up until SJP diagnosis (International Classification of Diseases, Ninth Reversion, Clinical Modification code 719.4), health insurance policy termination, or the end of 2013. The incidence rate of SJP was estimated under the Poisson assumption. Multiple Cox proportional hazard model was used to estimate the covariate-adjusted hazard ratio and 95% CI of SJP in association with DPP4i use. Over a maximum follow-up of 5 years, 679 DPP4i users and 767 non-DPP4i users were newly diagnosed with SJP, representing incidence rates of 47.20 and 50.66 per 1000 person-years, respectively. Cox proportional hazard model indicated that DPP4i use slightly but nonsignificantly reduced the risk of SJP (adjusted hazard ratio: 0.92 [95% CI: 0.83-1.02]). Such null results were also observed among all age and sex stratifications and in a sensitivity analysis using all nonspecific arthropathies as the study endpoint. This study provides no support for the putative risk of SJP related to DPP4i use in type 2 diabetes patients during a maximum follow-up of 5 years. [ABSTRACT FROM AUTHOR]

Aim: To assess the relationship between acarbose and hepatotoxicity, cardiovascular disease (CVD), and mortality among type 2 diabetes (T2D) patients with end-stage renal disease (ESRD).Methods: 32,531 T2D patients with ESRD were identified from Taiwan's National Health Insurance Research Database in 2000~∼2012 and followed up until 2013. 19.3% of subjects were newly initiated with acarbose during the follow-up. The use of acarbose was quantified as the numbers of the 30-day drug's supplies and dosages (measured by defined daily doses; DDDs), respectively. Time-varying Cox models were applied to evaluate the association of acarbose use with hepatic, cardiovascular and mortality outcomes, with adjustment for patients' demographics, comorbidities, diabetes severity, and co-medications.Results: For each 30-day supply increase in acarbose exposure, the risks of hepatic injury, composite CVD events, and all-cause mortality were significantly lowered by 9% (95% confidence interval: 6-12%), 7% (6-7%) and 7% (7-8%), respectively, while for each 30-day DDD increase in acarbose exposure, the risks for three aforementioned outcomes were significantly reduced by 45% (33-54%), 33% (29-36%) and 35% (32-39%), respectively. In subgroup analyses, the favorable study outcomes of acarbose use were more apparent among patients with more severe diabetes, a longer diabetes duration, or absence of established CVD at baseline.Conclusion: Acarbose used in real-world T2D patients with ESRD may have hepatic and cardiovascular safety. [ABSTRACT FROM AUTHOR]