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Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map.

BACKGROUND: Considering the global burden of diabetes and associated cardiovascular disease, an urgent need exists for the best treatment, w … lar events [0·91; 0·83-1·00]), liraglutide (major adverse cardiovascular events [0·86; 0·77-0·96]), semaglutide (major adverse cardiovascular events [0·76; 0·62-0·92] and stroke [0·67; 0·45-1·00]), sodium-glucose co-transporter-2 inhibitors as a class (major adverse cardiovascular events [0·87; 0·82-0·93], death from cardiovascular disease [0·82; 0·75-0·90], …

Medical therapy to treat obesity and optimize fertility in women of reproductive age: a narrative review.

BACKGROUND: Overweight and obesity-chronic illnesses in which an increase in body fat promotes adipose tissue dysfunction and abnormal fat m … tly 6 FDA-approved medications for weight loss: 2 GLP1-receptor agonists (GLP1-RAs) liraglutide and semaglutide, 1 dual GLP-1 and gastric inhibitory peptide agonist (GLP1-GIP) tirzepatide, Contrave (naltrexone/bupropion), Qsymia (phentermine/Topamax), and Xenical (orlistat). GLP1-RAs reduce food cravings, appetite, and "food noise" and improve insulin sensiti …

GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: a living benefit-harm modelling study.

BACKGROUND: The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains uncle … iduals with less concern about harm outcomes. The net benefit for a 10% weight loss was highest for semaglutide, followed by liraglutide and tirzepatide, with 2-year probabilities of 0.96, 0.72, and 0.60, respectively. INTERPRETATION: The benefit of GLP-1 RAs exceeded the harms for weight loss in the first 2 years of treatment, yet the net benefit was depend …

Exploring the top 30 drugs associated with drug-induced constipation based on the FDA adverse event reporting system.

ObjectiveThis project aims to identify the top 30 drugs most commonly associated with constipation and their signal values within the FDA Adverse Event Reporting System database.MethodsWe extracted adverse drug events (ADEs) related to constipation from the FAERS database spanning from January 1, 2004, to September 30, 2023. We compiled the 30 most frequently reported drugs based on the frequency of constipation events. We employed signal detection methodologies to ascertain whether these drugs elicited significant signals, including reporting odds ratio, proportional reporting ratio, multi-it

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… Thirteen drugs (sevelamer carbonate, pomalidomide, cabozantinib, patiromer, solifenacin succinate, orlistat, lenalidomide, dulaglutide, erenumab, nintedanib, niraparib, oxycodone, and semaglutide) exhibited percentages exceeding 2% in specific years. … Gastrointestinal adverse events associated with semaglutide: a pharmacovigilance study based on FDA adverse event reporting system. Front. Public Health 10, 996179. 10.3389/fpubh.2022.996179 Stojanovska V., Sakkal S., Nurgali K. (2015). …

If treating obesity with GLP-1-based therapies protects the heart, could it also prevent cancer or improve cancer outcomes? The case for randomized trials.

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… The SELECT trial (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) fundamentally redefined the treatment landscape for obesity. 1 In this large, event‐driven, randomized controlled trial (RCT) involving 17 604 adults with established cardiovascular disease and overweight or obesity … Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221‐2232. doi: 10.1056/NEJMoa2307563 2. Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity. …

Сердечная недостаточность с сохранившейся фракцией выброса: синергия между кардиологическими и экстракардиальными механизмами и эффекты новых методов лечения.

Сердечная недостаточность с консервированной фракцией выброса (HFFEF) является системным заболеванием, в котором метаболические коморбиды ожирение, тип 2 диабет (T2D) и хронические заболевания почек (CKD) сходятся, вызывая системное воспаление, эндотелиальную дисфункцию и миокардный фиброз. Микроваскулярная дисфункция представляет собой важную связь между этими коморбидами и аномалиями внутри и за пределами сердца, хотя ее причинно-следственная связь с ГФФФ по-прежнему не до конца установлена. Помимо поощрения миокардной жесткости и диастотической дисфункции, поврежденная микроваскулярная функ

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… In the STEP-HFpEF trial, treatment with semaglutide was also associated with an improvement in quality of life, as well as a substantial reduction in body weight (− 10.7 kg) after 52 weeks (Table 4 ). … Treatment with semaglutide resulted in a 24% RRR for the composite kidney endpoint, defined as progression to dialysis or transplantation, an eGFR < 15 mL/min/1.73 m², a ≥ 50% decline in eGFR from baseline, or death from kidney-related or cardiovascular causes (Table 4 ). …

Помимо потери веса: изучение неврологических последствий изменённой микробиоты кишечника послекариатрической хирургии.

В настоящем обзоре обсуждаются результаты, связанные с неврологическими расстройствами, кишечной микробиотой и бариатрической хирургией, с уделением особого внимания нейротрансмиттерам, нейроэндокрину, патофизиологии бактерий, способствующих возникновению нарушений, и возможным терапевтическим вмешательствам. Исследования в области нейротрансмиттеров показывают, что их уровни сильно зависят от кишечного микробиота, которая может связать их с такими неврологическими расстройствами, как болезнь Альцгеймера, болезнь Паркинсона, множественный склероз, депрессия и расстройства спектра аутизма. Пато

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… In addition, semaglutide was also found to improve the integrity of the gut barrier and reverse dysbiosis. … For example, research on the effects of semaglutide in obese mice showed that the treatment not only improved cognition and reduced inflammation but also significantly modified the gut microbiota. …

Efficacy of lifestyle modification combined with GLP-1 receptor agonists on body weight and cardiometabolic biomarkers in individuals with overweight or obesity: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established treatments for obesity. However, it remains inconclusive wh … in cholesterol (MD: -0.14 mg/dL, 95% CI: -1.05, 0.76, P = 0.750). Longer treatment duration, use of semaglutide or tirzepatide, weekly dosing, and studies conducted in North America showed more pronounced weight loss effects. Risk of bias assessment indicated no high-risk studies among the included trials. The GRADE assessment indicated a range of certainty f …

A Scoping Review of GLP-1 Receptor Agonists: Are They Associated with Increased Gastric Contents, Regurgitation, and Aspiration Events?

Background: The increased popularity and ubiquitous use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of diabet … rospective, five case series, and nine case reports. The GLP-1 RAs reported in the studies included semaglutide, liraglutide, lixisenatide, dulaglutide, tirzepatide, and exenatide. All studies, except one case report, reported patients with confounding factors for retained gastric contents and aspiration, such as a history of diabetes, cirrhosis, hypothyroidi …

Obesity Management in Adults: A Review.

IMPORTANCE: Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiova … Food and Drug Administration for long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide and liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, and orlistat. Of these, tirzepatide has the greatest effect, with mean weight loss of 21% at 72 weeks. E …

Comparison of IBD-related outcomes in patients with obesity treated with GLP-1 receptor agonists versus bariatric surgery.

INTRODUCTION: The global prevalence of obesity is rising, paralleled by an increase in IBD (inflammatory bowel disease). While studies exami … ohort was divided into two groups: patients with obesity and IBD prescribed GLP-1 RAs (dulaglutide, semaglutide, liraglutide, lixisenatide, exenatide, albiglutide, or tirzepatide) who had not undergone BS, and patients with obesity and IBD who underwent BS but had not received GLP-1 RAs. To ensure active exposure, GLP-1 RA use required at least two prescripti …

Unpacking adiposity: a narrative critical appraisal of diverse obesity definitions.

BACKGROUND: Obesity is a complex, multifaceted chronic disease that poses a major global health challenge. Traditionally, population-level screening and follow-up have relied heavily on body mass index (BMI). Although BMI provides a simple, standardized measure for epidemiological studies, it does not account for individual variations in muscle mass, fat distribution, or metabolic health. Consequently, relying solely on weight-to-height ratios-even when supplemented with waist circumference, waist-to-hip ratio, or waist-to-height ratio-limits precise individual diagnosis and comprehensive heal

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… This trial showed that 72 weeks of treatment with tirzepatide was superior to treatment with semaglutide in reducing body weight and WC [ 80 ]. … This study assigned over 1,000 patients with biopsy-defined metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or 3 fibrosis to receive either once-weekly subcutaneous semaglutide (2.4 mg) or a placebo for 240 weeks, demonstrating that semaglutide improved liver histology [ 81 ]. …

Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая

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… -1 receptor agonist (GLP-1RA) for managing type 2 diabetes mellitus (T2DM) and weight loss. 16 , 17 Sales data from 2024 highlights the market dominance of semaglutide formulations, with semaglutide injections (Ozempic ® ) led peptide drug sales, totaling $138.90 hundred million USD. … Name Brand Names Indication Company 1 Semaglutide Ozempic Diabetes Novo Nordisk 2 Dulaglutide Trulitciy Diabetes Eli Lilly 3 Semaglutide Wegovy Weight Novo Nordisk 4 Tirzepatide Mounjaro Diabetes Eli Lilly 5 Semaglutide Rybelsus Diabetes Novo Nordisk 6 Insulin NovoRapid Diabetes Novo Nordisk Aspart 7 …

A geriatrician's approach to managing the complex older adult with obesity.

The prevalence of obesity in older adults is rapidly increasing due to the demographic shift occurring globally. Older adults with obesity face health care challenges due to multimorbidity, functional dependency, and disability. This population often has prior history of struggles through weight-loss attempts during the middle years of life. Therefore, weight-loss intervention needs a personalized approach, taking into consideration weight-loss attempts, relapse, and life events, including bariatric surgery, functional limitations, psychosocial status, and current residential environment. Raci

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… The Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) trial on semaglutide has demonstrated a 20% reduction in the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among adults aged >45 years (38.2% of the … Furthermore, the results of the Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial have shown that semaglutide at a lower dose of 1 mg weekly reduced the risk of clinically important kidney outcomes by 24% while slowing the chronic disease progression [ 35 ]. …

A Clinical Genetics-Driven Dual Diagnosis of Prader-Willi Syndrome Due to Mosaic Maternal UPD(15) and NOTCH3-Related CADASIL.

Maternal uniparental disomy of chromosome 15 [UPD(15)mat] and imprinting defects account for about 30% of cases of Prader-Willi syndrome (PWS). Mosaic UPD(15)mat is rare and may escape routine testing. We describe a 45-year-old male patient in whom persistent clinical suspicion of PWS was not genetically confirmed by repeated methylation-based analyses. Clinical manifestations included neonatal hypotonia with low birth weight, early hyperphagia, severe obesity, short stature, growth hormone deficiency, type 2 diabetes mellitus, dyslipidemia, and MASLD/MASH with compensated cirrhosis. He presen

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… The anti-obesity and antidiabetic treatments included metformin, acarbose, insulin, liraglutide, semaglutide, and high-dose semaglutide. High-dose semaglutide (2.4 mg weekly) was not associated with q meaningful reduction in appetite, weight, or HbA1c. …

Obesity Pillars roundtable: Excessive weight reduction with highly effective anti-obesity medications (heAOMs).

BackgroundHistorically, many anti-obesity medications (AOMs) were withdrawn from development and/or the market due to safety concerns. Another challenge was that, with some exceptions, most of these AOMs had limited weight reducing efficacy. Approved AOMs often did not meet the weight reduction expectations of either clinicians, or their patients. Currently, newer approved and investigational AOMs achieve greater weight reduction than older AOMs. This has prompted an emerging new challenge of "too much weight loss" with some of these highly effective anti-obesity medications (heAOM) - somethin

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… The escalation of prescription for semaglutide both on and off label for weight reduction is not primarily driven by specialty obesity medicine clinicians. … While it may seem counterintuitive, for anyone on semaglutide or other heAOMs, I have implemented a “minimum intake” guideline and thus I do not typically endorse a Very Low Calorie Diets. …

Polypharmacology: new drugs in 2023-2024.

Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness,

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… Tirzepatide resembles semaglutide (which is a GLP1 receptor agonist only) in its therapeutic profile. … In quantitative terms, tirzepatide was superior to semaglutide both in the treatment of diabetes (reduction of glycated hemoglobin) [ 107 ] and overweight [ 108 ]. …

Clinical and Therapeutic Implications of Male Obesity.

The prevalence of obesity, a disorder linked to numerous comorbidities and metabolic complications, has recently increased dramatically worldwide and is highly prevalent in men, even at a young age. Compared to female patients, men with obesity more frequently have delayed diagnosis, higher severity of obesity, increased mortality rate, and only a minority of obese male patients are successfully treated, including with bariatric surgery. The aim of this review was to present the current state of knowledge about the clinical and therapeutic implications of obesity diagnosed in males.

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… Currently, five drugs are approved for weight-reduction therapy (orlistat, naltrexone/bupropion, 3 mg liraglutide, 2.4 mg semaglutide, phentermine/topiramate). … Among many GLP-1 agonists approved for the treatment of type 2 diabetes mellitus, only liraglutide 3.0 mg once-daily and semaglutide 2.4 mg once-weekly have been approved for obesity management. …

Sex- and Gender-Related Differences in Obesity: From Pathophysiological Mechanisms to Clinical Implications.

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue wei

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… Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325:1403. doi: 10.1001/jama.2021.1831. 136. … Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325:1414. doi: 10.1001/jama.2021.3224. 137. …

Optimisation or Restriction? Unpacking the Logic Behind NICE Decisions.

BackgroundThe National Institute for Health and Care Excellence (NICE) regularly issues optimised technology appraisal (TA) recommendations, whereby medicines are recommended for a subset of their licensed population. These decisions play a growing role in shaping patient access, yet the underlying drivers and implications of optimisation remain poorly understood.MethodsWe conducted a mixed‑methods analysis of all optimised NICE TAs published in 2023 and 2024. Fifty‑six appraisals met our inclusion criteria for qualitative assessment of committee documentation, while 30 provided sufficient dat

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… TA1021 Matching NHS England service delivery “The committee noted that tier 2 services could not support delivery of semaglutide. […] Therefore, the committee agreed that semaglutide should only be available within a specialist weight management service. … TA1021 Matching NHS England service delivery | “The committee noted that tier 2 services could not support delivery of semaglutide. […] Therefore, the committee agreed that semaglutide should only be available within a specialist weight management service. …