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

Abstract

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.

Effects of oral antidiabetic drugs on left ventricular mass in patients with type 2 diabetes mellitus: a network meta-analysis

“…Previous research has shown LVM reduction though the administration of sulfonylureas [ 14 ], thiazolidines [ 15 ], or dipeptidyl peptidase 4(DPP4) blockers [ 16 ]. Nevertheless, some reports have also shown no significant LVM reduction upon the administration of OADs [ 17 – 19 ] and inconsistent effects.…”

Liraglutide relieves cardiac dilated function than DPP‐4 inhibitors

“…Sitagliptin and liraglutide have been shown to improve diastolic function in the short term [11][12][13][14] and diabetes mortality increases with E/e′. 15 This may be the first report of differential effects of GLP-1 analogue and DPP-4 inhibitors on cardiac diastolic function with follow-up as long as 48 months.…”

A review of dipeptidyl peptidase‐4 inhibitors. Hot topics from randomized controlled trials

“…Thus, compared to placebo, improved left ventricular performance during dobutamine stress and reduced post‐ischaemic stunning were observed both acutely and after 1 month of sitagliptin, while alogliptin was associated with better coronary flow reserve and left ventricular systolic function compared to glimepiride after 3 months, despite similar reductions in HbA1c levels . In a 24‐week study in T2DM patients, the deterioration of diastolic dysfunction (E/e’, assessed using echocardiography) was attenuated by the addition of sitagliptin compared to conventional treatment alone, although glycaemic control and blood pressure were similar in both arms of the study, and neither cardiac structure nor systolic function were affected . Moreover, pooled safety analyses of the individual inhibitors and meta‐analyses of phase 3 clinical trials had also pointed towards a potential CV risk reduction with DPP‐4 inhibitors (eg, Reference ).…”

“…In the case of the DPP-4 inhibitors, 3 of these trials have reported results; SAVOR-TIMI (saxagliptin 9 ), EXAMINE (alogliptin 10 ) and TECOS (sitagliptin 11 ), and 2 are on-going (CAROLINA 12 19 In a 24-week study in T2DM patients, the deterioration of diastolic dysfunction (E/e', assessed using echocardiography) was attenuated by the addition of sitagliptin compared to conventional treatment alone, although glycaemic control and blood pressure were similar in both arms of the study, and neither cardiac structure nor systolic function were affected. 20 Moreover, pooled safety analyses of the individual inhibitors [21][22][23][24][25] and meta-analyses of phase 3 clinical trials had also pointed towards a potential CV risk reduction with DPP-4 inhibitors (eg, Reference 14). Finally, an association between DPP-4 inhibitors and a reduction in surrogate markers of atherosclerotic CVD (carotid intima-media thickness, in some, [26][27][28] although not all 29 studies; aortic pulse wave velocity 30 ; arterial 18 F-fluorodeoxyglucose uptake 31 ) has been shown in smaller RCTs, again suggesting a possibility for a CV risk reduction.…”