Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)
Published: Jan. 29, 2025
Language: Английский
Metabolism, Journal Year: 2024, Volume and Issue: 157, P. 155937 - 155937
Published: May 21, 2024
Metabolic dysfunction-associated steatotic liver disease (MASLD) closely associates with obesity and type 2 diabetes. Lifestyle intervention bariatric surgery aiming at substantial weight loss are cornerstones of MASLD treatment by improving histological outcomes reducing risks comorbidities. Originally developed as antihyperglycemic drugs, incretin (co-)agonists SGLT2 inhibitors also reduce steatosis cardiorenovascular events. Certain agonists effectively improve features MASLD, but not fibrosis. Of note, beneficial effects on may necessarily require loss. Despite moderate gain, one PPARγ agonist improved adipose tissue certain benefit fibrosis in post-hoc analyses. Likewise, the first THRβ-agonist was recently provisionally approved because significant improvements We here discuss liver-related metabolic induced different treatments their association Therefore, we compare results from clinical trials drugs acting via (incretin (co)agonists, inhibitors) those exerting no (pioglitazone; resmetirom). Furthermore, other development directly targeting hepatic lipid metabolism (lipogenesis inhibitors, FGF21 analogs) addressed. Although THRβ-agonism outcomes, concepts should consider all cardiometabolic risk factors for effective reduction morbidity mortality affected people.
Language: Английский
Citations
35
Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(7), P. 433 - 446
Published: April 3, 2024
Language: Английский
Citations
32
EClinicalMedicine, Journal Year: 2024, Volume and Issue: 75, P. 102782 - 102782
Published: Aug. 30, 2024
Language: Английский
Citations
29
Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(5), P. 301 - 318
Published: Feb. 7, 2024
Language: Английский
Citations
27
Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(7), P. 1534 - 1549.e7
Published: June 14, 2024
Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist, has, in clinical trials, demonstrated greater reductions glucose, body weight, and triglyceride levels compared with selective GLP-1R agonists people type 2 diabetes (T2D). However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte mouse models, we investigated how long-acting regulate fasted fed functions. In functional assays, enhanced insulin signaling, augmented glucose uptake, increased the conversion of glycerol cooperative manner insulin; however, absence insulin, lipolysis. diet-induced obese mice treated circulating were reduced during oral lipid challenge, lipoprotein-derived fatty acid uptake into adipose tissue was increased. Our findings support model for modulate both function differentially cooperating augment clearance state while enhancing release when are state.
Language: Английский
Citations
27
Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3829 - 3853
Published: July 1, 2024
Language: Английский
Citations
24
Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 24, 2024
Abstract INTRODUCTION Emerging preclinical evidence suggests that semaglutide, a glucagon‐like peptide receptor agonist (GLP‐1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration neuroinflammation. However, real‐world its ability to protect Alzheimer's disease (AD) is lacking. METHODS We conducted emulation target trials based on nationwide database of electronic health records (EHRs) 116 million US patients. Seven were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide seven other antidiabetic medications. First‐ever occurred within 3‐year follow‐up period was examined using Cox proportional hazards Kaplan–Meier survival analyses. RESULTS Semaglutide associated significantly reduced risk first‐time diagnosis, most strongly compared insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 0.51]) weakly GLP‐1RAs (HR, 0.59 0.37 0.95]). Similar results seen across obesity status, gender, age groups. DISCUSSION These findings support further studies assess semaglutide's potential in preventing AD. HIGHLIGHTS 40% 70% risks medications, including GLP‐1RAs. lower AD‐related medication prescriptions. reductions Our provide supporting the clinical benefits mitigating initiation development T2DM. delaying or
Language: Английский
Citations
19
Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 24, 2024
Language: Английский
Citations
19
Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 59(4), P. 475 - 491
Published: Jan. 2, 2024
Summary Background Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently bariatric therapies, there are significant pharmacological advancements. Aims To conduct a narrative review neurohormonal physiological understanding weight gain obesity, development, clinical testing, indications, expected outcomes, associated risks current FDA‐approved upcoming anti‐obesity medications (AOMs). Methods We conducted comprehensive in PubMed for articles on pathophysiology complications including terms ‘neurohormonal’, ‘obesity’, ‘incretin’, ‘weight loss’. Next, we searched trial data all AOMs, both generic trade names orlistat, phentermine/topiramate, bupropion/naltrexone, liraglutide, semaglutide. Additional searches were tirzepatide retatrutide ‐ expecting regulatory approval. Searches included combinations related to mechanism action, side effects, risks, future directions. Results reviewed specific role incretins glucagon. Clinical supporting use various loss presented, placebo‐controlled or, when available, head‐to‐head trials. Beneficial metabolic impact liver disease, adverse effects discussed, altered gastrointestinal motility risk periprocedural aspiration. Conclusion AOMs have established efficacy effectiveness even beyond 52 weeks. Further options, such as dual triple incretins, probable forthcoming additions practice combating obesity its consequences dysfunction‐associated steatotic disease.
Language: Английский
Citations
18
AJP Heart and Circulatory Physiology, Journal Year: 2024, Volume and Issue: 326(5), P. H1159 - H1176
Published: March 1, 2024
Atherosclerotic cardiovascular disease is a chronic condition that often copresents with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetics endorsed by major professional societies for improving glycemic status reducing atherosclerotic risk in people living diabetes. Although the cardioprotective efficacy of GLP-1RAs their relationship traditional factors well established, there paucity publications have summarized potentially direct mechanisms through which mitigate atherosclerosis. This review aims to narrow this gap providing comprehensive in-depth mechanistic insight into antiatherosclerotic properties demonstrated across large outcome trials. Herein, we describe landmark trials triggered widespread excitement around as modern class agents, followed summary origins action. The effects at each pathophysiological milestone atherosclerosis, observed clinical trials, animal models, cell culture studies, described detail. Specifically, provides recent preclinical evidence suggest preserve vessel health part preventing endothelial dysfunction, achieved primarily promotion angiogenesis inhibition oxidative stress. These protective addition broad range processes target downstream include systemic inflammation, monocyte recruitment, proinflammatory macrophage foam formation, vascular smooth muscle proliferation, plaque development.
Language: Английский
Citations
16