Evolution of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

Galstyan, Gagik R.; Karataeva, Evgeniya A.; Yudovich, Ekaterina A.

doi:10.14341/dm8804

Cited by 9 publications

(6 citation statements)

References 54 publications

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“…MnSOD mRNA expression, reduced in the HFD-L group, is known to be down regulated with GLP-1RA therapy, and may re ect a reduced requirement of antioxidant activity from liraglutide [49]. InR expression was lowest in the HFD-L, but not HFD-C group, most likely because of the known greater e cacy GLP-1RAs have on insulin receptor activity, glucose uptake and insulin resistance [50]. Interestingly, neither method of preconception weight loss made any appreciable difference to preconception brotic markers in the kidney.…”

Section: Discussionmentioning

confidence: 95%

Kidney outcomes are altered by preconception weight modulation in rodent mothers with obesity

Rodrigo,

Chen,

Pollock

et al. 2023

Preprint

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Obesity increases the risk of chronic kidney disease in the mother. We have previously demonstrated the benefits of preconception maternal weight loss on fertility and pregnancy outcomes in a mouse model of maternal obesity. In this study, we aimed to determine if preconception weight loss, either by diet modification or the glucose-like peptide 1 agonist liraglutide, improves maternal kidney outcomes in late gestation. C57BL/6 female mice were fed either a high-fat-diet (HFD) or a standard chow (control) diet for 8 weeks. To induce pre-pregnancy weight loss, HFD-fed dams were either switched to a chow diet pre-pregnancy (4 weeks before mating, HFD-C) or administered liraglutide (0.3mg/kg subcutaneous, for 4weeks) whilst continuing on HFD (HFD-L). Liraglutide was discontinued one week prior to mating. HFD-V mice continued on HFD, with saline injections. Finally, a group of HFD-fed dams were ‘diet switched’ to a chow diet after conception (i.e., post-conception, HFD-PC). Maternal body weight and glucose tolerance were measured at two time points: prior to pregnancy and during late gestation followed by blood, urine and kidney collection. Serum creatinine, urinary creatinine and albumin, and kidney tissue gene expression and protein were measured. In the preconception period, the HFD-L and HFD-C mothers had lower urine albumin: creatinine ratios (UACR) and fatty acid synthase (FAS) protein expression (both P < 0.005 vs HFD-V). At late gestation, the kidneys of HFD-V and HFD-PC dams had increased gene expression of insulin receptor and FAS (both P < 0.05) and higher UACR compared to controls (P < 0.01). In the HFD-PC group, the kidneys showed increased mRNA and protein expression of metabolic and oxidative stress markers (FAS, 8-OHdG vs control, P < 0.05, P < 0.0001 respectively). The preconception intervention groups with liraglutide, or diet change showed reduced renal oxidative stress markers (protein expression of 8-OHdG, P < 0.05 vs HFD), mRNA and protein expression of FAS (P < 0.05 vs HFD), protein expression of fibrosis markers (collagen IV, fibronectin vs HFD, P < 0.05), and UACR (P < 0.05 vs HFD). Preconception weight loss benefits maternal kidney health during pregnancy, superior to diet intervention once pregnancy is established. This study suggests that pre-pregnancy weight reduction is necessary to optimise kidney outcomes in maternal obesity.

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Section: Discussionmentioning

confidence: 95%

Kidney outcomes are altered by preconception weight modulation in rodent mothers with obesity

Rodrigo,

Chen,

Pollock

et al. 2023

Preprint

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“…This release can be rapid, with a peak at 10 min post-initial glucose stimulus, followed by a sustained release from major insulin granules (approximately 90–95%) lasting up to 60 min under normal conditions ( 15 , 31 ). However, the low half-life of GLP-1 incretin could affect this process in individuals with DM2 or obesity ( 32 , 33 ). Therefore, GLP-1RA drugs like liraglutide or semaglutide can counteract DPP-4 degradation, prolonging the GLP-1R signal and maintaining insulin secretion via the mTOR-dependent HIF-1α pathway ( 34 ).…”

Section: Molecular Mechanisms Of Semaglutide and Liraglutidementioning

confidence: 99%

Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity

Tamayo-Trujillo,

Ruiz-Pozo,

Cadena-Ullauri

et al. 2024

Front. Nutr.

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Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing global prevalence of obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide and liraglutide, designed for type 2 diabetes mellitus treatment, have been explored as drugs for the treatment of obesity. This minireview describes the molecular mechanisms of semaglutide and liraglutide in different metabolic pathways, and its mechanism of action in processes such as appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, and lipid metabolism. Finally, several clinical trial outcomes are described to show the safety and efficacy of these drugs in obesity management.

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“…По данным другого метаанализа выявлено, что уменьшение массы у пациентов по сравнению с инсулинотерапией при использовании АР ГПП-1 длительного действия обычно меньше, чем при применении АР ГПП-1 короткого действия [38]. Результат систематического обзора (но с ограниченным метаанализом) продемонстрировал, что АР ГПП-1, вводимые 1 р/нед, в большинстве случаев более эффективны, чем эксенатид, вводимый 2 р/сут, в отношении снижении уровня HbA 1c и глюкозы плазмы натощак, при аналогичном воздействии на динамику массы тела (см.…”

Section: агонисты рецепторов глюкагоноподобного пептида-1unclassified

“…табл. 1) [38]. Таким образом, обобщенные данные метаанализов продемонстрировали, что терапия АР ГПП-1 1 р/нед способствует клинически значимому улучшению контроля гликемии, чем большая часть АР ГПП-1 короткого действия.…”

Section: агонисты рецепторов глюкагоноподобного пептида-1unclassified

Diabetes and obesity. The role of agonists glucagon-like peptide-1 of in the treatment of type 2 diabetes

Александровна¹,

Эдуардовна²

2018

Diabetes mellitus

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Significant number of patients with type 2 diabetes mellitus are obese. It is known that even glucose intolerance, as well as diabetes, can lead to vascular complications. At the same time, weight loss can reduce the risk of type 2 diabetes in obese and pre-diabetic patients. According to available data, a significant decrease in the incretin effect is observed in patients with type 2 diabetes and obese individuals. Thus, a decrease in the incretin effect leads to a violation of the insulin response to the intake of carbohydrates, and, consequently, an increase in the level of glucose in the blood. It was also found that the decrease in the incretin effect in patients with type 2 diabetes can be associated with a lower secretion of glucagon-like peptide-1. The interest is represented by groups of antidiabetic drugs capable of regulating glycemia by affecting the secretion of insulin and glucagon, depending on its level. Such drugs include glucagon-like peptide-1 receptor agonists. The article shows the advantage of prolonged action in patients with type 2 diabetes and obesity of the glucagon-like peptide 1 receptor agonists (albiglutide, dulaglutide, exenatide with slow release) dosing 1 time a week.

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Evolution of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

Cited by 9 publications

References 54 publications

Kidney outcomes are altered by preconception weight modulation in rodent mothers with obesity

Kidney outcomes are altered by preconception weight modulation in rodent mothers with obesity

Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity

Diabetes and obesity. The role of agonists glucagon-like peptide-1 of in the treatment of type 2 diabetes

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