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Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors:A meta-analysis of cardiovascular outcome trials

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World Journal of Cardiology 2021年第10期13卷 585-592页

作者： Dimitrios Ioannis Patoulias Aristi Boulmpou Eleftherios Teperikidis Alexandra Katsimardou Fotios Siskos Michael Doumas Christodoulos E Papadopoulos Vassilios Vassilikos Second Propedeutic Department of Internal Medicine Aristotle University of ThessalonikiHippokration General HospitalThessaloniki 54642Greece Third Department of Cardiology Aristotle University of ThessalonikiHippokration General HospitalThessaloniki 54642Greece

BACKGROUND dipeptidyl peptidase-4(DPP-4)inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus(T2DM).Recently,a series of large,randomized controlled trials(RCTs)addressing cardiovascular outcomes with DPP-4 inhibitors have been *** To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac *** We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October *** extracted data concerning the following“hard”efficacy outcomes:fatal and non-fatal myocardial infarction,fatal and non-fatal stroke,hospitalization for heart failure,hospitalization for unstable angina,hospitalization for coronary revascularization and cardiovascular *** also extracted data regarding the risk for major cardiac arrhythmias,such as atrial fibrillation,atrial flutter,ventricular fibrillation and ventricular *** We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or ***-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction[risk ratio(RR)=1.02,95%CI:0.94-1.11,I2=0%],hospitalization for heart failure(RR=1.09,95%CI:0.92-1.29,I2=65%)and cardiovascular death(RR=1.02,95%CI:0.93-1.11,I2=0%).DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke(RR=0.96,95%CI:0.85-1.08,I2=0%)and coronary revascularization(RR=0.99,95%CI:0.90-1.09,I2=0%),Finally,DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina(RR=1.00,95%CI:0.85-1.18,I2=0%).As far as cardiac arrhythmias are concerned,DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation(RR=0.95,95%CI:0.78-1.17,I2=0%),whil

关键词： dipeptidyl peptidase-4 inhibitors Cardiovascular outcomes Atrial fibrillation Atrial flutter Type 2 diabetes mellitus

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Renoprotection Provided by dipeptidyl peptidase-4 inhibitors in Combination with Angiotensin Receptor Blockers in Patients with Type 2 Diabetic Nephropathy

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Chinese Medical Journal 2018年第22期131卷 2658-2665页

作者： Dan-Dan Qiu Jing Liu Jing-Song Shi Yu An Yong-Chun Ge Min-Lin Zhou Song Jiang National Clinical Research Center of Kidney Diseases Jinling HospitalNanjing University School of MedicineNanjingJiangsu 210002China Research Institute of Nephrology Jinling HospitalNanjing University School of MedicineNanjingJiangsu 210002China

Background: Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy (DN) has not been well characterized. This study aimed to assess the renoprotection of this combined treatment in DN ***: A total of 159 type 2 DN patients from 2013 to 2015 were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases, Jinling Hospital (China). Fifty-seven patients received DPP4i and ARB treatment, and 102 patients were treated with ARBs alone. All patients were followed up for at least 12 months. Statistical analyses were performed using Stata version ***: There were no significant differences at baseline for age, sex, body mass index, duration of diabetes, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) between the two groups. Antihypertensive and antidiabetic medication use was similar in each group except calcium channel antagonists (P = 0.032). No significant changes in FBG and HbA1c were observed in the two groups after treatment. The eGFR decreased slower in the DPP4i + ARB group than in the ARB group at 12 months (?12 months: -2.48 ± 13.86 vs. -6.81 ± 12.52 ml·min–1·1.73m–2,P = 0.044). In addition, proteinuria was decreased further in the DPP4i + ARB group than in the ARB group after 24 months of treatment (?24 months: -0.18 [-1.00, 0.17] vs. 0.32 [-0.35, 0.88],P = 0.031). There were 36 patients with an eGFR decrease of more than 30% over 24 months. After adjusting for FBG, HbA1c, and other risk factors, DPP4i + ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%.Conclusions: The combined treatment of DPP4i and ARBs is superior to ARBs alone, as evidenced by the greater proteinuria reduction and lower eGFR decline. In addition, the renoprotection of DPP4i combined with ARBs was independent of glycemic control.

关键词： Angiotensin Receptor Blockers Diabetic Nephropathy dipeptidyl peptidase-4 inhibitors

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Non-alcoholic fatty liver disease:Epidemiology,pathophysiology and an update on the therapeutic approaches

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Asian Pacific Journal of Tropical Biomedicine 2022年第3期12卷 99-114页

作者： Rehab F.Abdel-Rahman Department of Pharmacology Medical Research and Clinical Studies InstituteNational Research Centre12622-DokkiGizaEgypt

Non-alcoholic fatty liver disease(NAFLD)denotes a spectrum of fatty liver disease in individuals without significant alcohol *** is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 *** is further histologically categorized into the non-alcoholic fatty liver(NAFL;steatosis without hepatocellular injury)and non-alcoholic steatohepatitis(NASH)which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury(ballooning),either with or without *** is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in ***,NASH is a more progressive stage of NAFLD,due to the increased risks of evolving more serious diseases such as cirrhosis,hepatocellular *** concept,however,has been lately challenged by a hypothesis of multiple parallel hits of NAFLD,in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum,not only from a set of histological patterns but also from a pathophysiological *** current review highlights the epidemiology and pathophysiology of NAFLD,and its progression towards steatohepatitis,with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development,and progression of NAFLD.

关键词： Non-alcoholic fatty liver disease Steatosis Insulin sensitizers Glucagon-like peptide-1 analogues dipeptidyl peptidase-4 inhibitors Farnesoid X receptor agonists

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DPP-4 inhibitors and GLP-1RAs:cardiovascular safety and benefits

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Military Medical Research 2023年第2期10卷 227-241页

作者： Michael Razavi Ying-Ying Wei Xiao-Quan Rao Ji-Xin Zhong Tulane University School of Medicine New OrleansLA 70112USA Department of Rheumatology and Immunology Tongji HospitalTongji Medical College of Huazhong University of Science and Technology1095 Jiefang AveWuhan 430032China Department of Cardiovascular Medicine Tongji HospitalTongji Medical College of Huazhong University of Science and Technology1095 Jiefang AveWuhan 430032China Institute of Allergy and Clinical Immunology Tongji HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhan 430032China

Glucagon-like peptide-1 receptor agonists(GLP-1RAs)and dipeptidyl peptidase-4 inhibitors are commonly used treatments for patients with type 2 diabetes mellitus(T2DM).Both anti-diabetic treatments function by playing key modulatory roles in the incretin *** these drugs have been deemed effective in treating T2DM,the Food and Drug Administration(FDA)and some members of the scientific community have questioned the safety of these therapeutics relative to important cardiovascular *** a result,since 2008,the FDA has required all new drugs for glycemic control in T2DM patients to demonstrate cardiovascular *** present review article strives to assess the safety and benefits of incretin-based therapy,a new class of antidiabetic drug,on the health of patient cardiovascular *** the process,this review will also provide a physiological overview of the incretin system and how key components function in T2DM.

关键词： Glucagon-like peptide-1 receptor agonists dipeptidyl peptidase-4 inhibitors Type 2 diabetes mellitus Cardiovascular outcome

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Recent advances in new-onset diabetes mellitus after kidney transplantation

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World Journal of Diabetes 2021年第5期12卷 541-555页

作者： Tess Montada-Atin G V Ramesh Prasad Kidney Transplant Program St.Michael's HospitalToronto M5C 2T2OntarioCanada Department of Medicine University of TorontoToronto M5C 2T2Canada

A common challenge in managing kidney transplant recipients(KTR)is posttransplant diabetes mellitus(PTDM)or diabetes mellitus(DM)newly diagnosed after transplantation,in addition to known pre-existing *** is an important risk factor for post-transplant cardiovascular(CV)disease,which adversely affects patient survival and quality of *** disease in KTR may manifest as ischemic heart disease,heart failure,and/or left ventricular *** therapies for PTDM include most agents currently used to treat type 2 *** recently,the use of sodium glucose co-transporter 2 inhibitors(SGLT2i),glucagon-like peptide-1 receptor agonists(GLP-1 RA),and dipeptidyl peptidase 4 inhibitors(DPP4i)has cautiously extended to KTR with PTDM,even though KTR are typically excluded from large general population clinical *** evidence from observational studies seems to indicate that SGLT2i,GLP-1 RA,and DPP4i may be safe and effective for glycemic control in KTR,but their benefit in reducing CV events in this otherwise high-risk population remains *** newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status,pre-existing burden of peripheral vascular disease,urinary tract infections due to immunosuppression and a surgically altered urinary tract,erythrocytosis from calcineurin inhibitors,and reduced kidney function from acute or chronic rejection.

关键词： Cardiovascular disease Glucagon-like peptide-1 receptor agonists Kidney transplantation Oral antihyperglycemic drugs Post-transplant diabetes mellitus Sodium glucose co-transporter 2 inhibitors dipeptidyl peptidase-4 inhibitors

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dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases:Current evidence

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World Journal of Diabetes 2021年第9期12卷 1426-1441页

作者： Ayan Roy Jayaprakash Sahoo Niya Narayanan Chandhana Merugu Sadishkumar Kamalanathan Dukhabandhu Naik Department of Endocrinology and Metabolism All India Institute of Medical SciencesJodhpur 342005India Department of Endocrinology Jawaharlal Institute of Postgraduate Medical Education and ResearchPuducherry 605006India

dipeptidyl peptidase-4 inhibitors(DPP-4i)have an important place in the management of type 2 *** DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological ***-4 regulates several immune functions,including T-cell activation,macrophage function,and secretion of *** have reported an increase in autoimmune diseases like bullous pemphigoid,inflammatory bowel disease,and arthritis with DPP-4i *** relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more *** a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious ***,a heightened awareness from the clinicians is required to identify and treat any such *** this review,we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.

关键词： Autoimmune disease Bullous pemphigoid Diabetes dipeptidyl peptidase-4 inhibitors Gliptins Inflammation

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Clinical effects of antidiabetic drugs on psoriasis:The perspective of evidence-based medicine

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World Journal of Diabetes 2021年第8期12卷 1141-1145页

作者： Mei-Xian Zhang Bo-Yuan Zheng Hai-Xiao Chen Ching-Wen Chien Evidence-based Medicine Center Taizhou Hospital of Zhejiang ProvinceWenzhou Medical UniversityLinhai 317000Zhejiang ProvinceChina Public Laboratory Taizhou Hospital of Zhejiang ProvinceWenzhou Medical UniversityLinhai 317000Zhejiang ProvinceChina Institute for Hospital Management Tsing Hua UniversityShenzhen CampusShenzhen 518055Guangdong ProvinceChina Department of Orthopedics Taizhou Hospital of Zhejiang ProvinceWenzhou Medical UniversityLinhai 317000Zhejiang ProvinceChina

Psoriasis and diabetes shared common underlying pathophysiological *** data suggested that antidiabetic medications may improve the psoriasis severity in patients with diabetes *** hypoglycemic agents including thiazolidinediones,glucagon-like peptide-1 receptor agonists,dipeptidyl peptidase-4 inhibitors,and biguanides have been reported to make a remarkable reduction in the Psoriasis Area and Severity Index score from *** antipsoriatic effect could be mediated not only by the glucoselowering action of these agents but also via inhibition of keratinocyte over proliferation,increase expression of differentiation markers,suppression the immune inflammatory pathway,and blocking the calcium channels and mitogen-activated protein kinase signaling *** the other hand,there was no significant increase in adverse reactions associated with the treatment of pioglitazone or ***,previous studies often had the relatively short duration of the trials,and did not have enough power to assess recurrence of *** bias in the study and missing data could undermine the reliability of the ***,the appropriately randomized controlled studies with large sample sizes and long-term durations in various psoriasis patients are warranted for further support.

关键词： Psoriasis Hypoglycemic agents Thiazolidinediones Glucagon-like peptide-1 receptor agonists dipeptidyl peptidase-4 inhibitors Biguanides Antipsoriatic effect Evidence-based medicine

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Glucose lowering does not necessarily reduce cardiovascular risk in type 2 diabetes

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World Journal of Cardiology 2022年第4期14卷 266-270页

作者： Angeliki Bourazana Grigorios Giamouzis John Skoularigis Filippos Triposkiadis Andrew Xanthopoulos Department of Cardiology University Hospital of LarissaLarissa 41110Greece

Diabetes mellitus(DM)is a health condition characterized by glucose dysregulation and affects millions of people *** presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum,commencing from asymptomatic,subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality ***,the spectrum of systolic dysfunction in diabetic-induced heart failure is *** leads also to cardiac electrical remodeling reacting on various *** peptidase-4(DPP-4)inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 *** DPP-4 inhibitors’efficacy regarding glycemic control,their effect on cardiovascular outcomes(myocardial infarction,stroke,hospitalization for heart failure,hospitalization for unstable angina,hospitalization for coronary revascularization,and cardiovascular death)in diabetic patients has been *** potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.

关键词： dipeptidyl peptidase-4 inhibitors Diabetes mellitus Outcomes Metaanalysis Heart failure Atrial flutter

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Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

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World Journal of Cardiology 2024年第8期16卷 448-457页

作者： Petra Grubić Rotkvić Luka Rotkvić Ana Đuzel Čokljat Maja Cigrovski Berković Department of Cardiology University Hospital Centre ZagrebZagreb 10000Croatia Department of Cardiology Magdalena Clinic for Cardiovascular DiseaseKrapinske Toplice 49217Croatia Department of Internal Medicine General Hospital DubrovnikDubrovnik 20000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of *** previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic *** groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic *** To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body *** The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood *** evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was *** There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of *** independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy *** SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic *** control contributes to the i

关键词： Sodium-dependent glucose transporter 2 inhibitors dipeptidyl peptidase-4 inhibitors Type 2 diabetes mellitus Heart failure Diabetic cardiomyopathy Cardiovascular disease

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Incretin-based therapies in prediabetes: Current evidence and future perspectives

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World Journal of Diabetes 2014年第6期5卷 817-834页

作者： Georgios S Papaetis Internal Medicine and Diabetes Clinic

The prevalence of type 2 diabetes(T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance(NGT) and the clinical entity of T2 D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2 D. The huge burden resulting from the complications of T2 D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists, on β-cell function in patients with T2 D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2 D.

关键词： Type 2 diabetes Prediabetes Impaired fasting glucose Impaired glucose tolerance Glucagon-like peptide-1 dipeptidyl peptidase-4 inhibitors Glucagon-like peptide-1 receptor agonists

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