Tirzepatide for Obesity Treatment and Diabetes Prevention

New England Journal of Medicine, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 13, 2024

BackgroundObesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown provide substantial sustained reductions in body weight persons with obesity over a 72-week period. Here, we report 3-year safety outcomes its efficacy reducing delaying progression diabetes both prediabetes.MethodsWe performed phase 3, double-blind, randomized, controlled trial which 2539 participants obesity, whom 1032 also had prediabetes, were assigned 1:1:1:1 ratio receive at once-weekly dose 5 mg, 10 or 15 mg placebo. The current involved who received their placebo for total 176 weeks, followed by 17-week off-treatment three key secondary end points, I error, percent change from baseline week onset during 176-week 193-week periods.ResultsAt mean among −12.3% 5-mg dose, −18.7% 10-mg −19.7% 15-mg as compared −1.3% those (P<0.001 all comparisons placebo). Fewer diagnosis groups than group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 0.1; P<0.001). After 17 weeks off treatment placebo, 2.4% 13.7% (hazard 0.12; CI, 0.1 0.2; Other coronavirus 2019, most common adverse events gastrointestinal, mild moderate severity occurred primarily dose-escalation period first 20 trial. No new signals identified.ConclusionsThree years prediabetes resulted reduction markedly lower risk that (Funded Eli Lilly; ClinicalTrials.gov number, NCT04184622.)

Язык: Английский

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The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines

Expert Opinion on Investigational Drugs, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Март 1, 2025

Introduction GLP-1-based therapies have changed the treatment of overweight/obesity. Liraglutide 3.0 mg daily, first GLP-1 RA approved for overweight, induced a weight loss 6–8%, Semaglutide 2.4 once weekly improved to about 12–15%, while dual GIP/GLP-1 receptor agonist tirzepatide has 20% in obese people without diabetes.

Язык: Английский

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The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation

Metabolism, Год журнала: 2024, Номер unknown, С. 156057 - 156057

Опубликована: Окт. 1, 2024

Язык: Английский

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Mechanistic insights into GLP-1 receptor agonist-induced weight loss through ceRNA network analysis

Genomics, Год журнала: 2025, Номер 117(2), С. 110988 - 110988

Опубликована: Янв. 5, 2025

GLP-1 receptor agonists (GLP-1RA) have been extensively utilized in the management of body weight individuals with obesity. Circular RNA (circRNA), a class covalently closed molecules, has garnered increasing attention for its potential role pathogenesis However, specific mechanisms through which circRNA contributes to GLP-1RA-induced loss remains elusive. High-throughput sequencing analyzed epididymal adipose tissue from obese mice under high-fat, and GLP-1RA intervention (600 μg/kg/d). The functions differentially expressed (DE) genes were enriched analyzed. circRNA-miRNA-mRNA interaction network was constructed Cytoscape, KEGG pathway gene enrichment validated via western blotting. A total 644 DEcircRNAs, 186 DEmiRNAs, 3474 DEmRNAs identified. Based on ceRNA score calculations, diagrams constructed. Gene Ontology (GO) analysis revealed that DERNAs linked lipid fatty acid metabolism. DE within pairs metabolism pathways, especially PI3K-Akt AMPK signaling pathways. induced phosphorylation AKT AMPK, subsequently led reduction SREBP-1, ACC, FAS. might activate pathways combat obesity circRNAs.

Язык: Английский

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Conjugated polymer of Multi-arm-PEG and dimethylsiloxane (CPMD) for the effective transdermal delivery of deoxycholic acid for fat reduction

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 159405 - 159405

Опубликована: Янв. 1, 2025

Язык: Английский

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Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP‐1RA‐based weight‐loss therapies

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Abstract Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have emerged as key agents for weight management, based on their marked efficacy observed in randomized controlled trials. While still limited, real‐world studies GLP‐1RA use populations with obesity are increasingly available. This narrative review discusses contemporary evidence demonstrating the utilization, clinical and comparative effectiveness, adverse effects of currently approved GLP‐1RA‐based weight‐loss therapies, that is, liraglutide, semaglutide tirzepatide. The reduction practice overall tends to be lower than trials; however, outcomes approach those seen trials when focusing highly adherent patients. Real‐world demonstrate high discontinuation rates GLP‐1RAs (20%–50%) within first year, much doses evaluated Evidence from observational type 2 diabetes or suggests frequent gastrointestinal disturbances users, also trials, but no clear increase risks severe events like pancreatitis pancreatic cancer, thyroid disorders, depression self‐harm. Further is needed understand possible associations eye disease other rare outcomes. We provide 10 areas particular importance further research space, including improved understanding exact drivers early suboptimal dosing, stopping treatment, investigations cost‐effectiveness hard settings, not only cardio‐reno‐metabolic obesity‐induced diseases neuropsychiatric disease, musculoskeletal infections. Plain Language Summary Recent advancements medications sparked a lot interest. so‐called GLP‐1 agonist gained attention, because they shown very effective, leading significant loss patients participating GLP‐1RAs, semaglutide, tirzepatide, help manage by mimicking hormones control blood sugar appetite. However, how these perform real life can different settings which carefully selected treatment plans closely followed. literature looks at used effectiveness safety settings. In real‐life practice, often less effective trial conditions. usually don't follow medication strictly data shows many do stick participants might, loss. who achieve results similar A major issue stop using them year due side costs medications, especially if covered insurance. Common include nausea digestive problems, main reasons taking treatments. These manageable decrease over time, this reviews found strong cause users. Despite challenges, effectively consistently, show substantial benefits loss, most so newest likely prevent weight‐related health conditions cardiovascular beneficial scarce emphasizes need more why improve dosing. It calls long‐term therapies various outcomes, mental health, cardiometabolic diseases. Overall, while valuable tool requires careful consideration individual patient factors, such ability plans, effects, afford medications. will make treatments wider range people them.

Язык: Английский

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Therapeutic Advances in Obesity: How Real-World Evidence Impacts Affordability Beyond Standard of Care

Pragmatic and Observational Research, Год журнала: 2024, Номер Volume 15, С. 139 - 149

Опубликована: Авг. 1, 2024

Obesity is currently considered a global epidemic, with rising prevalence worldwide and rather pessimistic projections. Based on its close interconnection various co-morbidities, such as diabetes mellitus cardiovascular disease, obesity associated significant increases in morbidity mortality, while it also poses substantial economic burden for national healthcare systems. Apparently, the majority of individuals classified obese do not achieve adequate weight loss adoption healthy lifestyle intervention, including dietary modification physical activity. Fortunately, during last decade, progress pharmacotherapy has been observed, introduction agents that have gained approval from regulatory authorities, namely semaglutide, liraglutide tirzepatide, due to their impressive results body reduction, alongside beneficial, pleiotropic effects. The aim present review article discuss evidence retrieved real-world studies regarding efficacy those treatment, emphasis cost-effectiveness data, towards an effort tackle efficiently progression epidemic.

Язык: Английский

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Navigating obesity: A comprehensive review of epidemiology, pathophysiology, complications and management strategies

The Innovation Medicine, Год журнала: 2024, Номер 2(3), С. 100090 - 100090

Опубликована: Янв. 1, 2024

<p>Obesity, a growing global health crisis, is driven by complex interplay of genetic, biological, environmental, behavioral, socio-cultural, and economic factors. This comprehensive review encapsulates the epidemiology, pathophysiological mechanism, myriad complications it triggers, such as cardiovascular diseases (CVDs), cancer, neurological disorders, respiratory ailments, digestive diseases, mobility impairments, psychological stress. The etiology obesity multifaceted, involving genetic predispositions, environmental influences, behavioral tendencies, socio-economic elements. underpinnings encompass multifaceted aspects energy metabolism, including regulation appetite, glucose, lipid, amino acid metabolism. also addresses seemingly contradictory roles in various offering insights into these phenomena. management multi-pronged, lifestyle modifications, pharmacological interventions, metabolic surgeries. Lifestyle changes are foundational, but advancements molecular techniques, digital technology, wearable devices, artificial intelligence opening new avenues for personalized treatment early intervention. Pharmacological surgery effective should be judiciously tailored to individual patient needs. underscores importance approach management, aiming curb escalating trend enhance future interventions treatments. ultimate goal synthesize current evidence innovative strategies combat effectively.</p>

Язык: Английский

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Comparing Clinical Practice Habits among Obesity Medicine Physicians by Patient, Physician and Clinic Factors

Obesity Pillars, Год журнала: 2025, Номер 13, С. 100157 - 100157

Опубликована: Янв. 7, 2025

While clinical practice habits vary by patient, physician and clinic factors in primary care, limited research has examined whether differences exist obesity medicine. Our objective was to compare such among medicine physicians certified the American Board of Obesity Medicine (ABOM). We conducted secondary analyses cross-sectional data from 2023 ABOM Practice Analysis Validation Survey. included three - prescribing anti-obesity medications (AOMs), off-label for weight reduction, hours (4-20 h/week versus >20 h/week). patient (patient population), (primary medical specialty, years experience) (practice setting, geographic catchment, accepts insurance care). bivariate using Χ2 tests. Among 565 ABOM-certified physicians, 71.5 % had specialties within care 9.2 predominantly treated children/adolescents with obesity. Overall, 97.5 prescribed AOMs 85.1 reduction. Fewer who compared no or treatment children (88.5 98.4 98.5 %, respectively; p < 0.001). 41.4 reported practicing h/week, which more likely occur as experience increased (i.e., 21.9 ​% 1-2 58.5 10+ years; ​< ​0.001). No significant occurred accepting insurance. findings may suggest that have consistent medication practices regardless factors, be particularly important patients seeking pharmacologic treatment. Most treat prescribe medications. These current rates are relatively higher than prior pediatric might help support access patients.

Язык: Английский

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Solving the Mystery of the Obesity Paradox: A Call for Better Data?

Critical Care Medicine, Год журнала: 2025, Номер 53(3), С. e730 - e732

Опубликована: Янв. 8, 2025

Rush University Medical Center, Chicago, IL. Dr. Siparsky received funding from Wolters Kluwer (UpToDate).

Язык: Английский

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