Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

The Lancet, Journal Year: 2023, Volume and Issue: 402(10402), P. 613 - 626

Published: June 26, 2023

Language: Английский

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Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

JAMA, Journal Year: 2023, Volume and Issue: 331(1), P. 38 - 38

Published: Dec. 11, 2023

Importance The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective To assess the tirzepatide, diet and physical activity, maintenance reduction. Design, Setting, Participants This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries a 36-week, open-label lead-in period followed by 52-week, double-blind, placebo-controlled included adults body mass index greater than or equal to 30 27 weight-related complication, excluding diabetes. Interventions (n = 783) enrolled an received once-weekly subcutaneous maximum tolerated dose (10 15 mg) for 36 weeks. At week 36, total 670 participants were (1:1) continue receiving 335) switch placebo 52 Main Outcomes Measures primary end point was mean percent change from (randomization) 88. Key secondary points proportion 88 who maintained least 80% loss during period. Results 670; age, 48 years; 473 [71%] women; weight, 107.3 kg) completed 36-week experienced 20.9%. −5.5% vs 14.0% (difference, −19.4% [95% CI, −21.2% −17.7%]; P < .001). Overall, 300 (89.5%) weeks compared 16.6% ( overall 0 25.3% 9.9% placebo. most common adverse events mostly mild moderate gastrointestinal events, which occurred more commonly Conclusions Relevance In obesity overweight, withdrawing led substantial regain lost whereas augmented Trial Registration ClinicalTrials.gov Identifier: NCT04660643

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(7), P. 463 - 474

Published: March 28, 2023

Language: Английский

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Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(11), P. 2909 - 2918

Published: Oct. 15, 2023

Abstract The effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on weight reduction after successful intensive lifestyle intervention are unknown. This double-blind, placebo-controlled trial randomized (1:1) adults with body mass index ≥30 or ≥27 kg/m 2 at least one obesity-related complication (excluding diabetes), who achieved ≥5.0% 12-week intervention, to tirzepatide maximum tolerated dose (10 15 mg) placebo once weekly for 72 weeks ( n = 579). treatment regimen estimand assessed regardless adherence in the intention-to-treat population. coprimary endpoint additional mean per cent change from randomization week was met changes −18.4% (standard error (s.e.) 0.7) 2.5% (s.e. 1.0) (estimated difference −20.8 percentage points (95% confidence interval (CI) −23.2%, −18.5%; P < 0.001). participants achieving ≥5% 87.5% 2.2) 16.5% 3.0) this threshold (odds ratio 34.6%; 95% CI 19.2%, 62.6%; most common adverse events were gastrointestinal, being mild moderate severity. Tirzepatide provided substantial had intervention. ClinicalTrials.gov registration: NCT04657016 .

Language: Английский

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The expanding incretin universe: from basic biology to clinical translation

Diabetologia, Journal Year: 2023, Volume and Issue: 66(10), P. 1765 - 1779

Published: March 28, 2023

Language: Английский

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Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation

Cell Metabolism, Journal Year: 2023, Volume and Issue: 36(1), P. 130 - 143.e5

Published: Dec. 18, 2023

Language: Английский

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Inter-organ crosstalk during development and progression of type 2 diabetes mellitus

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 20(1), P. 27 - 49

Published: Oct. 16, 2023

Language: Английский

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The intestine as an endocrine organ and the role of gut hormones in metabolic regulation

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(12), P. 784 - 796

Published: Aug. 25, 2023

Language: Английский

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Changes in lean body mass with glucagon‐like peptide‐1‐based therapies and mitigation strategies

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(S4), P. 16 - 27

Published: June 27, 2024

Abstract Weight loss induced by glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and dual (GLP‐1R)/glucose‐dependent insulinotropic polypeptide is coming closer to the magnitudes achieved with surgery. However, greater weight there concern about potential side effects on muscle quantity (mass), health function. There heterogeneity in reported of GLP‐1‐based therapies lean mass changes clinical trials: some studies, reductions range between 40% 60% as a proportion total lost, while other studies show approximately 15% or less lost. are several reasons underlying this heterogeneity, including population, drug‐specific/molecular, comorbidity effects. Furthermore, may not always reflect former measure includes only but also organs, bone, fluids, water fat tissue. Based contemporary evidence addition magnetic resonance imaging‐based skeletal GLP‐1RA treatments appear be adaptive: volume seem commensurate what expected given ageing, disease status, achieved, improvement insulin sensitivity infiltration likely contributes an adaptive process improved quality, lowering probability for strength Nevertheless, factors such older age severity influence selection appropriate candidates these due risk sarcopenia. To further improve during loss, pharmacological maintain designed combination under development. Future research should focus more accurate meaningful assessments mass, composition, well function, mobility strength, better define their impact substantial number patients who will taking medications into future.

Language: Английский

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