Metabolism, Journal Year: 2024, Volume and Issue: unknown, P. 156057 - 156057
Published: Oct. 1, 2024
Language: Английский
New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(13), P. 1193 - 1205
Published: June 21, 2024
BackgroundObstructive sleep apnea is characterized by disordered breathing during and associated with major cardiovascular complications; excess adiposity an etiologic risk factor. Tirzepatide may be a potential treatment.MethodsWe conducted two phase 3, double-blind, randomized, controlled trials involving adults moderate-to-severe obstructive obesity. Participants who were not receiving treatment positive airway pressure (PAP) at baseline enrolled in trial 1, those PAP therapy 2. The participants assigned 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) placebo for 52 weeks. primary end point was change apnea–hypopnea index (AHI, number apneas hypopneas hour sleep) from baseline. Key multiplicity-controlled secondary points included percent AHI body weight changes hypoxic burden, patient-reported impairment disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, systolic blood pressure.ResultsAt baseline, mean 51.5 events per 1 49.5 2, body-mass (BMI, kilograms divided square height meters) 39.1 38.7, respectively. In week −25.3 (95% confidence interval [CI], −29.3 −21.2) −5.3 CI, −9.4 −1.1) placebo, estimated difference −20.0 −25.8 −14.2) (P<0.001). −33.2 −25.4) −5.5 −9.9 −1.2) −23.8 −29.6 −17.9) Significant improvements measurements all prespecified key observed as compared placebo. most frequently reported adverse gastrointestinal nature mostly mild moderate severity.ConclusionsAmong persons obesity, reduced AHI, weight, hsCRP improved sleep-related outcomes. (Funded Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.)
Language: Английский
Citations
147
International Journal of Obesity, Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 1, 2024
Abstract Obesity is a chronic disease associated with increased risk of obesity-related complications and mortality. Our better understanding the weight regulation mechanisms role gut-brain axis on appetite has led to development safe effective entero-pancreatic hormone-based treatments for obesity such as glucagon-like peptide-1 (GLP-1) receptor agonists (RA). Semaglutide 2.4 mg once weekly, subcutaneously administered GLP-1 RA approved treatment in 2021, results 15–17% mean loss (WL) evidence cardioprotection. Oral are also under early data shows similar WL efficacy semaglutide mg. Looking next generation treatments, combinations other hormones complementary actions and/or synergistic potential (such glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin) investigation enhance cardiometabolic benefits RA. Tirzepatide, dual GLP-1/GIP agonist been glycaemic control type 2 diabetes well management leading up 22.5% phase 3 trials. Other including cagrisema (GLP-1/amylin RA) triple retatrutide (GLP-1/GIP/glucagon have progressed trials suggests that may lead even greater than tirzepatide. Additionally, agents different action (e.g. bimagrumab) improve body composition during clinical We new era pharmacotherapy where approach achieved bariatric surgery. In this review, we present safety pipeline pharmacotherapies focus consider implications challenges bring.
Language: Английский
Citations
112
JAMA, Journal Year: 2024, Volume and Issue: 332(7), P. 571 - 571
Published: Aug. 20, 2024
Obesity affects approximately 19% of women and 14% men worldwide is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite significantly improve outcomes, such as type 2 diabetes, hypertension, dyslipidemia.
Language: Английский
Citations
50
New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 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.)
Language: Английский
Citations
48
Nature, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 18, 2024
Abstract Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity 1,2 . However, maintaining loss considerable challenge, especially as the seems retain an obesogenic memory that defends against changes 3,4 Overcoming this barrier for long-term treatment success difficult because molecular mechanisms underpinning phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show both human mouse adipose tissues cellular transcriptional after appreciable loss. Furthermore, find persistent obesity-induced alterations epigenome of adipocytes negatively affect their function response stimuli. Mice carrying accelerated rebound gain, epigenetic can explain future deregulation further high-fat diet feeding. In summary, our findings indicate existence memory, on basis stable changes, probably other cell types. These seem prime cells pathological responses environment, contributing problematic ‘yo-yo’ effect often seen with dieting. Targeting these could management outcomes.
Language: Английский
Citations
39
Diabetes Care, Journal Year: 2024, Volume and Issue: 47(10), P. 1718 - 1730
Published: April 30, 2024
This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and importance resistance exercise preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight in randomized trials, effects that may be enhanced combination with glucose-dependent insulinotropic polypeptide (GIP) agonists. Liraglutide semaglutide (GLP-1RA), tirzepatide (GLP-1 GIP dual agonist), retatrutide (GLP-1, GIP, glucagon triple agonist) are peptides incretin agonist activity ∼15-24% adults overweight obesity, alongside beneficial impacts blood pressure, cholesterol, glucose, insulin. However, these agents also rapid significant mass (∼10% or ∼6 kg), comparable a decade more aging. Maintaining muscle function as humans age is crucial avoiding sarcopenia frailty, strongly linked morbidity mortality. Studies indicate supervised training interventions duration >10 weeks can elicit large increases (∼3 kg) strength (∼25%) men women. After low-calorie diet, combining aerobic liraglutide improved maintenance compared either alone. Retaining during therapy could blunt body (and fat) regain cessation pharmacotherapy. We propose tailored recommended an adjunct optimize changes composition by preserving while achieving fat loss.
Language: Английский
Citations
34
The Lancet, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Over the past several decades, overweight and obesity epidemic in USA has resulted a significant health economic burden. Understanding current trends future trajectories at both national state levels is crucial for assessing success of existing interventions informing policy changes. We estimated prevalence from 1990 to 2021 with forecasts 2050 children adolescents (aged 5-24 years) adults ≥25 level. Additionally, we derived state-specific estimates projections older 15-24 all 50 states Washington, DC.
Language: Английский
Citations
30
EClinicalMedicine, Journal Year: 2024, Volume and Issue: 75, P. 102782 - 102782
Published: Aug. 30, 2024
Language: Английский
Citations
29
JAMA, Journal Year: 2024, Volume and Issue: unknown
Published: May 31, 2024
Obesity has become a global public health concern and China the largest number of affected people worldwide.
Language: Английский
Citations
27
Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3829 - 3853
Published: July 1, 2024
Language: Английский
Citations
24