Dipeptidyl peptidase-4 inhibitors and their potential role in the management of atherosclerosis—A review

Singh, Tejas P.; Vangaveti, Venkat; Malabu, Usman H.

doi:10.1016/j.dsx.2015.04.005

Cited by 18 publications

(20 citation statements)

References 55 publications

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“…The possible impact of DPP-4i on post-AMI survival may derive from their cardioprotective effects and their beneficial effect on cardiovascular risk factors such as atherosclerosis and hypertension [4–8, 31–36]. In Japanese patients with diabetes and multiple CV risk factors, DPP4i was shown to decrease blood pressure associated with an improvement in albuminuria in addition to glycemic control [17].…”

Section: Discussionmentioning

confidence: 99%

The impact of DPP-4 inhibitors on long-term survival among diabetic patients after first acute myocardial infarction

Wang

Lin

Tang

et al. 2017

Cardiovasc Diabetol

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BackgroundPrevious studies regarding the cardioprotective effects of dipeptidyl peptidase 4 (DPP-4) inhibitors have not provided sufficient evidence of a relationship between DPP-4 inhibition and actual cardiovascular outcomes. This study aimed to evaluate the impact of DPP-4 inhibitors on the survival of diabetic patients after first acute myocardial infarction (AMI).MethodsThis was a nationwide, propensity score-matched, case–control study of 186,112 first AMI patients, 72,924 of whom had diabetes. A propensity score, one-to-one matching technique was used to match 2672 controls to 2672 patients in the DPP-4 inhibitor group for analysis. Controls were matched based on gender, age, and a history of hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accident, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention.ResultsDPP-4 inhibitors improve the overall 3-year survival rate (log rank P < 0.0001), whether male or female. Cox proportional hazard regression showed DPP-4 inhibitor is beneficial in diabetes patients after AMI (HR = 0.86; 95% CI 0.78–0.95), especially in those patients with hypertension (HR = 0.87; 95% CI 0.78–0.97; P = 0.0103) and cerebrovascular disease (HR = 0.83; 95% CI 0.72–0.97; P = 0.018), but without dyslipidemia (HR = 0.78; 95% CI 0.67–0.92; P = 0.0029), without peripheral vascular disease (HR = 0.86; 95% CI 0.78–0.96; P = 0.0047), without heart failure (HR = 0.84; 95% CI 0.73–0.96; P = 0.0106), without end stage renal disease (HR = 0.86; 95% CI 0.77–0.95; P = 0.0035), and without chronic obstructive pulmonary disease (HR = 0.87; 95% CI 0.78–0.97; P = 0.0096).ConclusionsDPP-4 inhibitor therapy improved long-term survival in diabetic patients after first AMI, regardless of gender.

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Section: Discussionmentioning

confidence: 99%

The impact of DPP-4 inhibitors on long-term survival among diabetic patients after first acute myocardial infarction

Wang

Lin

Tang

et al. 2017

Cardiovasc Diabetol

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“…In a recent review, attempting to compare different DPP-4 inhibitor effects on pro- and antiatherogenic factors, only few studies on saxagliptin have been performed [15]. …”

Section: Discussionmentioning

confidence: 99%

A Double-Blinded Randomized Study Investigating a Possible Anti-Inflammatory Effect of Saxagliptin versus Placebo as Add-On Therapy in Patients with Both Type 2 Diabetes And Stable Coronary Artery Disease

Njerve

Åkra

Weiss

et al. 2017

Mediators of Inflammation

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Background Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Methods Patients (n = 12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at −150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). Results HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo (p = 0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group (p = 0.043, both), significantly different from that in the placebo (p = 0.009 and p = 0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. Conclusion In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies.

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“…Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel class of glucose-lowering drugs [6]. Various studies suggest DPP4 inhibitors may also possess cardioprotective effect [7–12], including atherosclerosis [13–15]. In the current review, we will summarize the recent advances in direct and indirect regulatory role of DPP4 in cardiovascular disease, especially in atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

The regulatory role of DPP4 in atherosclerotic disease

Duan

Rao

Xia

et al. 2017

Cardiovasc Diabetol

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The increasing prevalence of atherosclerosis has become a worldwide health concern. Although significant progress has been made in the understanding of atherosclerosis pathogenesis, the underlying mechanisms are not fully understood. Recent studies suggest dipeptidyl peptidase-4 (DPP4), a regulator of inflammation and metabolism, may be involved in the development of atherosclerotic diseases. There has been increasing clinical and pre-clinical evidence showing DPP4-incretin axis is involved in cardiovascular disease. Although the cardiovascular outcome of DPP4 inhibition or incretin analogues has been or being evaluated by several large scale clinical trials, the exact role of DPP4 in atherosclerotic diseases is not completely understood. In the current review, we will summarize the recent advances in direct and indirect regulatory role of DPP4 in atherosclerosis.

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Dipeptidyl peptidase-4 inhibitors and their potential role in the management of atherosclerosis—A review

Cited by 18 publications

References 55 publications

The impact of DPP-4 inhibitors on long-term survival among diabetic patients after first acute myocardial infarction

The impact of DPP-4 inhibitors on long-term survival among diabetic patients after first acute myocardial infarction

A Double-Blinded Randomized Study Investigating a Possible Anti-Inflammatory Effect of Saxagliptin versus Placebo as Add-On Therapy in Patients with Both Type 2 Diabetes And Stable Coronary Artery Disease

The regulatory role of DPP4 in atherosclerotic disease

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