Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

“…This finding may be related to the self‐limiting nature of this mode of action: Efficacy decreases as hyperglycemia lessens 47. In line with previous reports, SGLT2 inhibitors were associated with increased risks of genital infections.…”

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

“…The primary cause of T2DM is obesity-driven IR in the liver, white adipose tissue (WAT), and skeletal muscle, combined with the relative insufficient secretion of insulin by pancreatic β cells [6]. At present, the available drugs for T2DM fall into four general categories: insulin, insulin secretagogues, insulin sensitizers, and prandial glucose regulators [7]. The drugs currently available have only limited efficacy, limited tolerability, and significant mechanism-based side effects.…”

The experience of Avicenna and possibility to improve the diabetes treatment

“…Тахрани и др. приводится анализ эффективности новейших современных препара-тов и обсуждаются механизмы их действия при СД 2-го типа по результатам изучения 359 опублико-ванных научных работ [1]. Авторы отмечают, что в большинстве исследований основные симптомы заболевания, такие как инсулинорезистентность, глюкозорезистентность, рассматриваются как ре-зультат недостаточности или нарушения функций β-клеток островков Лангерганса.…”

“…Авторы отмечают, что в большинстве исследований основные симптомы заболевания, такие как инсулинорезистентность, глюкозорезистентность, рассматриваются как ре-зультат недостаточности или нарушения функций β-клеток островков Лангерганса. Кроме того, выяв-лены проявления дисфункций многих органов при использовании наиболее популярных антидиабети-ческих лекарственных препаратов нового поколе-ния с разными механизмами гипогликемического действия и описано их влияние на уровень глюкозы в крови [1]. Так, например, контроль уровня глюкозы метформином при СД 2-го типа осуществляется че-рез печень и кишечник.…”