Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity

Diabetes Care, Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits GLP-1RA in select patient populations. In ongoing trials investigators are interrogating efficacy these agents new indications, including metabolic liver disease, peripheral artery Parkinson Alzheimer disease. success GLP-1–based medicines has spurred molecular entities combinations with unique pharmacokinetic pharmacodynamic profiles, exemplified tirzepatide, a GIP-GLP-1 coagonist. Simultaneously, investigational molecules such as maritide block GIP activate GLP-1 receptor, whereas retatrutide survodutide enable simultaneous activation glucagon receptors. Here I highlight evidence medicines, while discussing that inform safety, focusing on muscle strength, bone density fractures, exercise capacity, gastrointestinal motility, retained gastric contents anesthesia, pancreatic biliary tract disorders, risk cancer. Rapid progress highly efficacious anticipated differentiation newer subsets will provide greater opportunities use personalized medicine approaches to improve health people living cardiometabolic disorders.

Language: Английский

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A systematic review of the effect of semaglutide on lean mass: insights from clinical trials

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(5), P. 611 - 619

Published: March 23, 2024

Introduction Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood. This review investigates the effect of semaglutide in context obesity management.

Language: Английский

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Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Nutrients, Journal Year: 2023, Volume and Issue: 16(1), P. 63 - 63

Published: Dec. 25, 2023

Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) associated with faster more relevant impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk falls, frailty, overall quality life, mortality. PubMed/Medline, Scopus, Web Science, Google Scholar were searched for research articles, scientific reports, observational studies, trials, narrative systematic reviews, meta-analyses review evidence pathophysiology di-abetes-induced sarcopenia, its relevance in terms glucose control diabetes-related outcomes, diagnostic therapeutic challenges. The comprehensively addresses key elements definition criteria pathophysiological correlation be-tween T2D, related a critical role antihyperglycemic treatment health, perspectives specific targeting myokine signaling pathways involved regulation metabolism trophism. Prompt diagnosis adequate management, including lifestyle inter-vention, diet programs, micronutrient supplementation, physical exercise, pharmaco-logical treatment, are needed prevent or delay T2D.

Language: Английский

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

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: April 29, 2024

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 prevalence obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide liraglutide, designed for mellitus treatment, have been explored drugs the treatment obesity. This minireview describes molecular mechanisms liraglutide different metabolic pathways, its mechanism action processes appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, lipid metabolism. Finally, several clinical trial outcomes are described to show safety efficacy these management.

Language: Английский

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Editorial: Metabolic disorders as risk factors for osteoarthritis and targeted therapies for this pathology

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

represents the most common cause of disability in older people [3]. It results from a combination risk factors, mechanical overload, and altered joint mechanics [4]. Common factors POA include aging, weight excess, muscle weakness, sedentary lifestyle, recurring or persisting injuries [5].POA is characterized by marked rearrangement articular cartilage, resulting focal erosion extending cartilage surface to subchondral bone, chondrocyte hypertrophy, apoptosis, overgrowth outside with formation osteophytes, ossification bone. These alterations are mirrored detrimental macroscopic changes, such as ligament degeneration, secondary synovitis, overall rearrangement, prompting relevant deformities [6]. Given that tissue has scarce regenerative property [7], damage an irreversible derangement ranging minimal stable disease severe progressively deforming OA [8].Epidemiological evidence indicates frequent, its clinical presentation anticipated patients obesity, diabetes mellitus, metabolic syndrome [9]. Besides one but not only associated POA, recent investigation highlighted other influential mechanisms diseases, including hyperglycemia related pathways, insulin resistance, chronic low-grade inflammation adipose tissue, oxidative stress, lipid metabolism [10,11]. Therefore, treatments aiming control glucose levels, improve sensitivity, reduce body weight, ameliorate composition, systemic [12,13,14] may have therapeutic rationale preliminary studies suggest [15,16].The present research topic focused on role disorders pathogenesis knowledge pathophysiology, diagnostic biomarkers, novel OA.A comprehensive mechanistic review Adam et al. described putative illustrating relationship between dysmetabolism activity chondrocytes. First, accumulation chondrocytes affects interfering mitochondrial oxidation energetic substrates that, turn, metabolically processed via anaerobic glycolysis consequent energy loss increased production radical oxygen species. Second, both conditions foster impairment cellular function, necrosis apoptosis activating synovial inflammation. Mitochondrial dysfunction, observed experimental hyperglycemia, also diminished synthesis type 2 collagen coupled enhanced proteolysis proteoglycans neutrophil-derived metalloprotease [17].The pilot cross-sectional study assessing levels found established diagnosis diabetes, compared euglycemic individuals, had more signs synovitis expressed erythrocyte extravasation higher number mast cells macrophages. At same time, author less microvascular representation tissues those without positive magnitude severity knee pain [18].Overall, these indicate impaired control, dysmetabolic dysfunction pathophysiological maintaining exacerbating POA. Strategies expected outcomes.The Mendelian randomization analysis demonstrate causal serum ferritin European population, indicating specific genetic background iron predisposing factor [19]. The this fallout fields policy prevention primary care, simple laboratory exam can identify at-risk sketch them out for proper pharmacological non-pharmacological management.A National Health Nutrition Examination Survey roundness index, sensitive anthropometric value than mass index estimating amount visceral [26], positively correlated [20]. substantially line current suggesting particularly (well index) Tian X. colleagues provide update efficacy safety mesenchymal stem cells, placebo (saline), hyaluronic acid, glucocorticoids, platelet-rich plasma, non-surgical approaches, treatment [21]. systematic meta-analysis provided intraarticular administration administered at variable doses (single vs. double injections, 1 100 million per injection), improved several domains pain, inflammation, function. promising so far obtained, needed elucidate better efficacy, effectiveness, therapy There real need precise protocols time dose (dose-finding), well designs analyze long-term outcomes POA.Halabitska suggested potential link pancreatitis complication, based findings observational [22]. Their revealed exacerbates progression evidenced assessments using Western Ontario McMaster Universities (osteo)Arthritis (WOMAC) C-reactive protein. Moreover, nutritional status negatively. However, due relatively small sample size study, require validation through larger-scale research.To conclude, elucidates existence groups high developing involved relationship, some tools characterize adequate management. highlights basic research, especially considering interventions modern agents improving reducing weight.

Language: Английский

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Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1493 - 1493

Published: Jan. 25, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims investigate the molecular mechanisms underlying effectiveness of semaglutide on terms progression from steatosis fibrosis. We characterized exosomes ten patients (T2D) before (T0) after 12 months (T12) treatment once-weekly subcutaneous semaglutide. Six were considered responders therapy (R) based severity downgrading by at least one class according a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) stellate (LX-2) cells challenged R NR patients, isolated therapy. Exosomes both T0 significantly affected LX-2 viability. After treatment, only those restored cell viability, whereas did not. No effects observed HEPA-RG cells. T12 but not decreased production α-SMA, marker activation, model, ph-SMAD2 CTGF, involved fibrosis processes. TGF-β1 was modulated patients. As downstream effect, Vimentin, Collagen 1A1, Fibronectin extracellular matrix components also downregulated, measured droplets digital PCR. In conclusion, these results shed light potential improving MASLD.

Language: Английский

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Impact of Selected Glucagon-like Peptide-1 Receptor Agonists on Serum Lipids, Adipose Tissue, and Muscle Metabolism—A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8214 - 8214

Published: July 27, 2024

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are novel antihyperglycemic agents. By acting through the central nervous system, they increase satiety and reduce food intake, thus lowering body weight. Furthermore, secretion of insulin while decreasing production glucagon. However, recent studies suggest a more complex metabolic impact interaction with various other tissues. In our present review, we aim to provide summary effects GLP-1 RA on serum lipids, adipose tissue, muscle metabolism. It has been found that therapy is associated decreased cholesterol levels. Epicardial tissue thickness, hepatic lipid droplets, visceral fat volume were reduced in obese patients cardiovascular disease. level proinflammatory adipokines expression inflammatory genes. They have endoplasmic reticulum stress adipocytes, leading better adipocyte function increased microvascular blood flow resulting myocyte inhibited atrophy mass function. was also observed levels muscle-derived cytokines decreased, sensitivity increased, improved some clinical trials conducted very small number patients, which limits strength these observations.

Language: Английский

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Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: April 8, 2024

Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people all ages. In the last 40 years, incidence overweight and obesity almost tripled worldwide. The accumulation “visceral” tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure overt arterial hypertension, insulin-resistance type 2 diabetes mellitus (T2DM), dyslipidemia, kidney (CKD), obstructive sleep apnea. increasing use innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) sodium-glucose cotransporter-2 inhibitors (SGLT2-i), changing management its related cardiovascular complications significantly. These first considered only for T2DM treatment, are now used in patients visceral adiposity or obese patients, as no longer just risk factor but critical condition at basis common metabolic, cardiovascular, renal diseases. An adipocentric vision approach should become cornerstone integrated reducing avoiding onset obesity-related multiple factors their clinical complications. According recent progress basic research on adiposity, this narrative review aims contribute novel focusing pathophysiological therapeutic insights.

Language: Английский

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Oral Semaglutide in Routine Clinical Practice: Characteristics of People with Type 2 Diabetes Started on the Drug and Changes in Their Clinical Parameters after 24 Weeks of Treatment

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(11), P. 3054 - 3054

Published: May 23, 2024

Background/Objectives: Semaglutide is the unique once-daily oral glucagon-like receptor agonist presently available. Aims of this study were to describe clinical characteristics patients with type 2 diabetes (T2D) initiating semaglutide, assess its effects on glycemic control, body weight (BW) and tolerability in routine practice. Methods: Electronic medical records from two Italian clinics evaluated. Mean glycated hemoglobin (HbA1c) BW assessed adults T2D before 6 months after semaglutide prescription. Treatment discontinuation safety data reported. Results: A total 192 (44% female) presented a mean age 66 years, duration 10 HbA1c 7.9% 82.6 kg. Almost 50% obese. changes baseline follow up −0.7% −2.6 kg, respectively. Greater reduction was observed ≥ 8% <5 years. The composite endpoint ≤7% loss ≥5% achieved 22.5% participants. 40 (20.8%) discontinued treatment: 26 because gastrointestinal adverse events, due limited effectiveness lowering and/or BW. Conclusions: In real setting, showed suboptimal metabolic short obesity; significant improvement mainly more recent diagnosis, supporting use early phase disease.

Language: Английский

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Efficacy and safety of oral semaglutide in type 2 diabetes: A systematic review of real-world evidence

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2024, Volume and Issue: 18(5), P. 103024 - 103024

Published: May 1, 2024

Language: Английский

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