Clinical Pharmacology of Dipeptidyl Peptidase 4 Inhibitors: Comparative Review

Sidorov, A.V. Sidorov

doi:10.33978/2307-3586-2020-16-25-24-48

Cited by 5 publications

(1 citation statement)

References 89 publications

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“…Антиатеросклеротические свойства иДПП-4 могут быть связаны с противовоспалительной активностью, улучшением эндотелиальной функции, влиянием на метаболизм липидов [23] [24,25]. Прием саксаглиптина в отличие от трех других иДПП-4 ассоциировался с небольшим, но статистически значимым увеличением частоты госпитализаций по поводу хронической сердечной недостаточности при сравнении с плацебо [26]. В настоящее время 2 класса сахароснижающих препаратов рассматриваются как препараты с доказанными нефрои кардиопротективными свойствами: ингибиторы натрийглюкозного котранспортера 2-го типа (НГЛТ-2) и агонисты рецепторов глюкагоноподобного пептида-1 (аГПП-1).…”

Section: лечение днunclassified

Diabetic nephropathy: what should cardiologist remember

Trubitsyna¹,

Зайцева²,

Severina³

2021

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Prevalence of diabetes mellitus (DM) progressively increases around the world. Diabetic nephropathy (DN) is significant reason of end-stage renal disease and it is associated with high risk of cardiovascular disease and mortality. Necessity of expensive renal replacement therapy for patients with prominent vascular diabetic complications and end-stage renal disease has significant socio-economic impact. DM, as a one of leading causes of kidney diseases, competes for stricted resources of public health. Renal replacement therapy in patients with DM does not solve the whole problem, because survival of such patients is low, comparing with another kidney diseases, first of all because of cardiovascular diseases. Good control of glycaemia, blood pressure and cholesterol level and prescription of renin-angiotensin-aldosterone system inhibitors and statins decrease cardiovascular risk and slow down DN progression, as it was shown in many clinical trials. So patients with DM and DN should receive complex therapy for risk reduction of kidney disease and cardiovascular disorders progression. Keywords: diabetes mellitus type 2, diabetic nephropathy, nephroprotection, cardioprotection, SGLT-2 inhibitors, GLP-1 agonists, renin-angiotensin-aldosterone system For citation: Trubitsyna NP, Zaitseva NV, Severinа AS. Diabetic nephropathy: what should cardiologist remember. Consilium Medicum. 2021; 23 (1): 20–24. DOI: 10.26442/20751753.2021.1.200712

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Section: лечение днunclassified

Diabetic nephropathy: what should cardiologist remember

Trubitsyna¹,

Зайцева²,

Severina³

2021

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Hypoglycemic Effect of Sitagliptin and Aminoguanidine Combination in Experimental Diabetes Mellitus

Куркин

Бакулин

Морковин

et al. 2023

Farm. farmakol. (Pâtigorsk)

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The aim of the work was to determine the antidiabetic effect of a sitagliptin and aminoguanidine combination in rats with experimental diabetes mellitus.Materials and methods. The study was carried out on male Wistar rats and C57BL/KsJ-db/db mice. According to the models used, it was divided into 4 series, in which alloxan, steroid-induced (dexamethasone) and streptozotocin-nicotinamide-induced diabetes mellitus (DM) were formed, respectively, in rats, and in the 4 series, obese C57BL/KsJ-db/db mice were used. In the 1 and 2 series, the treatment was started prophylactically – 3 h after the alloxan administration and simultaneously with the dexamethasone administration, in the 3rd and 4th series, the treatment was carried out after the pathology had developed – 7 days after the streptozotocin with nicotinamide administration, and in the obese mice – immediately after their distribution according to the groups. The treatment was carried out with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The treatment was continued till the end of the experiment, which was completed with an oral glucose tolerance test (OGTT) after 4 h of fasting. The obtained data were subjected to statistical processing.Results. In the course of the experiments, it was found out that the prophylactic administration of a sitagliptin and aminoguanidine combination, unlike each of the components, prevented the development of alloxan DM. More effectively than the administration of sitagliptin alone, it reduced the severity of steroid-induced DM, which was expressed in a significantly lower level of fasting glycemia (after 4 h of fasting) and postprandial glycemia (during OGTT). Under the conditions of streptozotocin-nicotinamide-induced DM, the studied combination slowed down the progression of the pathology, and in the obese mice, the course therapeutic administration of sitagliptin and its combination reduced the severity of carbohydrate metabolism disorders (fasting glycemia) and increased the rate of glucose utilization.Conclusion. As an iNOS blocker, aminoguanidine enhances the antidiabetic effect of sitagliptin, preventing the development of alloxan diabetes and reducing the severity of steroid-induced DM when administered prophylactically. When administered therapeutically, it reduces the severity of streptozotocin-nicotinamide-induced DM in rats and type 2 DM in mice with a predisposition to obesity.

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Factors determining the clinical significance of dipeptidyl peptidase-4 inhibitors in the treatment of elderly patients with type 2 diabetes mellitus

et al. 2021

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Elderly patients with diabetes type 2 represent complex and heterogeneous group with different diabetes complications and comorbidity, polypharmacy, functional and cognitive state. Each of those factors should be taken into account to choose the best glycemic targets as well as the most tailored treatment so that it is necessary for endocrinologist to perform geriatric assessment. The most favorable antidiabetic drugs for elderly are safe in terms of hypoglycemia and cardiovascular risks, can be used irrespective of kidney function, do not affect weight or bone mineral density, and are available in fixed combinations with other drugs. Dipeptidyl pepti-dase-4 (DPP-4) inhibitors meet all these requirements with low adverse events rate. Interdisciplinary approach, close interaction with patient and his relatives and considerations for both intensification and deprescribing are keys to successful treatment in this patient subgroup. Cardiovascular events are the most common cause of death and hypoglycemia is highly unfavorable in elderly because it can lead to falls, life-threatening arrhythmias, and cognitive impairment. So deprescribing in elderly with diabetes should be primarily aimed at minimizing of cardiovascular events and severe hypoglycemia risks. For this purpose, it is considered to the reject use of sulfonylureas, glinides, insulins in favor of safer ones (metformin, GLP-1 receptor agonists, SGLT-2 inhibitors, DPP-4 inhibitors).

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Clinical Pharmacology of Dipeptidyl Peptidase 4 Inhibitors: Comparative Review

Cited by 5 publications

References 89 publications

Diabetic nephropathy: what should cardiologist remember

Diabetic nephropathy: what should cardiologist remember

Hypoglycemic Effect of Sitagliptin and Aminoguanidine Combination in Experimental Diabetes Mellitus

Factors determining the clinical significance of dipeptidyl peptidase-4 inhibitors in the treatment of elderly patients with type 2 diabetes mellitus

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