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Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study.

ABSTRACT: AIM:To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database. METHODS:We identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in patients with type-2 diabetes. The main outcome was the hospitalization for HHF. Hazard ratios for HHF by type of second-line glucose-lowering medication were estimated by Cox-proportional hazard models. Sex, age, duration of MET monotherapy, Charlson Comorbidity Index and additional comorbidities, and calendar year were controlled as potential confounders. RESULTS:The observed numbers (rate per 100,000 person-years) of HHF events were 1,129 (658) for MET+SU users, 710 (455) for MET+DPP-4i users, and 110 (570) for MET+TZD users. Compared to that for MET+SU users (reference group), the adjusted hazard ratios for HHF events were 0.76 (95% confidence interval 0.69-0.84) for MET+DPP-4i users and 0.96 (95% confidence interval 0.79-1.17) for MET+TZD users. CONCLUSION:DPP-4i as an add-on therapy to MET may lower the risks of HHF compared with SU.

SUBMITTER: Lee SJ

PROVIDER: S-EPMC6370220 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study.

Lee Su Jin SJ Ha Kyoung Hwa KH Lee Jung Hyun JH Lee Hokyou H Kim Dae Jung DJ Kim Hyeon Chang HC

PloS one 20190211 2

<h4>Aim</h4>To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database.<h4>Methods</h4>We identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in pa ...[more]

PMID: 30742667

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Project description:Background Randomized controlled trials showed that newer glucose-lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT-2i, GLP-1RA, or dipeptidyl peptidase-4 inhibitors (Marketscan-Database: 2011-2017). We used multivariable Cox proportional hazards models with time-varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex-drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5-year follow-up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000-person-year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP-1RA (adjusted HR-women: 0.57, 95% CI: 0.48-0.68; aHR-men: 0.82, 0.71-0.95), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.83, 0.77-0.89; aHR-men: 0.85, 0.79-0.91) and SGLT-2i (aHR-women: 0.58, 0.46-0.74; aHR-men: 0.69, 0.57-0.83). A sex-by-drug interaction was statistically significant only for GLP-1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP-1RA (aHR-women: 0.81, 0.73-0.89; aHR-men: 0.80, 0.71-0.89), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.82, 0.78-0.87; aHR-men: 0.83, 0.78-0.87) and SGLT-2i (aHR-women: 0.68, 0.59-0.78; aHR-men: 0.67, 0.59-0.78) (all sex-drug interactions for adverse events P>0.05). Conclusions Newer glucose-lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP-1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT-2i than for GLP-1RA regardless of sex.

Project description:ObjectivesTo evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.DesignDISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019.SettingPrimary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations.ParticipantsA total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy.Primary and secondary outcome measuresThe proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change.ResultsOf the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe.ConclusionsA substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes.Trial registration numbersNCT02322762 and NCT02226822.

Project description:Background and Objective: It has been suggested to avoid cilostazol, the first-line therapy for peripheral arterial disease, in patients with congestive heart failure (HF). The objective of this study was to evaluate the risk of hospitalization for heart failure (HHF) associated with cilostazol use in the patients of diabetes mellitus. Methods: This case-crossover study retrieved records on diabetic patients > 20 years of age who were hospitalized for heart failure during the period of 2009-2011 from the Taiwan National Health Insurance Database. The "current" period was defined as 1-30 days prior to HHF whereas the 91-120 days prior to HHF served as the "reference" period. The exposure status just preceding the event is compared with exposure of the same person in one or more referent remote to the event. Adjusted odds ratios (OR) were used to estimate time-varying discordant exposure by the ratio of the number exposed to cilostazol only during the case period to the number exposed to cilostazol only during the control period. Results: A total of 47,506 diabetic patients were included in the analysis (average age: 72.7 ± 12.4, percentage of males: 48%). A total of 399 patients (0.84%) received cilostazol only in the current period, and 252 (0.53%) received cilostazol only in the reference period. After adjustment for other medications, a significant association was found between cilostazol and HHF (OR: 1.35, 95% CI: 1.14-1.59). After further adjustment for time-varying co-morbidities the ORs remained essentially the same. Sensitivity analyses using different definitions of control period (ranging from 31-60, 61-90, to 121-150 days before index date) yielded adjusted ORs of 1.43 (95% CI: 1.14-1.79), 1.31 (95% CI: 1.09-1.57) and 1.23 (95% CI: 1.06-1.44), respectively suggesting the robustness of our study findings. Conclusion: Use of cilostazol may be positively related to the risk of HHF. Further studies are warranted to explore the underlying mechanisms and to confirm the association.

Project description:ObjectivesThis study sought to describe the patterns of heart failure (HF)-exacerbating medications used among older adults hospitalized for HF and to examine determinants of HF-exacerbating medication use.BackgroundHF-exacerbating medications can potentially contribute to adverse outcomes and could represent an important target for future strategies to improve post-hospitalization outcomes.MethodsMedicare beneficiaries ≥65 years of age with an adjudicated HF hospitalization between 2003 and 2014 were derived from the geographically diverse REGARDS (Reasons for Geographic and Racial Difference in Stroke) cohort study. Major HF-exacerbating medications, defined as those listed on the 2016 American Heart Association Scientific Statement listing medications that can precipitate or induce HF, were examined. Patterns of prescribing medications at hospital admission and at discharge were examined, as well as changes that occurred between admission and discharge; and a multivariable logistic regression analysis was conducted to identify determinants of harmful prescribing practices following HF hospitalization (defined as either the continuation of an HF-exacerbating medications or an increase in the number of HF-exacerbating medications between hospital admission and discharge).ResultsAmong 558 unique individuals, 18% experienced a decrease in the number of HF-exacerbating medications between admission and discharge, 19% remained at the same number, and 12% experienced an increase. Multivariable logistic regression analysis revealed that diabetes (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.18 to 2.75]) and small hospital size (OR: 1.93; 95% CI: 1.18 to 3.16) were the strongest, independently associated determinants of harmful prescribing practices.ConclusionsHF-exacerbating medication regimens are often continued or started following an HF hospitalization. These findings highlight an ongoing need to develop strategies to improve safe prescribing practices in this vulnerable population.

Dataset Information

Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study.

Publications

Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study.

Similar Datasets

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