Glucagon-like peptide-1 receptor: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 18, 2024

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and found primarily on surfaces various cell types within human body. This specifically interacts with GLP-1, key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, several other crucial biological functions. In recent years, GLP-1 medications have become focal point medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, broad development prospects. article thoroughly traces developmental milestones drugs, from initial discovery clinical application, detailing evolution diverse along distinct pharmacological properties. Additionally, this paper explores potential applications agonists (GLP-1RAs) fields such neuroprotection, anti-infection measures, reduction inflammation, enhancement cardiovascular function. It provides in-depth assessment effectiveness GLP-1RAs across multiple body systems-including nervous, cardiovascular, musculoskeletal, digestive systems. includes integrating latest trial data delving into signaling pathways mechanisms. primary goal emphasize extensive benefits using treating spectrum diseases, obesity, non-alcoholic fatty liver disease (NAFLD), neurodegenerative musculoskeletal forms cancer. ongoing new indications for drugs offers promising prospects further expanding interventions, showcasing field.

Language: Английский

---

New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics

Annual Review of Medicine, Journal Year: 2023, Volume and Issue: 74(1), P. 125 - 139

Published: Jan. 27, 2023

Nearly half of Americans are projected to have obesity by 2030, underscoring the pressing need for effective treatments. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) represent first agents in a rapidly evolving, highly promising landscape nascent hormone-based therapeutics. With understanding neurobiology expanding, these emerging entero-endocrine and endo-pancreatic combined or coformulated with GLP-1 RAs herald new era targeted, mechanism-based treatment obesity. This article reviews previews imminent future nutrient-stimulated anti-obesity

Language: Английский

---

The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4334 - 4334

Published: April 14, 2022

Insulin resistance is documented in clamp studies 75% of women with polycystic ovary syndrome (PCOS). Although it not included the diagnostic criteria PCOS, there a crucial role this metabolic impairment, which along hormonal abnormalities, increase each other vicious circle PCOS pathogenesis. group patients results from defects at molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, reactive oxygen species. While lifestyle intervention has first-line prevention management excess weight anti-obesity pharmacological agents achieving maintaining loss being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) only act reducing body but also can affect mechanisms involved resistance, like an increasing expression glucose transporters insulin-dependent tissues, decreasing oxidative stress, modulating lipid metabolism. They tend to improve fertility either LH surge hypothalamus-pituitary inhibition due estrogen connected or too high levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment obese patients, acting on one primary causes level.

Language: Английский

---

Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide

Canadian Journal of Anesthesia/Journal canadien d anesthésie, Journal Year: 2023, Volume and Issue: 70(8), P. 1300 - 1306

Published: July 19, 2023

Language: Английский

---

Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort

Annals of the Rheumatic Diseases, Journal Year: 2023, Volume and Issue: unknown, P. ard - 223845

Published: May 31, 2023

Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated type 2 diabetes mellitus (T2DM) obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term.The Shanghai Osteoarthritis Cohort study prospective, observational, multicentre of >40 000 adults with clinically diagnosed aged >45 years Shanghai. We identified all participants comorbid T2DM enrolled 1 January 2011 to 2017. Primary outcome was incidence surgery after enrolment. Secondary outcomes included pain-relieving medication use, number intra-articular therapies, Western Ontario McMaster Universities Index (WOMAC) medial femorotibial joint cartilage thickness. To evaluate effects GLP-1RA, we performed before-and-after comparison who had no exposure.For an intergroup (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference change baseline -7.29 kg (95% CI -8.07 -6.50 kg), p<0.001) lower (93/1574 (5.9%) 4/233 (1.7%), adjusted p=0.014) were observed group. Statistically significant differences WOMAC total pain subscale scores score -1.46 -2.84 -0.08), p=0.038; subscore -3.37 -5.79 -0.94), p=0.007). Cartilage-loss velocity significantly group postadjustment characteristics -0.02 mm -0.03 -0.002 mm), p=0.004). For within group, decrease symptom-relieving consumption (after-treatment before-treatment: -0.03±0.05 -0.05±0.07 mm/year, p<0.001). The association between exposure decreased mediated by reduction (mediation proportion: 32.1%), instead glycaemic control (too small calculate).With sufficient treatment duration, might be disease-modifying T2DM, possibly loss. Further investigation needed elucidate on disease process, structure patient-reported osteoarthritis.

Language: Английский

---

Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis

BMJ Open, Journal Year: 2023, Volume and Issue: 13(3), P. e061807 - e061807

Published: March 1, 2023

Objective To compare the efficacy and safety between within glucagon-like peptide-1 receptor agonists (GLP-1RAs) sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in overweight or obese adults with without diabetes mellitus. Methods PubMed, ISI Web of Science, Embase Cochrane Central Register Controlled Trials database were comprehensively searched to identify randomised controlled trials (RCTs) effects GLP-1RAs SGLT-2is participants from inception 16 January 2022. The outcomes changes body weight, glucose level blood pressure. serious adverse events discontinuation due events. mean differences, ORs, 95% credible intervals (95% CI), surface under cumulative ranking evaluated for each outcome by network meta-analysis. Results Sixty-one RCTs included our analysis. Both conferred greater extents weight reduction, achieving at least 5% wt loss, HbA1c fasting plasma decrease compared placebo. was superior reduction (MD: −0.39%, CI −0.70 −0.08). had high risk events, while relatively safe. Based on intraclass comparison, semaglutide 2.4 mg among most effective interventions losing −11.51 kg, −12.83 −10.21), decreasing −1.49%, −2.07 −0.92) −2.15 mmol/L, −2.83 −1.59), reducing systolic pressure −4.89 mm Hg, −6.04 −3.71) diastolic −1.59 −2.37 −0.86) moderate certainty evidences, it associated Conclusions Semaglutide showed greatest controlling glycaemic PROSPERO registration number CRD42021258103.

Language: Английский

---

Role of Glucagon‐Like Peptide‐1 Receptor Agonists in Achieving Weight Loss and Improving Cardiovascular Outcomes in People With Overweight and Obesity

Journal of the American Heart Association, Journal Year: 2023, Volume and Issue: 12(11)

Published: June 6, 2023

Obesity remains a major public health problem, affecting almost half of adults in the United States. Increased risk cardiovascular disease (CVD) and CVD mortality are obesity‐related complications, management guidelines now recommend weight loss as key strategy for primary prevention patients with overweight or obesity. The recently demonstrated efficacy some pharmacologic therapies chronic may encourage care professionals to recognize obesity treatable serious motivate re‐engage when previous attempts have been ineffective unsustainable. This review article summarizes benefits challenges associated lifestyle changes, bariatric surgery, historical interventions treatment obesity, focuses on current evidence safety newer glucagon‐like peptide‐1 receptor agonist medications potential reduction risk. We conclude that available demonstrates agonists should be strongly considered clinical practice people type 2 diabetes. If ongoing research proves effective reducing onset irrespective diabetes status, it will herald new paradigm this setting, is time better these agents.

Language: Английский

---

Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(4), P. 689 - 703

Published: April 29, 2024

Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC preventable with about 70% attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting factors HCC. Here we evaluate the association GLP-1RAs incident in real-world population.

Language: Английский

---

Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 199 - 199

Published: Feb. 2, 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used diabetes and obesity medications but have been associated with gastrointestinal (GI) adverse events. However, real-world evidence on comparative GI reaction profiles is limited. Objectives: This study aimed to evaluate events among GLP-1 RA users compare semaglutide, dulaglutide, liraglutide, exenatide safety regarding the profile. Methods: retrospective cross-sectional analysis utilized data 10,328 adults diabetes/obesity in National Institutes of Health All Us cohort. New were identified, examined. Logistic regression determined factors Results: The mean age population was 61.4 ± 12.6 years, 65.7% female, 51.3% White, they had a high comorbidity burden. Abdominal pain (57.6%) most common event, followed by constipation (30.4%), diarrhea (32.7%), nausea vomiting (23.4%), bleeding (15.9%), gastroparesis (5.1%), pancreatitis (3.4%). Dulaglutide liraglutide higher rates abdominal pain, constipation, diarrhea, than semaglutide exenatide. Liraglutide highest (4.0% 3.8%, respectively). Compared dulaglutide odds vomiting. They also semaglutide. No significant differences existed or risks between RAs. Conclusions: In this cohort, Differences agents, appearing safer other RAs, except for gastroparesis. These findings can inform selection considering risk factors. Further studies needed causal relationship concomitant medication use.

Language: Английский

---

Revised definition of obesity in Asian Indians living in India

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102989 - 102989

Published: Jan. 1, 2025

Language: Английский

---