The potential for renoprotection with incretin-based drugs

Tanaka, Tetsuhiro; Higashijima, Yoshiki; Wada, Takehiko; Nangaku, Masaomi

doi:10.1038/ki.2014.236

Cited by 116 publications

(93 citation statements)

References 104 publications

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“…Конечные продукты гликирования (КПГ) индуцируют развитие окислительного стресса, системно-го воспаления, фиброза, апоптоза в культуре мезангиаль-ных клеток за счет активации таких агентов, как фактор роста эндотелия сосудов, MCP-1 [31]. В эксперименталь-ных работах продемонстрировано ингибирующее влия-ние ГПП-1 на экспрессию МСР-1 и рецептора КПГ в культуре мезангиальных клеток, ингибирование процес-сов системного воспаления и окислительного стресса [32,33]. В экспериментах на лабораторных крысах с СД-1 применение эксендина-4 способствовало уменьшению альбуминурии, гипертрофии клубочков, макрофагальной инфильтрации клубочков, снижению развития фиброза и тубулопатии вне зависимости от уровня глюкозы в крови [34].…”

Section: Discussionunclassified

Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease

Arutyunova¹,

Глазунова²,

Михалева³

et al. 2015

Ter. arkh.

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РезюмеЦель исследования. Изучить негликемические эффекты инкретинов у больных сахарным диабетом 1-го типа (СД-1) дли-тельного течения (более 20 лет) и хронической болезнь почек. Материалы и методы. Обследовали 75 пациентов с различной степенью выраженности диабетической нефропатии (ДН) и без ДН, включая больных, получающих заместительную почечную терапию программным гемодиализом, и пациентов, перенесших трансплантацию почки. Помимо общепринятых методов обследования проводили оценку показателей фос-форно-кальциевого обмена (кальций, фосфор, паратгормон, витамин D и фактор роста фибробластов 23-го типа -FGF-23), маркера патологии сердца -предсердного натрийуретического пептида, маркеров провоспалительного статуса (моноцитарного хемоаттрактантного протеина 1-го типа -MCP-1, С-реактивный белок -СРБ) и фиброза (трансформи-рующий β-фактор роста), определение уровня глюкагоноподобного пептида 1-го типа (ГПП-1) и глюкозозависимого инсу-линотропного пептида (ГИП). Всем больным выполнена мультиспиральная компьютерная томография сердца с расчетом индекса Агатстона (кальциевой индекс -КИ), отражающего степень кальцификации коронарных артерий. Результаты. По данным исследования, зависимость уровня ГПП-1 и ГИП от наличия и степени выраженности ДН у паци-ентов обследуемых групп не выявлена. Отмечена обратная взаимосвязь ГПП-1 с возрастом пациентов, что указывает на снижение секреции этого пептида у лиц старшего возраста. Получены данные о положительном влиянии ГПП-1 на липидный состав крови (общий холестерин: r=-0,320; p<0,05) и выраженность кальцификации коронарных артерий (КИ: r=-0,308; p<0,05). Отмечено разнонаправленное влияние ГИП на провоспалительные факторы: фибриноген (r=-0,264; p<0,05), СРБ (r=-0,626; p<0,05) и FGF-23 (r=-0,341; p<0,05). Заключение. Продемонстрировано наличие негликемических эффектов инкретинов, благоприятно влияющих на патоге-нетические процессы, которые лежат в основе поздних осложнений СД-1. Полученные данные указывают на потенциаль-ную эффективность препаратов, основанных на действии инкретинов, в профилактике и лечении поздних осложнений СД, что определяет необходимость проведения более крупных исследований. Ключевые слова: сахарный диабет 1-го типа, глюкагоноподобный пептид 1-го типа, глюкозозависимый инсулинотропный пептид, хроническая болезнь почек.Aim. To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease. Subjects and methods. Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and th...

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Section: Discussionunclassified

Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease

Arutyunova¹,

Глазунова²,

Михалева³

et al. 2015

Ter. arkh.

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“…DPP-4 inhibits hemopoietic factors such as G-CSF or erythropoietin, and it has been reported that the antagonism is inhibited by a DPP-4 inhibitor [16][17][18]. Several reports suggest that DPP-4 inhibitors have antiinflammatory effects and can improve bone marrow function [45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Also, it is hard to cause the weight gain too [9]. It has been reported to exert a kidney protection effect and is expected as the new drug of choice in diabetes treatment where there is decreased renal function [10][11][12][13][14][15][16]. Recently, DPP-4 inhibits hemopoietic factors such as granulocyte-colony stimulating factor (G-CSF) or erythropoietin, and it is reported that the antagonism is inhibited by DPP-4 inhibitors [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Saxagliptin versus Mitiglinid in patients with type 2 diabetes and end-stage renal disease

Sakai

Sakai²,

Mugishima

et al. 2017

Ren Replace Ther

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Background: There are very few oral antidiabetic drugs recommended for patients on dialysis. Saxagliptin is known for its potent effect and long duration of action. In this study, we compared the efficacy of Saxagliptin with Mitiglinid for diabetes control and renal anemia in hemodialysis patients with type 2 diabetes mellitus. Methods: We performed a 6-month prospective, open-label, parallel group study of 41 patients with type 2 diabetes mellitus undergoing hemodialysis who took alpha-glucosidase inhibitors or meglitinides and did not use insulin. Saxagliptin and Mitiglinid were administered at 2.5 and 5 mg/day, respectively. The primary outcomes were changes in hemoglobin A1c (HbA1c) and glycated albumin (GA). Other efficacy assessments included changes in Hb, darbepoetin alpha (DA) dose, and erythropoietin responsiveness index (ERI). Results: No patient required an increase in Saxagliptin or Mitiglinid dose, and there were no cases of hypoglycemia with symptoms. HbA1c and GA values were not significantly different between both groups. For HbA1c, the gradient of the regression line of the Saxagliptin and Mitiglinid groups were Y = −7.144e-005*X + 6.023 and Y = −0. 02604*X + 6.292, respectively, and no significant difference was found (p = 0.3281). However, for GA, the regression line of the Saxagliptin group significantly decreased (Y = −0.5036*X + 19.34 and Y = −0.2346*X + 18.79, p = 0.0371). Both groups did not have a significant change in the DA dose through the observation period. However, the DA dose of the Saxagliptin group significantly decreased when we compared the regression lines (Y = −0.8304*X + 21. 06 and Y = 0.6286*X + 16.12, p = 0.0019) of both groups. Furthermore, ERI did not change significantly but showed a significant difference when regression lines were compared (Y = −0.2030*X + 6.654 and Y = 0.1116*X + 5.288, p = 0.0082).

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“…It is uncertain whether this finding relates to the direct effects of liraglutide on kidney function. 21,22 More patients in the liraglutide group than in the placebo group permanently discontinued the trial regimen owing to adverse events (difference, 2.2 percentage points). There has been considerable interest in a potential association between the use of GLP-1-receptor agonists and pancreatitis and pancreatic cancer, although there is no consistent preclinical, pharmacovigilance, or epidemiologic evidence to date.…”

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confidence: 99%

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

2016

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BACKGROUNDThe cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODSIn this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTSA total of 9340 patients underwent randomization. The median follow-up was 3.8 years. ) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P = 0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONSIn the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.) a bs tr ac t

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The potential for renoprotection with incretin-based drugs

Cited by 116 publications

References 104 publications

Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease

Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease

Efficacy of Saxagliptin versus Mitiglinid in patients with type 2 diabetes and end-stage renal disease

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

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