Managing cardiovascular events, hyperglycemia, and obesity in type 2 diabetes through microRNA regulation linked to glucagon-like peptide-1 receptor agonists

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 10, 2025

Type 2 diabetes mellitus (T2DM) is usually complicated by cardiovascular diseases, hyperglycemia, and obesity, which worsen the outcome for patient. Since recent evidence underlines epigenetic role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in management these comorbidities, this study compared effects agents, namely liraglutide, semaglutide, dulaglutide, exenatide, on miRNA regulation T2DM. GLP-1RAs modify expression miRNAs involved endothelial function, sugar metabolism, adipogenesis, including but not limited to miR-27b, miR-130a, miR-210. Baseline miR-15a-5p predict weight loss, while higher miR-378-3p miR-126-3p levels are related better glycemic control lower HbA1c FPG at one year post-treatment. miR-375-5p was also reported as a predictor levels. Liraglutide has protecting effect against pancreatic β-cell apoptosis downregulating miR-139-5p. The highly-expressed miR-375 islets can be considered biomarker assessing cytoprotective action β-cells. enhance responsiveness promoting GLP-1 through suppression miR-204. While dulaglutide reduce both systolic diastolic blood pressures, lixisenatide exenatide QW did reveal such an effect. long-acting exenatide-induced miR-29b-3p required protection diabetic cardiomyopathy. modulates critical regulators cell function atherosclerosis, miR-93-5p, miR-26a-5p, miR-181a-5p. Eventually, exosomal miRNAs, miR-192, implicated development fibrosis inflammation T2DM micro-cardiovascular outcomes like DKD DR. Additional studies will needed elucidation relations between GLP-1RA-induced clinical-laboratory findings concerning diverse populations, gender, presence other comorbid states treated patients with

Language: Английский

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The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists in the Management of Obesity-Related Heart Failure with Preserved Ejection Fraction: Benefits beyond What Scales Can Measure?

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 2112 - 2112

Published: Sept. 16, 2024

Obesity is a significant predisposing factor for heart failure with preserved ejection fraction (HFpEF). Although substantial proportion of individuals HFpEF also have obesity, those obesity are under-represented in clinical trials failure. In turn, current guidelines provided limited recommendations the medical management this patient population. Both and diabetes induce pro-inflammatory state that can contribute to endothelial dysfunction coronary microvascular impairment, finally resulting HFpEF. Additionally, leads increased epicardial chest wall adiposity, which enhances ventricular interdependence. This condition further aggravated by plasma blood volume expansion excessive vasoconstriction, ultimately worsening Despite well-documented benefits GLP-1 receptor agonists subjects diabetes, or both, their role obesity-related remains unclear. light recently published literature, review aims investigate potential mechanisms synthesize available evidence regarding patients

Language: Английский

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GLP-1 receptor agonists in diabetes and weight loss: the double-edged sword of innovation and risks

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2025, Volume and Issue: 5

Published: Jan. 9, 2025

In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists have gained widespread popularity not only as effective agents in the management of type 2 diabetes but also for their beneficial impact on weight loss. Additionally, this surge interest has been underpinned by pleiotropic effects and spurred further investigation into potential applications beyond care. However, expanding adoption GLP-1 brings with it a set challenges complications. With promising therapeutic comes an increased scrutiny side effects.GLP-1 mimic action native peptide, enhancing insulin secretion, suppressing glucagon release, slowing gastric emptying, increasing satiety. Initially introduced to treat diabetes, they were found important effect loss; paradigm shift medical obesity may -in fact -be imminent, per opinion non-medical pundits [1][2][3]. Drugs like semaglutide, liraglutide or tirzepatide (a dual GIP analog) led significant reduction participants clinical trials real-world settings, making them popular patients physicians alike.The success lies multifaceted mechanisms, which address complex physiological pathways hunger, satiety, glucose metabolism. These drugs target pancreas gut brain's hypothalamic appetite-regulating centers. Some analogs be attributed actions central nervous system neurotransmitter secretion/action; enhance gamma-aminobutyric acid (GABA) activity, restore dopaminergic activity act parallel peptide YY (PYY) [4][5][6]. sense, are redefining approach metabolic disease addressing glycemic control influencing body cardiovascular health. Currently, long-term consequences analog use over 1.5 -2 years look promising; published meta-analyses, reduced morbidity mortality noted, whereas no appearance gastrointestinal neoplasia observed [7][8].The foster ongoing research new indications.Evidence suggests these benefits, studies indicating risk among people who [9][10][11][12]. explored GLP-1[3] liver health, including benefit treatment dysfunction associated fatty (MASLD) [13][14]. The anti-inflammatory neuroprotective properties being investigated, implications neurodegenerative conditions Alzheimer's [15][16][17]. Such raises possibility broader agonists, influence extends traditional management.As exciting advancements are, raise critical questions about society's preference pharmacological solutions lifestyle interventions diet exercise. mindset many practitioners, allure weight-loss medications indeed outweigh need changes, despite evidence that physical fundamental components sustainable Surveys internet worldwide indicated frank increase searches [18][19]. revealed more interested pharmaceutical loss than modifications. This trend is fueled relative ease accessibility medications, coupled perception can yield rapid, visible results (traditional social media statements "celebrities" add trend).Pharmaceutical companies responded demand pipeline drugs, based mechanisms agonists. focus pharmacotherapy, however, risks overshadowing essential role nonpharmacological chronic prevention management. It healthcare providers emphasize while play valuable plans, substitutes balanced diet, regular other modifications.While largely considered safe, usage drawn attention rare adverse events. Nonarteritic anterior ischemic optic neuropathy (NAION), idiopathic injury nerve head, marked sudden, painless vision eye swelling disc, reported association agonists' use, though such cases remain [20]. might trigger NAION yet fully understood, necessary determine whether causal [4] relationship exists. practice, experiencing visual disturbances therapy should evaluated promptly, consideration given discontinuing medication if link suspected.Pancreatitis known Although absolute low, pancreatitis severe even life-threatening. receptors expressed pancreas, researchers hypothesize pancreatic function ways could predispose certain individuals inflammation. Studies yielded mixed negative [21-23], there definitive linking higher incidence pancreatitis, remains listed effect.Other events, possibly linked analogs, include muscle mass loss, dermatological/hypersensitivity reactions, heart rate, left ventricular ejection fraction depressionThe emergence safety concerns reinforces importance individualized patient assessment before prescribing particularly those history disorders factors. Healthcare must engage thorough discussions patients, weighing benefits against ensuring understand signs symptoms events.The advent represents milestone obesity, presents challenge balancing drive innovation safety. landscape, devoid risks, detract from comprehensive, While offer much promise, underscore reality pharmacotherapy alone cannot root causes diseases. As we move forward, will crucial develop nuanced prescription drugs. Educating modification, well essential. needed clarify underlying events identify at [27].[5] transformed landscape management, offering extend control.However, reliance reflects societal de-emphasizing exercise managing although rare, serves reminder complexities drug careful selection monitoring. our pursuit advancements, innovative pharmacotherapies commitment safe responsible practice. providers, responsibility embrace tools modern medicine provides vigilant safeguarding health through informed, evidence-based promise undeniable, so caution judicious quest improve outcomes.

Language: Английский

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Obesity: Recent Advances and Future Perspectives

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 368 - 368

Published: Feb. 5, 2025

As reported in the World Obesity Atlas 2024 by Federation, projections for 2035 suggest that more than 1 [...]

Language: Английский

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Mitigating Increased Cardiovascular Risk in Patients with Obstructive Sleep Apnea Using GLP-1 Receptor Agonists and SGLT2 Inhibitors: Hype or Hope?

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2503 - 2503

Published: Nov. 1, 2024

Obstructive sleep apnea (OSA) is a prevalent condition associated with increased cardiovascular risk, particularly in individuals comorbid obesity and type 2 diabetes (T2D). Despite the widespread use of continuous positive airway pressure (CPAP) for OSA management, adherence remains suboptimal, CPAP has not consistently demonstrated reductions surrogate events. Recently, attention focused on glucagon-like peptide-1 receptor agonists (GLP-1RAs) sodium-glucose cotransporter-2 (SGLT2) inhibitors as potential therapeutic agents mitigating risk patients. These agents, originally developed T2D have pleiotropic effects, including significant weight loss, blood reduction, amelioration endothelial dysfunction arterial stiffness, along anti-inflammatory benefits, which may be beneficial OSA. Emerging clinical evidence suggests that GLP-1RAs SGLT2 can reduce severity improve daytime sleepiness, potentially reversing adverse effects observed This review explores pathophysiological mechanisms linking disease evaluates roles addressing Further research, long-term trials, necessary to establish effectiveness these therapies reducing events improving patients' reported outcomes this population.

Language: Английский

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Integrating social determinants of health into global approaches to early-onset type 2 diabetes

Journal of Diabetes and its Complications, Journal Year: 2025, Volume and Issue: 39(4), P. 108982 - 108982

Published: March 5, 2025

Language: Английский

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Adherence to statins and development of atherosclerosis-related events. A systematic review and meta-analysis

Journal of Diabetes and its Complications, Journal Year: 2025, Volume and Issue: unknown, P. 109040 - 109040

Published: April 1, 2025

Language: Английский

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Pharmacokinetics and Safety of a Fixed‐Dose Combination of Alogliptin and Extended‐Release Metformin Under Fasting and/or Fed Conditions in Healthy Adults

Clinical Pharmacology in Drug Development, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract This phase 1, randomized, open‐label, 2 × crossover study evaluated the bioequivalence of fixed‐dose combination (FDC) formulations alogliptin (ALO) and metformin extended‐release (MET XR) compared to their individual assessed effect food on FDC pharmacokinetics in healthy participants. The comprised high‐dose (ALO 25 mg/MET XR 1000 mg) low‐dose 12.5 500 mg), both conducted under fasting conditions, fed conditions. Among enrolled participants, 46 50 completed study, 45 51 22 26 study. Plasma concentrations were analyzed using liquid chromatography‐tandem mass spectrometry. geometric mean ratios AUC last C max for versus within range (0.80‐1.25) ALO MET XR. ALO's unaffected by food, while exhibited a significant effect, with increasing factor 1.63 T delayed hours. Given these findings, should be administered consistent monotherapy recommendations.

Language: Английский

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GLP-1 receptor agonists and MASLD in diabetes: A promising path?

Journal of Diabetes and its Complications, Journal Year: 2025, Volume and Issue: unknown, P. 109041 - 109041

Published: April 1, 2025

Language: Английский

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Novel antidiabetic therapies in patients with peripheral artery disease: current perspective

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2024, Volume and Issue: 5

Published: Nov. 26, 2024

1 IntroductionPeripheral artery disease (PAD) is the third leading cause of atherosclerosis-related morbidity, after coronary and cerebrovascular diseases. Approximations its prevalence are 10–26% in general adult population increase with age. PAD bears burden functional decline major adverse limb events (MALE), consisting chronic limb-threatening ischemia, acute amputations. Chronic ischemia associated 20% mortality amputations one year. The lifetime risk varies based on traditional factors, including diabetes, smoking, dyslipidaemia, hypertension, a sedentary lifestyle. inflammation, metals, air pollution, depression also seem to play role. Furthermore, albuminuria related leg retinopathy PAD, regardless duration diabetes haemoglobin A1c (HbA1c) levels (1). has an increased propensity not only for MALE, but significant cardiovascular (MACE). Coronary prevalent 30–50% patients while presence polyvascular further increases susceptibility MACE (2).Diabetes significantly affecting 20–28% people diabetes. crucial factor diabetic foot ulcers, 50% those ulcers have PAD. diagnosis ischaemia challenging due atypical symptoms, particularly absence intermittent claudication rest pain attributed peripheral neuropathy, medial calcification that affects precision non-invasive diagnostic tests. In progression differs from individuals without manifesting itself more distal arteries, multiple bilateral arterial segments, reducing collateral growth, thus increasing amputation. leads worse outcomes, non-healing gangrene, amputation, disease. Approximately 70% non-traumatic lower extremity United States can be this disproportional overall 12% (2, 3). Post-amputation severe, dying 5 years, comparable many cancers (4).As MALE MACE, comprehensive multidisciplinary management highest importance, comprising non-pharmacologic intervention (lifestyle modification: smoking cessation, supervised exercise therapy, Mediterranean diet, weight loss), pharmacologic (antihypertensive lipid lowering antithrombotic glucose therapy) invasive therapy (endovascular surgical revascularization) 5). Revascularization procedures performed improve local conditions; however, who undergone these still face higher compared their counterparts such (2). 2 New antidiabetic therapies diseaseNew consist mainly sodium-glucose cotransporter-2 inhibitors (SGLT2i) glucagon-like peptide 1-receptor agonists (GLP1-RA). Representatives drug classes been reduction type (6). However, main outcome trials, most enrolled had concomitant disease, were underrepresented Even though, proven risk, which goes beyond mere glycaemic control, drugs both benefit recommended by 2023 ESC Guidelines treatment 2024 aortic diseases as choice reduce independent baseline or target HbA1c (5, 7). SGLT2i effectively kidney heart failure patients, common comorbidities seen yet meta-analysis 20 trials did find impact incidence contrast, US databases linked 1.65-fold GLP-1RA. A similar signal was observed 1.97-fold canagliflozin. It should emphasized amputation canagliflozin CANVAS trial, confirmed CREDENCE trial. post hoc analysis trial revealed majority minor infection, dose Instead, primarily previous established factors despite specific identified etiological mechanism. anticipated number less than averted (8). Additionally, conducted Lin et al. showed treated exhibited modest use SGLT2i. This greater loss cohort, addition diastolic pressure pronounced reductions systolic blood pressures, all potential markers volume depletion (9). Thus, underlying mechanism contributes elevated diuretic-induced hypovolemia, provoked SGLT2i, resulting reduced perfusion extremities. hypoperfusion initiate tissue necrosis, subsequently diuretic effect question likely during initial phase (10). mentioned probably specifical (canagliflozin) class effect, there no other obvious (11). International Working Group Diabetic Foot advises against starting any drug-naïve gangrene suggests stopping until healing occurs, carefully balancing individual risk-benefit ratio (3). GLP-1RA within two years following commencement, decreased (12). finding aligns various putative anti-atherosclerotic mechanisms, enhancement systemic microcirculation, inflammation oxidative stress, well improvements endothelial function vasodilation (13). Some expected shed additionally (14). recent LEADER SUSTAIN-6 liraglutide semaglutide demonstrated consistent efficacy Consequently, it appears show evident superiority medications respect PAD-related (15). could emerge even obesity since SELECT 2,4 mg. included 8.6% (16). terms current emerging therapies, great anticipation SOUL event-driven, double-blind, placebo-controlled evaluated first oral GLP1-RA, (14 mg once daily) placebo, atherosclerotic and/or Among individuals, 15.7% symptomatic category mutually exclusive territories (17). Recent announcement 14% (18). tirzepatide, dual GIP/GLP-1 receptor agonist, being SURPASS-CVOT designed randomized, active-controlled outcomes People (25.3% PAD) subjected weekly subcutaneous injection tirzepatide up 15 1.5 dulaglutide. noninferiority time dulaglutide will confirm safety tirzepatied placebo determine whether produces active comparator (demonstrating superiority) (19). And analysing mostly indirect data, STARDUST daily 1.8 6 months directly detected transcutaneous oxygen (TcPO2) confirming prevention clinical (20). results STRIDE eagerly 52-week week would maximum walking distance constant load treadmill median pain-free 114 m (maximum 186 m). Secondary include quality life cardiometabolic parameters (21). ongoing objective evaluating (NCT04146155) 24 weeks distance.3 DiscussionThe field sufficiently explored demonstrate possible favourable benefits new therapies. Although shown definitive data come, effects validated. On contrary, wide range conditions populations exists lack direct evaluate effectiveness With certain negative indicators, may never occur, casting pessimistic outlook demographic patients. advent personalized medicine underscores importance tailoring approaches each patient. Therefore, imperative meticulously assess balance risks ensure beneficial does exclude patient much gain use.

Language: Английский

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