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Pharmacology & Therapeutics Nov 2023Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure and non-alcoholic liver disease are a major health and economic... (Review)
Review
Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure and non-alcoholic liver disease are a major health and economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy and safety. This article provides a comprehensive overview of obesity and its comorbidities, with a special focus on organ-specific pathomechanisms. Bariatric surgery as the so far most-effective therapeutic strategy, current pharmacological treatment options and future treatment strategies will be discussed. An increasing knowledge about the gut-brain axis and especially the identification and physiology of incretins unfolds a high number of potential drug candidates with impressive weight-reducing potential. Future multi-modal therapeutic concepts in obesity treatment may surpass the effectivity of bariatric surgery not only with regard to weight loss, but also to associated comorbidities.
Topics: Humans; Diabetes Mellitus, Type 2; Obesity; Bariatric Surgery; Comorbidity; Incretins; Weight Loss
PubMed: 37879540
DOI: 10.1016/j.pharmthera.2023.108549 -
Lancet (London, England) May 2023Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial.
METHODS
We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365.
FINDINGS
Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management.
INTERPRETATION
Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH.
FUNDING
Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy.
Topics: Humans; Obesity, Morbid; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Gastric Bypass; Bariatric Surgery; Life Style; Laparoscopy; Gastrectomy; Treatment Outcome
PubMed: 37088093
DOI: 10.1016/S0140-6736(23)00634-7 -
Chirurgie (Heidelberg, Germany) Jun 2023
Topics: Humans; Bariatric Surgery; Obesity, Morbid
PubMed: 37212897
DOI: 10.1007/s00104-023-01839-4 -
Wiener Klinische Wochenschrift Nov 2023Bariatric surgery results in significant weight loss, reduction or even remission of obesity-associated comorbidities, reduced mortality, and improved quality of life in...
Bariatric surgery results in significant weight loss, reduction or even remission of obesity-associated comorbidities, reduced mortality, and improved quality of life in many patients; however, obesity is a chronic disease, thus follow-up care is required after bariatric surgery. Furthermore, specific issues, such as micronutrient deficiencies and subsequent complications, can arise both in the short-term and the long-term. Abdominal pain after bariatric surgery must always be regarded as a serious symptom. A further focus should be on the diagnosis and treatment of dumping syndrome. Patients with type 2 diabetes should be regularly screened for recurrent hyperglycemia as well as specific sequelae, even though blood glucose levels may be substantially improved or normalized. In addition to centers with multidisciplinary teams, primary care and, in particular, general practitioners will play an increasingly more important role in the follow-up care after bariatric surgery.
Topics: Humans; Diabetes Mellitus, Type 2; Quality of Life; Obesity; Bariatric Surgery; Malnutrition; Obesity, Morbid; Postoperative Complications
PubMed: 37821696
DOI: 10.1007/s00508-023-02272-7 -
Clinical Medicine (London, England) Jul 2023Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in... (Review)
Review
Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormone-based pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications. Tirzepatide, a dual agonist of GLP1 and GIP receptors, marks a new era in obesity pharmacotherapy in which a combination of gut hormones could approach the WL achieved with bariatric surgery. In this review, we discuss emerging obesity treatments with a focus on gut hormone combinations and the concept of a multimodal approach for obesity management.
Topics: Humans; Diabetes Mellitus, Type 2; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Obesity; Bariatric Surgery; Weight Loss
PubMed: 37524416
DOI: 10.7861/clinmed.2023-0144 -
Obesity Surgery Jan 2024This survey of international experts in obesity management was conducted to achieve consensus on standardized definitions and to identify areas of consensus and...
INTRODUCTION
This survey of international experts in obesity management was conducted to achieve consensus on standardized definitions and to identify areas of consensus and non-consensus in metabolic bariatric surgery (MBS) to assist in an algorithm of clinical practice guidelines for the management of obesity.
METHODS
A three-round Delphi survey with 136 statements was conducted by 43 experts in obesity management comprising 26 bariatric surgeons, 4 endoscopists, 8 endocrinologists, 2 nutritionists, 2 counsellors, an internist, and a pediatrician spanning six continents over a 2-day meeting in Hamburg, Germany. To reduce bias, voting was unanimous, and the statements were neither favorable nor unfavorable to the issue voted or evenly balanced between favorable and unfavorable. Consensus was defined as ≥ 70% inter-voter agreement.
RESULTS
Consensus was reached on all 15 essential definitional and reporting statements, including initial suboptimal clinical response, baseline weight, recurrent weight gain, conversion, and revision surgery. Consensus was reached on 95/121 statements on the type of surgical procedures favoring Roux-en-Y gastric bypass, sleeve gastrectomy, and endoscopic sleeve gastroplasty. Moderate consensus was reached for sleeve gastrectomy single-anastomosis duodenoileostomy and none on the role of intra-gastric balloons. Consensus was reached for MBS in patients > 65 and < 18 years old, with a BMI > 50 kg/m, and with various obesity-related complications such as type 2 diabetes, liver, and kidney disease.
CONCLUSIONS
In this survey of 43 multi-disciplinary experts, consensus was reached on standardized definitions and reporting standards applicable to the whole medical community. An algorithm for treating patients with obesity was explored utilizing a thoughtful multimodal approach.
Topics: Adolescent; Aged; Humans; Bariatric Surgery; Consensus; Delphi Technique; Diabetes Mellitus, Type 2; Gastrectomy; Gastric Bypass; Obesity; Obesity Management; Obesity, Morbid; Practice Guidelines as Topic
PubMed: 37999891
DOI: 10.1007/s11695-023-06913-8 -
Journal of Endocrinological... Feb 2024There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on... (Review)
Review
PURPOSE
There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on anthropometric characteristics and nutritional and pharmacological aspects of obesity from a gender perspective.
METHODS
A literature search within PubMed was performed. Selected publications related to obesity and gender differences were reviewed.
RESULTS
The prevalence of obesity among men is higher than in women, but women have a higher percentage of body fat content compared to men, and gender appears to be an important factor in the manifestation of central (android) or peripheral (gynoid) obesity. In addition, while in most clinical trials, women are still underrepresented, in clinical registration trials of anti-obesity drugs, women are commonly up-represented and gender-specific analysis is uncommon. Considering that adipose tissue is one of the factors affecting the volume of distribution of many drugs, mainly lipophilic drugs, gender differences might be expected in the pharmacokinetics and pharmacodynamics of anti-obesity drugs. Indeed, although Liraglutide 3 mg, a long-acting glucagon-like peptide-1 receptor agonist, and naltrexone/bupropion display lipophilic properties, currently, a gender-dose adjustment for both these drugs administration is not recommended. In addition, despite that predicted responders to treatment offer substantial opportunities for efficient use, especially of expensive new therapies, such as anti-obesity drugs, data on gender differences to identify early responders to both these have not yet been investigated. Finally, bariatric surgery gender disparity reflects healthcare practices. Weight loss similar, but differing effects: women need more correction and face psychology challenges; men have worse physiology and fewer comorbidity improvements.
CONCLUSION
Gender differences exist in obesity prevalence and phenotype, body fat distribution, drug efficacy, clinical trial representation, and different secondary effects of bariatric surgery. Gender is an important variable in obesity analysis.
Topics: Male; Female; Humans; Obesity; Anti-Obesity Agents; Weight Loss; Liraglutide; Bariatric Surgery
PubMed: 37740888
DOI: 10.1007/s40618-023-02196-z -
Frontiers in Endocrinology 2023Obesity has been associated with depressive symptoms and impaired cognition, but the mechanisms underlying these relationships are not well understood. It is also not...
BACKGROUND
Obesity has been associated with depressive symptoms and impaired cognition, but the mechanisms underlying these relationships are not well understood. It is also not clear whether reducing adiposity reverses these behavioral outcomes. The current study tested the impact of bariatric surgery on depressive symptoms, cognition, and the brain; using a mediation model, we also examined whether the relationship between changes in adiposity after the surgery and those in regional thickness of the cerebral cortex are mediated by changes in low-grade inflammation (as indexed by C-reactive protein; CRP).
METHODS
A total of 18 bariatric patients completed 3 visits, including one baseline before the surgery and two post-surgery measurements acquired at 6- and 12-months post-surgery. Each visit consisted of a collection of fasting blood sample, magnetic resonance imaging of the brain and abdomen, and assessment of depressive symptoms and cognition.
RESULTS
After surgery, we observed reductions of both visceral fat (p< 0.001) and subcutaneous fat (p< 0.001), less depressive symptoms (p< 0.001), improved verbal reasoning (p< 0.001), and reduced CRP (p< 0.001). Mediation analyses revealed that the relationships between the surgery-related changes in visceral fat and cortical thickness in depression-related regions are mediated by changes in CRP (ab=-.027, SE=.012, 95% CI [-.054, -,006]).
CONCLUSION
These findings suggest that some of the beneficial effects of bariatric surgery on brain function and structure are due to a reduction of adiposity-related low-grade systemic inflammation.
Topics: Humans; Depression; Inflammation; Brain; Obesity; Bariatric Surgery; Cognition
PubMed: 37484955
DOI: 10.3389/fendo.2023.1171244 -
Medicina (Kaunas, Lithuania) Jun 2023Alarming statistics show that the number of people affected by excessive weight has surpassed 2 billion, representing approximately 30% of the world's population. The... (Review)
Review
Alarming statistics show that the number of people affected by excessive weight has surpassed 2 billion, representing approximately 30% of the world's population. The aim of this review is to provide a comprehensive overview of one of the most serious public health problems, considering that obesity requires an integrative approach that takes into account its complex etiology, including genetic, environmental, and lifestyle factors. Only an understanding of the connections between the many contributors to obesity and the synergy between treatment interventions can ensure satisfactory outcomes in reducing obesity. Mechanisms such as oxidative stress, chronic inflammation, and dysbiosis play a crucial role in the pathogenesis of obesity and its associated complications. Compounding factors such as the deleterious effects of stress, the novel challenge posed by the obesogenic digital (food) environment, and the stigma associated with obesity should not be overlooked. Preclinical research in animal models has been instrumental in elucidating these mechanisms, and translation into clinical practice has provided promising therapeutic options, including epigenetic approaches, pharmacotherapy, and bariatric surgery. However, more studies are necessary to discover new compounds that target key metabolic pathways, innovative ways to deliver the drugs, the optimal combinations of lifestyle interventions with allopathic treatments, and, last but not least, emerging biological markers for effective monitoring. With each passing day, the obesity crisis tightens its grip, threatening not only individual lives but also burdening healthcare systems and societies at large. It is high time we took action as we confront the urgent imperative to address this escalating global health challenge head-on.
Topics: Animals; Obesity; Bariatric Surgery
PubMed: 37374323
DOI: 10.3390/medicina59061119 -
Archives of Gynecology and Obstetrics May 2024Obesity is a global health issue that has grown to epidemic proportions. According to World Health Organisation (WHO), overweight and obesity are responsible for more... (Review)
Review
Obesity is a global health issue that has grown to epidemic proportions. According to World Health Organisation (WHO), overweight and obesity are responsible for more than 1.2 million deaths in Europe each year, representing > 13% of the region's total mortality. Highly processed, calorie-dense foods and reduced physical activity are considered as primary drivers of obesity, but genetic predisposition also plays a significant role. Notably, obesity is more prevalent in women than in men in most countries, and several obesity-related comorbidities exhibit sex-specific pathways. Treatment indication depends on BMI (body mass index), as well as existing comorbidities and risk factors. To reduce obesity-associated comorbidities, a permanent reduction in body weight of (at least) 5-10% is recommended. Treatment guidelines suggest an escalating stepwise approach including lifestyle intervention, pharmacotherapy, and bariatric-metabolic surgery. As cumulative evidence suggests differences in weight loss outcomes, there is growing interest in sex-specific considerations in obesity management. However, most trials do not report weight loss or changes in body composition separately for women and men. Here, we discuss state-of-the-art obesity management and focus on current data about the impact of sex on weight loss outcomes.
Topics: Male; Female; Humans; Obesity; Body Weight; Overweight; Bariatric Surgery; Weight Loss
PubMed: 38329549
DOI: 10.1007/s00404-023-07367-0