Statin therapy is beneficial in reducing cardiovascular events and mortalities in patients with atherosclerotic cardiovascular diseases. Yet, there have been concerns of increased risk of diabetes with statin use. This study was aimed to evaluate the association between statins and new onset diabetes mellitus (NODM) in patients with ischemic heart disease (IHD) utilizing the Korean Health Insurance Review and Assessment Service claims database. Among adult patients with preexisting IHD, new statin users and matched nonstatin users were identified on a 1:1 ratio using proportionate stratified random sampling by sex and age. They were subsequently propensity score matched further with age and comorbidities to reduce the selection bias. Overall incidence rates, cumulative rates and hazard ratios (HRs) between statin use and occurrence of NODM were estimated. The subgroup analyses were performed according to sex, age groups, and the individual agents and intensities of statins. A total of 156,360 patients (94,370 in the statin users and 61,990 in the nonstatin users) were included in the analysis. The incidence rates of NODM were 7.8% and 4.8% in the statin users and nonstatin users, respectively. The risk of NODM was higher among statin users (crude HR 2.01, 95% confidence interval [CI] 1.93–2.10; adjusted HR 1.84, 95% CI 1.63–2.09). Pravastatin had the lowest risk (adjusted HR 1.54, 95% CI 1.32–1.81) while those who were exposed to more than one statin were at the highest risk of NODM (adjusted HR 2.17, 95% CI 1.93–2.37). It has been concluded that all statins are associated with the risk of NODM in patients with IHD, and it is believed that our study would contribute to a better understanding of statin and NODM association by analyzing statin use in the real-world setting. Periodic screening and monitoring for diabetes are warranted during prolonged statin therapy in patients with IHD.

This study aimed to determine the association between statins and the prevention of dementia according to sex differences in elderly patients with ischemic heart disease (IHD). We performed a nationwide retrospective cohort study using the Korean Health Insurance Review and Assessment Service database (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015). Among the 264,036 eligible patients aged ≥65 years with IHD, statin users were compared with non-users by propensity score matching at a 1:1 ratio (71,587 in each group). The primary outcome was dementia risk by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Differential risks of dementia were assessed by sex in the subgroups of statin types, exposure duration, and patient age, implying that sex is an influential factor for the link between statin use and dementia incidence. Among seven commonly prescribed statins, rosuvastatin was associated with the greatest preventive effect on dementia incidence, with an adjusted HR of 0.82 (95% CI = 0.78-0.87). In a subgroup analysis organized by sex, the differential risk of dementia incidence was assessed in each statin group, implying that sex is an influential factor for the link between statin and dementia. This study suggests that appropriate statin use considering sex differences may have beneficial effects on the development of dementia.

Preclinical data suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors may promote metastatic progression of preexisting cancer via nuclear factor erythroid 2 related factor 2 (NRF2) activation. We aimed to investigate the association between different glucose-lowering treatments, including DPP-4 inhibitors and metformin, both with potential NRF2 modulating effects, and new-onset metastatic cancer among type 2 diabetes patients with comorbid incident cancer. This population-based cohort study included 223,530 diabetic patients newly diagnosed with primary cancer during 2009-2011 in Korea. The patients were categorized into five study cohorts in accordance with treatment modalities during the follow-up until the end of 2016: no-antidiabetic drugs (no-AD), metformin, DPP-4 inhibitors, metformin+DPP-4 inhibitors, and insulin treatment. Following propensity score (PS) matching in a 1:1 ratio against the no-AD group, 18,805 patients in metformin, 1,865 in DPP-4 inhibitors, 31,074 in metformin+DPP-4 inhibitors, and 1,895 patients in insulin groups were identified for cohort entry and analyzed against the corresponding number of no-AD patients in each PS-matched comparison pair. Metastatic risk was lower with metformin plus or minus DPP-4 inhibitors (HR 0.84, 95% CI 0.79-0.90 and 0.87, 0.80-0.95, respectively), not significantly associated with DPP-4 inhibitors (0.99, 0.77-1.29) except after thyroid cancer (3.89, 1.01-9.64), and higher with insulin therapy (1.81, 1.46-2.24) compared with no-AD use for all cancers combined. In conclusion, DPP-4 inhibitor therapy was not associated with significant risk of cancer metastasis relative to no-AD therapy, irrespective of patient age and sex, except after thyroid cancer, while metastatic risk was decreased with metformin treatment among type 2 diabetes patients with preexisting cancer. This article is protected by copyright. All rights reserved.

The most frequently added AD in diabetes patients who had switched off rosiglitazone in 2010 was pioglitazone, followed by DPP-4 inhibitors. Despite new evidence from a long-term clinical trial and the Food and Drug Administration's subsequent decision to eliminate access restrictions on rosiglitazone in 2013, domestic regulations were left intact; hence, its use remained negligible in Korea.

BackgroundAs newly available antidiabetic drugs (ADs) are used more commonly as initial hypoglycemic choice for early stage diabetes patients, there is an urgent need to investigate how these agents may differ in treatment durability relative to metformin. This study aimed to investigate the incidence and risk of treatment adjustment among newly treated type 2 diabetes mellitus (T2DM) patients receiving an oral AD as initial monotherapy.MethodsT2DM patients registered in the National Health Insurance Program who were newly prescribed an oral AD were identified. Time to treatment addition or switch to alternative antidiabetic therapy was determined using the Kaplan–Meier survival analysis. Cox proportional hazards regression was performed to estimate the hazard ratio (HR) after adjusting for potential confounding factors.ResultsThe median time to treatment adjustment was shorter for sulfonylureas (SUs), dipeptidyl peptidase-4 (DPP-4) inhibitors, alphaglucosidase (AG) inhibitors, and thiazolidinediones (TZDs) compared to that for metformin. Initiation of therapy with SUs or DPP-4 inhibitors was associated with a significantly higher risk of both treatment addition and switching than with metformin (HR 1.49 versus 1.47 for overall treatment adjustment, respectively). In contrast, among incident users of AG inhibitors or TZDs, only the hazard of switch was substantially increased compared to metformin starters (6.19, 95% confidence interval [CI] 5.77–6.64 and 7.31, 95% CI 6.35–8.42, respectively). When addition and switch events were collectively assessed, the risk of treatment adjustment was significantly elevated in all non-metformin cohorts.ConclusionOur results demonstrated that the durability of metformin as an initial monotherapy was superior to that of other ADs, including newer classes of antidiabetics, and appeared to be more effective in delaying treatment adjustment in real-world clinical practice.