scholarly journals A Nephrologist Perspective on Obesity: From Kidney Injury to Clinical Management

2021 ◽  
Vol 8 ◽  
Author(s):  
Clara García-Carro ◽  
Ander Vergara ◽  
Sheila Bermejo ◽  
María A. Azancot ◽  
Joana Sellarés ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Injury ◽  
Glucose Lowering ◽  
New Frontier ◽  
All Cause Mortality ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
Angiotensin Blockade

Obesity is one of the epidemics of our era. Its prevalence is higher than 30% in the U.S. and it is estimated to increase by 50% in 2030. Obesity is associated with a higher risk of all-cause mortality and it is known to be a cause of chronic kidney disease (CKD). Typically, obesity-related glomerulopathy (ORG) is ascribed to renal hemodynamic changes that lead to hyperfiltration, albuminuria and, finally, impairment in glomerular filtration rate due to glomerulosclerosis. Though not only hemodynamics are responsible for ORG: adipokines could cause local effects on mesangial and tubular cells and podocytes promoting maladaptive responses to hyperfiltration. Furthermore, hypertension and type 2 diabetes mellitus, two conditions generally associated with obesity, are both amplifiers of obesity injury in the renal parenchyma, as well as complications of overweight. As in the native kidney, obesity is also related to worse outcomes in kidney transplantation. Despite its impact in CKD and cardiovascular morbility and mortality, therapeutic strategies to fight against obesity-related CKD were limited for decades to renin-angiotensin blockade and bariatric surgery for patients who accomplished very restrictive criteria. Last years, different drugs have been approved or are under study for the treatment of obesity. Glucagon-like peptide-1 receptor agonists are promising in obesity-related CKD since they have shown benefits in terms of losing weight in obese patients, as well as preventing the onset of macroalbuminuria and slowing the decline of eGFR in type 2 diabetes. These new families of glucose-lowering drugs are a new frontier to be crossed by nephrologists to stop obesity-related CKD progression.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

2021 ◽  
Vol 104 (11) ◽  
pp. 1850-1865
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Evidence Review ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Lowering Therapy ◽  
The Cost ◽  
Selection Of

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

scholarly journals Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

2003 ◽  
Vol 31 (3) ◽  
pp. 529-540 ◽  
Author(s):  
BD Green ◽  
VA Gault ◽  
MH Mooney ◽  
N Irwin ◽  
CJ Bailey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Biological Activities ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Glucose Lowering ◽  
Dpp Iv ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

scholarly journals Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes

Heart ◽  
2016 ◽  
Vol 102 (19) ◽  
pp. 1581-1587 ◽  
Author(s):  
Uchenna Anyanwagu ◽  
Jil Mamza ◽  
Rajnikant Mehta ◽  
Richard Donnelly ◽  
Iskandar Idris
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
All Cause Mortality ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals The role of metformin in the light of the most recent Guidelines

2020 ◽  
Vol 23 (1) ◽  
pp. 61
Author(s):  
Corigliano, G.
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Newly Diagnosed ◽  
High Cardiovascular Risk ◽  
Glucose Lowering ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Moment

Metformin was introduced in the market about 60 years ago and is definitely the most used drug in people with type 2 diabetes mellitus at the moment. In fact, it has insulin-sensitizing properties, through which it provides not only doubtless glucose lowering effects but also some protection against ADRD and cancer and especially significant cardiovascular benefits. We hereby briefly review the literature behind the above mentioned extra-glycemic effects and, based on expected additional benefits, suggest to refrain from delaying metformin utilization in addition to first class drugs like inhibitors of type 2 sodiumglucose cotransport (SGLT-2i) and /or glucagon-like peptide 1 receptor agonists (GLP1-RA) in people at high cardiovascular risk with newly diagnosed type 2 diabetes. KEY WORDS metformin; diabetes mellitus; cardiovascular disease; ADRD; cancer

Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases

2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 73-80 ◽  
Author(s):  
Francesco Prattichizzo ◽  
Lucia La Sala ◽  
Lars Rydén ◽  
Nikolaus Marx ◽  
Marc Ferrini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Receptor Agonist ◽  
Glucose Lowering ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications. Recent cardiovascular outcome clinical trials suggest that certain new glucose-lowering drugs are accompanied by additional cardioprotective properties. Indeed, selected glucagon-like peptide-1 receptor agonists have a proved cardiovascular benefit in terms of a reduced incidence of ischaemic events, while sodium/glucose co-transporter-2 inhibitors have also shown significant protection, with a striking effect on heart failure and renal endpoints. These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages. Furthermore, the new 2019 European Society of Cardiology guidelines in collaboration with the European Association for the Study of Diabetes recommend a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor in treatment-naive patients with type 2 diabetes mellitus with pre-existing cardiovascular disease or at high cardiovascular risk. Future research will disentangle the mechanisms underpinning these beneficial effects and will also establish to what extent these results are generalisable to the whole diabetes population. In the meantime, available evidence should prompt a wide diffusion of these two classes of drugs among patients with diabetes and cardiovascular disease. Here, we briefly summarise recent findings emerging from cardiovascular outcome clinical trials, discuss their impact on treatment algorithms and propose new possible approaches to improve our knowledge further regarding the cardiovascular effect of glucose-lowering medications.

scholarly journals GLP-1 Receptor Agonists in Type 2 Diabetes and Beyond – New Insights 2015

2015 ◽  
Vol 11 (1) ◽  
pp. 21 ◽  
Author(s):  
Baptist Gallwitz ◽  
Keyword(s):  
Type 2 Diabetes ◽  
European Association ◽  
The Novel ◽  
Diabetes Therapy ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
Long Acting

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were introduced for type 2 diabetes therapy nearly 10 years ago, among them short-acting compounds on the basis of the GLP-1-like peptide exendin-4 (exenatide and lixisenatide) and a long-acting GLP-1 RA based on the human GLP-1 sequence (liraglutide). Recently, two novel long-acting GLP-1 RAs on the basis of human GLP-1 sequence, for onceweekly application, have been approved for therapy of type 2 diabetes. Additionally, liraglutide has been approved for treatment of obesity at a higher dose than that used for diabetes therapy. This mini-review gives a short overview of the novel long-acting GLP-1 RAs albiglutide and dulaglutide and also reviews the studies of liraglutide in treatment of obesity leading to its approval for this use. These studies were largely presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in fall 2014.

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