Dipeptidyl peptidase-4 inhibitor cardiovascular safety in patients with type 2 diabetes, with cardiovascular and renal disease: a retrospective cohort study.
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SUBMITTER: Baksh S
PROVIDER: S-EPMC8371013 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes.MethodsUsing a new-user retrospective cohort derived from IBM MarketScan Commercial Claims and Encounters (2010-2015), we identified patients aged 35-65 with type 2 diabetes, without cardiovascular or renal disease, initiating DPP-4i, sulfonylureas, or metformin. Primary composite outcome of time to first MACE was defined as the first of any of the following: myocardial infarction, cardiac arrest, coronary artery bypass graft, coronary angioplasty, heart failure, and stroke. Secondary outcomes were time to first heart failure, acute myocardial infarction, and stroke. We compared outcomes for DPP-4i versus sulfonylurea and DPP-4i versus metformin using propensity score weighted Cox proportional hazards, adjusting for demographics, baseline comorbidities, concomitant medications, and cumulative exposure.ResultsOf 445,701 individuals, 236,431 (53.0%) were male, median age was 51 (interquartile range: [44, 57]), 30,267 (6.79%) initiated DPP-4i, 52,138 (11.70%) initiated sulfonylureas, and 367,908 (82.55%) initiated metformin. After adjustment, DPP-4i was associated with lower risk of MACE than sulfonylurea (adjusted hazard ratio (aHR) = 0.87; 95% confidence interval (CI): 0.78-0.98), and similar risk to metformin (aHR = 1.07; 95% CI: 0.97-1.18). Risk for acute myocardial infarction (aHR = 0.70; 95% CI: 0.51-0.96), stroke (aHR = 0.57; 95% CI: 0.41-0.79), and heart failure (aHR = 0.57; 95% CI: 0.41-0.79) with DPP-4i was lower compared to sulfonylureas.ConclusionOur findings show that for this cohort of low-risk patients newly treated for type 2 diabetes, DPP-4i exhibited 13% lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin, suggesting DPP-4i is a low cardiovascular risk option for low-risk patients initiating antihyperglycemic treatment.
| S-EPMC7561135 | biostudies-literature
Project description:Incretin based therapies have been introduced into the treatment options of type 2 diabetes a few years ago. Among them, the orally active DPP-4 inhibitors have established themselves as insulinotropic agents. Their advantage is the glucose-dependent insulinotropic action without an intrinsic risk for causing hypoglycemia. Additionally DPP-4 inhibitors have a glucose dependent glucagonostatic action contributing to improved glucose control. They are weight neutral and show a good safety and tolerability profile with comparable efficacy to sulfonylureas. Linagliptin is a novel DPP-4 inhibitor with a distinct pharmacological profile. In contrast to the other approved DPP-4 inhibitors it is eliminated by a hepatic/biliary route rather than a renal route. Therefore no dose adjustment is recommended in patients with type 2 diabetes and renal impairment. In clinical studies, it has been shown to be non-inferior to sulfonylurea treatment regarding glycemic parameters, but to possess favourable safety advantages regarding hypoglycemia frequency, body weight development and effects on cardioavascular parameters. This article gives an overview on the pharmacology of linagliptin as well as on the clinical data available.
| S-EPMC3411498 | biostudies-literature
Project description:IntroductionThe use of antihyperglycemic agents (AHA), especially insulin and sulfonylureas (SU), is a risk factor for hypoglycemia. Despite the significant clinical and economic burdens associated with hypoglycemia and the decreasing use of SU in favor of other oral AHA, relatively little is known about hypoglycemia trends specific to the use of non-insulin AHA. We sought to estimate annual hypoglycemia event rates and costs among patients with type 2 diabetes mellitus (T2DM) who started either SU or dipeptidyl peptidase-4 inhibitors (DPP-4i) and to predict rates and costs in the absence of DPP-4i.MethodsTruven's MarketScan Commercial Claims database was used to estimate hypoglycemia event rates and costs from 2007 to 2013. Hypoglycemia, defined using diagnosis codes, was assessed during the 12 months following SU (n = 245,201) or DPP-4i (n = 176,786) initiation by adults with T2DM. Coefficients from a Poisson regression model used to estimate the impact of patient characteristics on hypoglycemia rates for patients who started SU were used to predict rates for patients who started DPP-4i had they started SU instead.ResultsHypoglycemia events per 100 patient-years (costs per event) ranged from 5.4 ($565) in 2007 to 10.4 ($1154) in 2013 for patients starting SU; rates (costs) for patients starting DPP-4i ranged from 3.2 ($308) in 2007 to 6.4 ($482) in 2013. Predicted hypoglycemia rates would have been 5.3-9.9 per 100 person-years for patients who started DPP-4i had they started SU instead. Starting DPP-4i, rather than SU, would have resulted in national savings of $750.3 million in healthcare costs due to avoided hypoglycemia events during this period.ConclusionsHypoglycemia rates and costs were consistently higher for patients who started SU rather than DPP-4i. The overall burden of hypoglycemia could be lowered substantially in the USA if, when feasible, patients with T2DM initiate DPP-4i instead of SU.FundingMerck & Co., Inc., Kenilworth, NJ USA.
| S-EPMC6250633 | biostudies-literature
Project description:BackgroundTo determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort.MethodsFrom a nationwide cohort in Korea (2008-2013), 23,674 patients with type 2 diabetes treated with DPP4i plus metformin or SU plus metformin were selected and matched by propensity score. Composite cardiocerebrovascular events including incident ischemic heart disease (IHD), ischemic stroke (IS), hospitalization for heart failure (HHF), and cardiocerebrovascular death, as well as renal events including incident end-stage renal disease or initiation of renal-replacement therapy were assessed by Cox proportional-hazards models.ResultsDuring a median follow-up of 19.6 months (interquartile range 7.2-36.4), 762 composite cardiocerebrovascular events and 17 end-stage renal events occurred. There was no significant difference in the risk of IHD (hazard ratio [HR], 1.00; 95% CI 0.81-1.23), IS (HR, 0.95; 95% CI 0.74-1.23), or cardiocerebrovascular death (HR, 0.74; 95% CI 0.46-1.18) in the DPP4i group compared to that in the SU group. Likewise, DPP4i therapy was not associated with the risk of end-stage renal outcomes (HR, 1.23; 95% CI 0.41-3.62). However, the risk of HHF was significantly higher in the DPP4i group than in the SU group (HR, 1.47; 95% CI 1.07-2.04).ConclusionsThis real-world database analysis showed that DPP4i therapy did not increase the overall risk of major cardiovascular and renal outcomes compared to SU therapy. However, the DPP4i-associated risk of HHF remained significant.
| S-EPMC6410523 | biostudies-literature
Project description:Two recent randomized controlled trials of type 2 diabetes mellitus (T2DM) patients with history of, or at high risk of, cardiovascular disease (CVD) showed no risk of ischemic cardiovascular events associated with dipeptidyl peptidase-4 inhibitors (DPP4i), but an increased risk of heart failure (HF) with saxagliptin. We evaluated the risk of CVD including myocardial infarction (MI), stroke, coronary revascularization, and HF associated with DPP4i in T2DM patients with and without baseline CVD as used in the community.Using US commercial insurance claims data (2005-2012), we conducted a cohort study that included initiators of DPP4i and non-DPP4i treatments. Composite CVD endpoints including MI, stroke, coronary revascularization, and HF were defined with a hospital discharge diagnosis or procedure code. Cox proportional hazards models compared the risk of composite and individual CVD endpoints in propensity score (PS)-matched initiators of DPP4 versus non-DPP4i.We included 79,538 (18 % with baseline CVD) persons in PS-matched pairs of DPP4i and non-DPP4i initiators. The incidence rate per 1,000 person-years for composite CVD was 30.30 (95 % CI 28.24-32.51) in DPP4i and 34.76 (95 % CI 32.34-37.36) in non-DPP4i. The PS-matched hazard ratio (HR) for composite CVD was 0.87 (95 % CI 0.79-0.96) in DPP4i versus non-DPP4i. The PS-matched HR for HF was 0.81 (95 % CI 0.70-0.94) in DPP4i versus non-DPP4i. Among patients with baseline CVD, there was no increased risk of CVD or HF associated with DPP4i use.Among T2DM patients, initiating DPP4i was not associated with a greater risk of CVD or HF compared to non-DPP4i initiators.
| S-EPMC4241160 | biostudies-literature
Project description:BackgroundIn recent years, dipeptidyl peptidase (DPP)-4 inhibitors have been added to the diabetes treatment algorithm. Few published studies have shown that the use of DPP-4 inhibitors is associated with joint pain. To our knowledge, no population-based studies in the United States have studied this association.ObjectiveTo evaluate the association between a new prescription of DPP-4 inhibitors and joint pain within 1 year among older veterans with diabetes.MethodsThis was a retrospective cohort study of older veterans (aged ≥66 years) who were dually enrolled in Medicare and the Veterans Health Administration (VHA; N = 134,488). Data were derived from linked Medicare claims and VHA electronic health records from 2008 to 2010. Diabetes during the baseline and joint pain during the follow-up period were identified with International Classification of Diseases, Ninth Revision codes. Filled prescriptions for DPP-4 inhibitors during the baseline period were identified from Medicare Part D and VHA pharmacy records. The adjusted associations between DPP-4 inhibitors and joint pain were examined with logistic regressions.ResultsApproximately 8.4% of the 134,488 study patients received at least 1 prescription for DPP-4 inhibitors and 11.7% were diagnosed with joint pain during the follow-up period. An unadjusted analysis showed significant differences in joint pain by DPP-4 inhibitor status (12.9% among users vs 11.6% among nonusers; P <.0001). In a fully adjusted model, having a DPP-4 inhibitor prescription had higher odds of joint pain (adjusted odds ratio, 1.17; 95% confidence interval, 1.10-1.24) compared with no prescription for a DPP-4 inhibitor.ConclusionIn a cohort of older veterans who did not have documented joint pain at baseline, a prescription for DPP-4 inhibitors was significantly associated with a newly documented joint pain.
| S-EPMC6979048 | biostudies-literature
Project description:BACKGROUND/OBJECTIVES:Data on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin. METHODS:We conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score. RESULTS:During follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively. CONCLUSIONS:Compared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.
| S-EPMC4439115 | biostudies-literature
Project description:IntroductionClinical trials conducted in patients with type 2 diabetes (T2DM) treated with glucose-lowering drugs and examining cardiovascular-related outcomes have yielded mixed results. In this work, we aimed to assess the relative treatment effects of empagliflozin versus sitagliptin and saxagliptin (dipeptidyl peptidase-4 (DPP-4) inhibitors) on cardiovascular-related outcomes in patients with T2DM.MethodsWe conducted a systematic literature review to identify clinical trials assessing cardiovascular-related outcomes for sitagliptin-, saxagliptin-, and empagliflozin-treated patients with T2DM. A network meta-analysis of indirect treatment comparisons was conducted in a Bayesian framework. Hazard ratios (HR) and 95% credible intervals (CrI) were computed for six cardiovascular-related outcomes to estimate the relative efficacies of these agents.ResultsEmpagliflozin showed a statistically significant superiority over saxagliptin (HR 0.60; 95% CrI 0.46-0.80) and sitagliptin (HR 0.60; 95% CrI 0.46-0.79) to reduce the risk for cardiovascular-related mortality. For all-cause mortality, empagliflozin showed a statistically significant risk reduction compared to saxagliptin (HR 0.61; 95% CrI 0.49-0.76) and sitagliptin (HR 0.67; 95% CrI 0.54-0.83). A similar pattern was observed in the risk reduction for hospitalization due to heart failure, where empagliflozin was found to be statistically significantly superior to saxagliptin (HR 0.51; 95% CrI 0.37-0.70) and sitagliptin (HR 0.65; 95% CrI 0.47-0.90). Empagliflozin was not statistically significantly different to sitagliptin and saxagliptin with regard to the risk of a composite endpoint composed of death, stroke or myocardial infarction.ConclusionIn this indirect comparison to the DPP-4 inhibitors saxagliptin and sitagliptin, empagliflozin significantly lowered the risk of cardiovascular-related mortality, all-cause mortality and hospitalizations due to heart failure.FundingBoehringer Ingelheim GmbH.
| S-EPMC6064600 | biostudies-literature
Project description:Whether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear. This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes.Over a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan's National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled. Patients were further divided into two groups: (1) DPP4i users: those taking DPP4i and (2) non-DPP4i users: those prescribed other hypoglycemic agents (HAs) as second-line drug. Study end point was defined by diagnosis of AF, addition of any third-line HA, or the end of the study period (December 31, 2013), whichever came first.A total of 16,017 DPP4i users and 74,863 non-DPP4i users were eligible for the study. For the DPP4i group, most patients were prescribed sitagliptin (n = 12,180; 76%). Among the non-DPP4i group, most patients took sulfonylurea (n = 60,606; 81%) as their second-line medication. DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i users after propensity-score weighting (hazard ratio 0.65; P < 0.0001). Subgroup analysis showed that DPP4i user were associated with a lower risk of new-onset AF compared with non-DPP4i users in most subgroups. Multivariate analysis indicated that use of DPP4i was associated with lower risk of new-onset AF and age > 65 years, presence of hypertension, and ischemic heart disease were independent risk factors for new-onset AF.Among patients with diabetes prescribed with metformin, the patients with DPP4i as second HA were associated with a lower risk of AF compared with the patients with other drugs as second HAs in real-world practice.
| S-EPMC5735601 | biostudies-literature
Project description:BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group).MethodsThis was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction.ResultsTwenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index.ConclusionThere was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.
| S-EPMC8476296 | biostudies-literature