Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials

Rehman, Michaela B.; Tudrej, B.V.; Soustre, J.; Buisson, Marielle; Archambault, P.; Pouchain, Denis; Vaillant-Roussel, Hélène; Gueyffier, François; Faillie, Jean‐Luc; Pérault‐Pochat, Marie‐Christine; Cornu, Catherine; Boussageon, Rémy

doi:10.1016/j.diabet.2016.09.005

Cited by 94 publications

(66 citation statements)

References 26 publications

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“…In fact, treatment with a GLP-1 agonist, one of the incretin-related agents, was shown to improve diastolic function beyond and independent of glycemic control [43]. Because there remains clinical caution regarding DPP-4 inhibitor-induced heart failure [44, 45], further experimental and clinical research is required to elucidate the precise mechanisms by which DPP-4 inhibitors affect diastolic function and heart failure in patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study

Yamada

Tanaka

Kusunose

et al. 2017

Cardiovasc Diabetol

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BackgroundDiabetes is associated closely with an increased risk of cardiovascular events, including diastolic dysfunction and heart failure that leads to a shortening of life expectancy. It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function. However, the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern. We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub-analysis of the PROLOGUE study.MethodsPatients in the PROLOGUE study were assigned randomly to either add-on sitagliptin treatment or conventional antidiabetic treatment. Of the 463 patients in the overall study, 115 patients (55 in the sitagliptin group and 60 in the conventional group) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included in this study. The primary endpoint of this post hoc sub-analysis was a comparison of the changes in the ratio of E to e′ (E/e′) between the two groups from baseline to 24 months.ResultsThe baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group (−0.18 ± 0.55 vs. 1.91 ± 0.53, p = 0.008), irrespective of a higher E/e′ value at baseline in the sitagliptin group. In analysis of covariance, sitagliptin treatment was significantly associated with change in E/e′ over 24 months (β = −9.959, p = 0.001), independent of other clinical variables at baseline such as blood pressure, HbA1c, and medications for diabetes. Changes in other clinical variables including blood pressure and glycemic parameters, and echocardiographic parameters, such as cardiac structure and systolic function, were comparable between the two groups. There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period.ConclusionsAdding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction (E/e′) independent of other clinical variables such as blood pressure and glycemic control. Trial registration UMIN000004490 (University Hospital Medical Information Network Clinical Trials). https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356; registered November 1, 2010Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0546-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study

Yamada

Tanaka

Kusunose

et al. 2017

Cardiovasc Diabetol

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“…The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, which act in a blood glucose-dependent manner, carries a low risk of hypoglycemia [11]. In Japan, DPP-4 inhibitors, including teneligliptin (TNL), are the most commonly prescribed antidiabetic drugs [12], and are suitable for both elderly and dialysis patients [13].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

Kadowaki

Kondo

Sasaki

et al. 2017

Expert Opinion on Pharmacotherapy

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“…Our data are in line with the results from a meta‐analysis of randomized studies for vildagliptin, a meta‐analysis for DPP‐4 inhibitors based on observational data only or of both, observational and RCTs and various noninterventional studies which reported no increased risk of acute pancreatitis compared to DPP‐4 inhibitor nonusers. In contrast, a recent noninterventional study and a meta‐analysis of three large randomized DPP‐4 inhibitor outcome trials (none of which included vildagliptin) reported an increased risk of pancreatitis.…”

Section: Discussionmentioning

confidence: 84%

“…The well‐established benefit‐risk profile of DPP‐4 inhibitors however, has been challenged because of safety concerns regarding adverse pancreatic events (acute pancreatitis, pancreatic cancer) which was initially raised by postmarketing surveillance reports from the Food and Drug Administration Adverse Event Reporting System . While some noninterventional studies or meta‐analyses of randomized controlled trials (RCTs) reported an increased risk of pancreatic events, other studies did not find an increased risk …”

Section: Introductionmentioning

confidence: 99%

Pancreatic safety of vildagliptin in patients with type 2 diabetes mellitus: A European, noninterventional, postauthorization safety study

Williams

Kothny

Serban

et al. 2019

Endocrino Diabet & Metabol

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This cohort study assessed the pancreatic safety of vildagliptin versus other noninsulin antidiabetic drugs (NIADs) based on data from five European electronic health care databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated separately for acute pancreatitis and pancreatic cancer for vildagliptin (± other NIADs) compared with other NIADs using negative binomial regression. Approximately 2.8% of the enrolled patients (n = 738 054) used vildagliptin during the study, with an average follow‐up time of 1.4 years. For acute pancreatitis, adjusted IRRs ranged between 0.89 andt 2.58 with all corresponding 95% CIs crossing 1. For pancreatic cancer adjusted IRRs ranged from 0.56 to 3.64, with the lower limit of 95% CIs >1 in some analyses. Post hoc sensitivity analyses taking latency time into account markedly lowered the risk estimates with corresponding 95% CIs crossing 1. Overall, the results do not suggest an increased pancreatitis risk with vildagliptin, while the observation for pancreatic cancer have to be interpreted carefully as this study was not designed to assess pancreatic cancer and rather be explained by certain underlying limitations including latency ‐time, chance findings and/or bias and confounding.

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Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials

Cited by 94 publications

References 26 publications

Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study

Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

Pancreatic safety of vildagliptin in patients with type 2 diabetes mellitus: A European, noninterventional, postauthorization safety study

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