A 2-Years Comparative Analysis of Tirzepatide, Semaglutide, Qsymia, Contrave, and Phentermine on Ocular Health in Individuals with Obesity: A Propensity-Score Matched Cohort Study DOI Creative Commons
Pen‐Hua Su, Yu‐Nan Huang,

Jo-Ching Chen

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract This landmark propensity-score matched study examined ocular outcomes of modern anti-obesity medications in nearly 5 million non-diabetic individuals with obesity. Through analysis TriNetX US network data, we discovered that Tirzepatide significantly reduced cataract risk versus other treatments, showing a striking 59% lower compared to Semaglutide (HR: 0.41, 95% CI: 0.19–0.85). users experienced markedly fewer visual disturbances than those on Contrave 0.58, 0.41–0.82) or Phentermine 0.62, 0.46–0.82). Both GLP-1 receptor agonists demonstrated protection against age-related cataracts, exceptional benefits 0.17, 0.07–0.42). While these protective effects remained robust across patient subgroups, Tirzepatide's diminished impaired kidney function. Multiple sensitivity analyses and negative controls validated compelling findings.

Language: Английский

Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretionin vitroandin vivoof a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001 DOI Creative Commons
Yusman Manchanda, Ben Jones, Gaëlle Carrat

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract The use of incretin analogues has emerged in recent years as an effective approach to achieve both enhanced insulin secretion and weight loss type 2 diabetes (T2D) patients. Agonists which bind stimulate multiple receptors have shown particular promise. However, off target effects, including nausea diarrhoea, remain a complication using these agents, modified versions with optimized pharmacological profiles and/or biased signaling at the cognate are increasingly sought. Here, we describe synthesis properties molecule binds glucagon-like peptide-1 (GLP-1) glucose-dependent insulinotropic polypeptide (GIP) (GLP-1R GIPR) enhance secretion. HISHS-2001 shows increased affinity GLP-1R, well tendency towards reduced internalization recycling this receptor versus FDA-approved dual GLP-1R/GIPR agonist tirzepatide. also displayed significantly greater bias cAMP generation β-arrestin recruitment compared In contrast, G αs was lower tirzepatide but higher GIPR. Administered obese hyperglycaemic db/db mice, circulating whilst lowering body HbA1c similar efficacy substantially doses. Thus, represents novel improved profile.

Language: Английский

Citations

1
Comparative Efficacy and Safety of GLP-1 Receptor Agonists for Weight reduction: A Model-Based Meta-Analysis of Placebo-Controlled Trials DOI Creative Commons
Hongquan Guo, Juan Yang, Jihan Huang

et al.

Obesity Pillars, Journal Year: 2025, Volume and Issue: unknown, P. 100162 - 100162

Published: Jan. 1, 2025

Obesity is a global epidemic. The FDA has approved glucagon-like peptide-1 (GLP-1) receptor agonists such as Liraglutide, Semaglutide, and the GLP-1/gastric inhibitory polypeptide (GIP) dual agonist Tirzepatide for treatment of obesity. Clinical trials GLP-1/GIP/glucagon(GCG) triple are ongoing. This study compared efficacy safety profiles different GLP-1 (GLP-1RAs) weight reduction explored related influencing factors, providing quantitative information development GLP-1RAs their clinical use. systematic review public databases included placebo-controlled randomized GLP-1RAs. Time-course, dose-response, covariate models were used to describe characteristics factors Subgroup analyses performed explore differences in specificity. Meta-analyses incidence adverse event dropout rates among Fifty-five studies involving 16,269 participants 12 included. Six drugs showed significant dose-response relationships. maximum effect ranged from 4.25 kg (Liraglutide) 22.6 (Retatrutide). Reported onset times 6.4 weeks (Orforglipron) 19.5 (Tirzepatide). At 52 weeks, effects 7.03 kg, 11.07 24.15 mono-agonists, dual-agonists, tri-agonists, respectively. There was negative correlation exponential pattern between age effect, whereas baseline BMI had no impact. Common events GLP-1RAs, reported literature include nausea, vomiting, diarrhea, constipation, with significantly higher nausea than that placebo. provides evaluation offers valuable insights into assessment new reduction.

Language: Английский

Citations

1
Impact of GLP‐1 Receptor Agonists on Alcohol‐Related Liver Disease Development and Progression in Alcohol Use Disorder DOI Open Access

Chia‐Chih Kuo,

Chun‐Hsien Li, Min‐Hsiang Chuang

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in reducing alcohol consumption, but their impact on clinical outcomes patients with use disorder (AUD) remains unclear. We investigated the association between GLP-1RAs and development progression of alcohol-related liver disease (ArLD) AUD. Using TriNetX Research Network, we conducted two retrospective cohort studies comparing versus dipeptidyl peptidase-4 inhibitors (DPP-4is) type 2 diabetes. The first included AUD without ArLD (n = 7132 after propensity score matching), while second comprised established 1896 matching). Primary were incident hepatic decompensation cohort. In (median follow-up: 63.2 months), GLP-1RA users showed significantly lower risks developing compared to DPP-4i (incidence rate: 6.0 vs. 8.7 per 1000 person-years; HR: 0.62, 95% CI: 0.44-0.87, p 0.006). also associated reduced all-cause mortality (HR: 0.53, < 0.001). 28.2 demonstrated 39.5 51.4 0.66, 0.51-0.85, 0.001) users. progressing AUD, suggesting potential therapeutic benefits this population.

Language: Английский

Citations

1
The potential role of GLP‐1 receptor agonists in osteoarthritis DOI Open Access

M P Ryan,

Saige Megyeri,

Wesley Nuffer

et al.

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Abstract Osteoarthritis (OA) is the most common form of arthritis, affecting over 500 million people globally. Current treatments are primarily symptom‐focused, with no approved therapies to halt disease progression. Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), widely used in type 2 diabetes (T2D) and obesity, demonstrate significant weight loss glucose‐lowering effects have been shown possess anti‐inflammatory properties. Given central role inflammation metabolic dysfunction OA, this review examines potential utility GLP‐1 RAs OA management, focusing on both indirect effects, such as reduction, possible direct inflammatory pathways cartilage preservation. Clinical studies suggest that may benefit by reducing weight, improving glycemic control, modulating markers relevant Notable findings include pain reduction knee (KOA) treated semaglutide STEP‐9 trial. In other studies, lower oxidative stress pro‐inflammatory cytokines, tumor necrosis factor (TNF‐α) interleukin (IL)‐6, reductions OA‐related functional impairment observed some cohorts. However, results vary, showing limited potentially linked degree achieved. Although report variability relief, likely influenced achieved, overall promise symptoms associated This emerging evidence supports a disease‐modifying option for offering dual joint health. Future research should focus establishing long‐term efficacy safety elucidating mechanism which influence pathology.

Language: Английский

Citations

1
Semaglutide and non‐arteritic anterior ischaemic optic neuropathy: Review and interpretation of reported association DOI Creative Commons
A Amini, Steffen Hamann, Michael Larsen

et al.

Acta Ophthalmologica, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

This review covers a seminal study of the relation between exposure to glucagon-like peptide 1 (GLP-1) agonist semaglutide and incident non-arteritic anterior ischaemic optic neuropathy (NAION) in neuro-ophthalmology clinic setting, subsequent studies unselected populations, meta-analysis clinical trials pathophysiology disc retina that may help elucidate NAION patients with diabetes or obesity. In matched cohort patients, those treated using agents other than had rates, orders magnitude higher background population, presumably because referral patterns led enrichment populations at high risk NAION. With semaglutide, rates were 4.28 7.64 times for type 2 (T2D) obesity, respectively, onset was within 14 months treatment initiation, whereas non-semaglutide evenly distributed over 3 years follow-up. Of four health care registry studies, each covering more 100 000 two found relative three without one trend towards being associated only, statistically insignificant imbalances alternatives. The various GLP-1 receptor agonists versus placebo active comparator no significant difference Prior reports long-term glycaemia reduction early worsening retinopathy indicate promote such events proportion its antihyperglycaemic potency. association small, crowded discs, oedema peripapillary exudation suggests semaglutide-related result from changes perfusion lead venous dilation and, presumably, congestion during hypoglycaemia. Given retrospective nature epidemiological causality cannot be inferred, but cautious approach use powerful glycaemia-reducing seems warranted, particularly characteristic can identified by proactive eye examination disc-at-risk characteristics optical coherence tomography.

Language: Английский

Citations

1
Recent advances in incretin-based therapy for MASLD: from single to dual or triple incretin receptor agonists DOI
Giovanni Targher, Alessandro Mantovani, Christopher D. Byrne

et al.

Gut, Journal Year: 2024, Volume and Issue: unknown, P. gutjnl - 334023

Published: Nov. 26, 2024

Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed the treatment of type 2 diabetes mellitus obesity, they were one first drug classes to be examined individuals with MASLD/MASH. Successful phase randomised clinical trials these agents resulted progression 3 (principally testing long-term efficacy subcutaneous semaglutide). Over last few years, addition GLP-1RAs, newer glucose-dependent insulinotropic peptide and/or glucagon agonist functions tested, increasing evidence from histological improvements MASLD/MASH, as well benefits on MASLD-related extrahepatic complications. Based this background evidence, single, dual or triple incretin are becoming an attractive promising option MASLD MASH, particularly coexisting obesity mellitus. In narrative review, we examine rapidly expanding body supporting role incretin-based pharmacotherapies delaying reversing MASH progression. We also discuss biology incretins putative hepatoprotective mechanisms managing MASH.

Language: Английский

Citations

4
Semaglutide and the risk of adverse liver outcomes in patients with nonalcoholic fatty liver disease and type 2 diabetes: a multi-institutional cohort study DOI

Chia-Chih Kuo,

Min‐Hsiang Chuang, Chun‐Hsien Li

et al.

Hepatology International, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Language: Английский

Citations

4
Glucagon‐like peptide‐1 receptor agonists discontinuation is higher in individuals with overweight and obesity without type 2 diabetes DOI
Gregory J. Grosicki, J. Graham Thomas, Nikhil V. Dhurandhar

et al.

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

Citations

0
Unexpected cardiovascular risks of glucagon‐like peptide‐1 receptor agonist and aspirin co‐administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study DOI Creative Commons

Chia‐Ming Lin,

Jo‐Ching Chen,

Gideon Meyerowitz‐Katz

et al.

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Aims To examine the cardiovascular safety of combining glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) with aspirin in individuals obesity, both and without type 2 diabetes (T2D). Materials Methods This propensity score matched cohort study analysed data from 946 579 T2D, using TriNetX US Global dataset. Participants were categorized into four groups: those receiving GLP‐1 RA plus versus alone, for diabetic non‐diabetic individuals. Cardiovascular outcomes adverse events evaluated over 5 years Cox proportional hazards models. Results Individuals obesity treated RAs showed significantly higher risks various compared to on alone. In obese individuals, combination therapy increased hypertensive heart diseases (HR 1.40, 95% CI 1.15–1.60), ischaemic disease 2.39, 1.92–2.97) failure 1.97, 1.54–2.53). Similar patterns observed T2D. Atrial fibrillation cardiac arrhythmias increasing hazard ratios time. The also led more frequent events, including gastrointestinal bleeding. Conclusions was associated monotherapy. These findings suggest that there may be combined use these treatments highlight need further research this possible complication regard treatment.

Language: Английский

Citations

0
Betagenin ameliorates diabetes by inducing insulin secretion and β-cell proliferation DOI Creative Commons

Tomotaka Yokoo,

Kazuhisa Watanabe, Kaoruko Iida

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108202 - 108202

Published: Jan. 1, 2025

Recent success with the use of glucagon-like peptide-1 (GLP-1) receptor analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors for treatment patients diabetes has highlighted role intestine as an endocrine organ. Gut-derived hormones, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), ghrelin, have important roles in control energy metabolism food intake, are associated metabolic syndrome. In this study, we isolated identified a new intestine-derived hormone, betagenin, showed that it stimulates insulin secretion β-cell proliferation suppresses apoptosis. Adenovirus-mediated expression betagenin restored blood glucose concentrations hemoglobin A1c (HbA1c) levels mice streptozotocin (STZ)-induced to normal increased their mass. Transgenic overexpressing exhibited more than three-fold higher mass wild-type mass, whereas knockout was four-fold lower. A synthetic peptide representing sequence purified secreted enhanced human mouse pancreatic islets stimulated line MIN6 through extracellular signal-regulated kinase (ERK) 1/2-dependent signaling. The intravenous administration STZ β-cells vivo, intraperitoneal ameliorated These results indicate may reduce concentration induce regeneration diabetes.

Language: Английский

Citations

0