Efficacy and Safety of Vildagliptin in New-Onset Diabetes After Kidney Transplantation—A Randomized, Double-Blind, Placebo-Controlled Trial

Haidinger, Michael; Werzowa, Johannes; Hecking, Manfred; Antlanger, Marlies; Stemer, Gunar; Pleiner, Johannes; Kopecky, Chantal; Kovarík, J; Döller, Dominik; Pacini, Giovanni; Säemann, Marcus D.

doi:10.1111/ajt.12518

Cited by 101 publications

(58 citation statements)

References 57 publications

(86 reference statements)

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“…The number of oral drugs available for treatment of hyperglycemia in renal transplant recipients is limited because many recipients often have reduced renal function and because of the potential interactions with immunosuppressive drugs and adverse effects such as hypoglycemic events, which may increase the cardiovascular risk. Efficacy and safety of the dipeptidyl peptidase-4 inhibitors sitagliptin (36,37) and vildagliptin (38,39) have previously been documented in PTDM patients. The insulinotropic and glucagonostatic effects of GLP-1 described in the current study imply that GLP-1 analogues also could be an alternative in the treatment of PTDM.…”

Section: Discussionmentioning

confidence: 99%

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

et al. 2016

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OBJECTIVEDevelopment of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively. RESEARCH DESIGN AND METHODSRenal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp. RESULTSFasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 6 12 vs. 65 6 12%, P < 0.001), while first-and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first-and second-phase insulin secretion in both groups. CONCLUSIONSPTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.In renal transplant recipients, cardiovascular disease persists as the leading cause of premature death (1). Development of posttransplantation diabetes (PTDM) is associated with further increased cardiovascular risk and mortality (2-4). PTDM is primarily believed to be a variant of type 2 diabetes possibly induced by immunosuppressive therapy (5) and/or viral infections (e.g., cytomegalovirus and hepatitis C) that reduce both insulin secretion and insulin sensitivity (6). Importantly, the risk of PTDM can be significantly reduced by proper dosing of the immunosuppressive

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Section: Discussionmentioning

confidence: 99%

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

et al. 2016

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“…В ис-следование было включено 33 реципиента, перенесших пересадку более 6 месяцев назад, со стабильно функ-ционирующим трансплантатом. По результатам четы-рехмесячного наблюдения, различий в СКФ и частоте нежелательных явлений между группами вилдаглиптина и плацебо не выявлено [92].…”

Section: ингибиторы дпп-4unclassified

Incretin-based therapy: renal effects

Korbut¹,

Климонтов²

2016

Diabetes mellitus

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© Сахарный диабет, 2016ерапия, основанная на модификации эффекта инкретиновых гормонов, -сравнительно новое направление в лечении сахарного диабета 2 типа (СД2). Аналоги глюкагоноподобного пептида 1 типа (ГПП-1) и ингибиторы дипептидилпептидазы 4 типа (ДПП-4) обладают широким спектром фармакологиче-ского действия, включающего гликемические и неглике-мические эффекты. В последние годы большой интерес вызывает способность препаратов данных классов вли-ять на развитие осложнений СД. В настоящем обзоре обобщены результаты экспериментальных и клиниче-ских исследований, посвященных изучению эффектов агонистов ГПП-1 и ингибиторов ДПП-4 на структурно-функциональные изменения в почках при СД. Поиск источников проведен в базах данных Medline/PubMed, Scopus, Web of Science, eLibrary, ClinicalTrials.gov, а также в электронных базах материалов конгрессов Американ-ской диабетической ассоциации (ADA) и Европейской ассоциации по изучению сахарного диабета (EASD). Представлены результаты оригинальных исследований и мета-анализов, опубликованных на русском и англий-ском языках, преимущественно в период 2011-2015 гг. Почка как орган-мишень и место деградации инкретиновых гормонов

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“…Dipeptyl peptidase-4 inhibitors selectively foster insulin secretion without inducing hypoglycemia, which might be advantageous in kidney transplant recipients with NODAT. Dipeptyl peptidase-4 inhibition (vildagliptin, sitagliptin) in kidney transplant recipients with overt NODAT was found to be safe and efficient, providing a novel treatment alternative for this specific form of diabetes [64][65][66] .…”

Section: Post-transplantation Managementmentioning

confidence: 99%

New-onset diabetes mellitus after renal transplantation

Goldmannová¹,

Karásek²,

Krystynik³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background and Aim. Diabetes mellitus is a very common metabolic disease with a rising incidence. It is both a leading cause of chronic renal disease and one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. The aim of this paper is to review current knowledge of NODAT including risk factors, diagnosis and management. Methods. A MEDLINE search was performed to retrieve both original and review articles addressing the epidemiology, risk factors, screening and management of NODAT. We also focused on microRNAs as potential biomarkers of NODAT. Results and Conclusion. Understanding the risk factors (both modifiable-e.g. obesity, viruses, and unmodifiable-e.g. age, genetics) may help reduce the incidence and impact of NODAT using pre-and post-transplant management. This can lead to better long-term graft function and general transplant success.

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Efficacy and Safety of Vildagliptin in New-Onset Diabetes After Kidney Transplantation—A Randomized, Double-Blind, Placebo-Controlled Trial

Cited by 101 publications

References 57 publications

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

Incretin-based therapy: renal effects

New-onset diabetes mellitus after renal transplantation

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