Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial

The Lancet Diabetes & Endocrinology, Journal Year: 2018, Volume and Issue: 6(8), P. 605 - 617

Published: June 14, 2018

Language: Английский

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Obesity, kidney dysfunction and hypertension: mechanistic links

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(6), P. 367 - 385

Published: April 23, 2019

Language: Английский

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Glucagon-like peptide 1 in health and disease

Nature Reviews Endocrinology, Journal Year: 2018, Volume and Issue: 14(7), P. 390 - 403

Published: May 4, 2018

Language: Английский

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Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function

Frontiers in Endocrinology, Journal Year: 2018, Volume and Issue: 9

Published: Nov. 23, 2018

The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its 'incretin effect' in restoring glucose homeostasis diabetics, however, it now apparent that has a broader range of physiological effects the body. Both vitro and vivo studies have demonstrated GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression influence neuroprotective pathways. A substantial body evidence accumulated with respect to how analogues act restore maintain normal cellular functions. These findings prompted several clinical trials which reported improve cardiac function, lung function reduce mortality patients obstructive disease, blood pressure lipid storage, even prevent synaptic loss neurodegeneration. Mechanistically, elicits via acute elevation cAMP levels, subsequent protein kinase(s) activation, pathways well defined pancreatic β-cells insulin secretion conjunction elevated Ca2+ ATP. More recently, new shed light on additional downstream stimulated by chronic exposure, direct relevance our understanding potential therapeutic longer lasting recently developed use. In this review, we provide comprehensive description diverse roles across multiple tissues, describe discuss novel pleiotropic applications treatment human disease.

Language: Английский

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Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial

The Lancet Diabetes & Endocrinology, Journal Year: 2018, Volume and Issue: 6(11), P. 859 - 869

Published: Oct. 3, 2018

Language: Английский

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Safety of Semaglutide

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: July 7, 2021

The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and only GLP-1RA currently available as both subcutaneous oral formulation. While GLP-1RAs effectively improve glycemic control cause weight loss, potential safety concerns have arisen over years. For semaglutide, such been addressed in extensive phase 3 registration trials including cardiovascular outcome for (SUSTAIN: Semaglutide Unabated Sustainability Treatment Type 2 Diabetes) (PIONEER: Peptide InnOvatioN Early diabEtes tReatment) are being studied further registries, real world data studies. In current review we discuss occurrence adverse events associated with focusing on hypoglycemia, gastrointestinal side effects, pancreatic (pancreatitis cancer), thyroid cancer, gallbladder events, aspects, acute kidney injury, diabetic retinopathy (DRP) complications injection-site allergic reactions where available, highlight underlying mechanisms. Furthermore, whether effects specific or a class effect. We conclude that induces mostly mild-to-moderate transient disturbances increases risk biliary disease (cholelithiasis). No unexpected issues to date, established profile similar other definitive conclusions cancer cannot be drawn at point due low incidence these conditions. Due its potent glucose-lowering effect, patients deterioration existing DRP should carefully monitored if treated particularly also insulin. Given beneficial metabolic actions severe has an overall favorable risk/benefit patient type diabetes.

Language: Английский

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Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): a randomised, double-blind, placebo-controlled trial

The Lancet Diabetes & Endocrinology, Journal Year: 2019, Volume and Issue: 7(6), P. 429 - 441

Published: April 13, 2019

Language: Английский

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SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA

Nephrology Dialysis Transplantation, Journal Year: 2019, Volume and Issue: 34(2), P. 208 - 230

Published: Jan. 25, 2019

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many these experience progression cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment type 2 DM have emerged, including inhibitors sodium-glucose co-transporter-2 (SGLT-2) glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, were reported to other beneficial effects systems, such as weight loss blood pressure reduction. Most importantly, contrast all studies anti-diabetic agents, series recent randomized, placebo-controlled outcome trials showed that SGLT-2 GLP-1 agonists are able reduce events all-cause mortality, well DM. This document presents detail available evidence on cardioprotective nephroprotective analogues, analyses potential mechanisms involved actions discusses their place CKD

Language: Английский

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SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management

Diabetes Care, Journal Year: 2018, Volume and Issue: 41(8), P. 1543 - 1556

Published: July 11, 2018

The progressive nature of type 2 diabetes (T2D) requires practitioners to periodically evaluate patients and intensify glucose-lowering treatment once glycemic targets are not attained. With guidelines moving away from a one-size-fits-all approach toward setting patient-centered goals allowing flexibility in choosing second-/third-line drug the growing number U.S. Food Drug Administration–approved agents, keen personalized management T2D has become challenge for health care providers daily practice. Among newer generation classes, sodium–glucose cotransporter inhibitors (SGLT2is), which enhance urinary glucose excretion lower hyperglycemia, have made an imposing entrance armamentarium. Given their unique insulin-independent mode action favorable efficacy–to–adverse event profile given marked benefits on cardiovascular-renal outcome moderate-to-high risk patients, led updates product monographs, role this class multidrug regimes is promising. However, despite many speculations based pharmacokinetic pharmacodynamic properties, physiological reasoning, potential synergism, effects these agents terms pleiotropic efficacy when combined with other classes largely understudied. In perspective, we review currently emerging evidence, discuss prevailing hypotheses, elaborate necessary future studies clarify risks using SGLT2i dual combination metformin triple glucagon-like peptide 1 receptor agonist, dipeptidyl peptidase 4 inhibitor, or agent that recommended by American Diabetes Association European Study (i.e., sulfonylurea, thiazolidinedione, insulin) treat T2D.

Language: Английский

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Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER

Circulation, Journal Year: 2021, Volume and Issue: 145(8), P. 575 - 585

Published: Dec. 14, 2021

We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes.

Language: Английский

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