Pharmacological Treatment Of Obesity Research Articles

Will Tirzepatide become a game-changer in the pharmacological treatment of obesity? - literature review

Introduction and objective: Obesity has become an important public health issue in Poland. Furthermore, it is one of the most common preventable causes of diseases and mortality. Pharmacological methods of treating obesity have been developing significantly in recent years.Tirzepatide is a new dual incretin receptor agonist that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. The aim of this review is to assess the effectiveness of this medication in reducing body weight. Current state of knowledge: According to data from the Central Statistical Office (GUS) in Poland, 65% of men and 49% of women are struggling with the issue of excessive body weight [1]. Obesity in Polish society is steadily increasing in every age group. However, it affects most significantly children aged 7-13 years and adolescents. In 2022, the novel dual GLP and GIP-1 agonist has been registered for the treatment of type 2 diabetes which is not satisfactorily controlled. It can be also used together with diet and physical activity in patients diagnosed with obesity (BMI of 30 kg/m2 or more) or who are overweight (BMI 27-30 kg/m2) and have weight-related health problems such as hypertension, metabolic syndrome, dislipidaemia and diabetes mellitus [2]. Summary: The increasing prevalence of obesity leads to a dynamic search for the most effective pharmacological methods of treating obesity. The combined activation of GLP-1 and GIP receptors by Tirzepatide has been shown to have additional benefits beyond satisfying glucose control. The biological mechanism of action of this medication additionally causes decreased food intake, slowed gastric emptying and enhanced insulin secretion, all of which can contribute to weight reduction.

Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (− 22.05 kg [− 28.86; − 15.23), total cholesterol (− 0.88 [− 1.59; − 0.17]), triglycerides (− 0.70 [− 0.82; − 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (− 4.49 [− 7.65; − 1.33]), diastolic pressure (− 2.28 [− 4.25; − 0.31]), Hb glycated (− 0.97 [− 1.31; − 0.62]), HOMA IR (− 2.94; [− 3.52; − 2.35]) and cardiovascular risk (− 0.08; [− 0.10; − 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.

Pharmacological treatment of obesity in adults in Norway 2004-2022.

To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022. We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18-79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18-29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017. The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022. The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years.

Pharmacological treatment of obesity: an overview of different groups of anti-obesity drugs available in Poland

Introduction and Objective: Obesity, as one of the diseases of civilization, has become a significant problem in our time. Although the first ways of treating it appeared many years ago, pharmacotherapy of obesity has been developing significantly in recent years. The purpose of this article is to introduce the obesity drugs that have been registered for the treatment of obesity in Poland and to describe a new substance called tirzepatide, which, although it does not have such registration yet, is one of the most promising medications of the near future. State of Knowledge: Obesity is an urgent and growing problem. In Poland, about 25% of adults are obese, and this number is increasing over the years. In Europe, four drugs belonging to three different groups are registered for the treatment of obesity: orlistat, a combined drug that includes naltrexone hydrochloride and bupropion hydrochloride, liraglutide, and semaglutide. Although the last drug achieves the best results in studies and is the substance most favored by doctors and patients, there is still much research on new substances and formulations, which would bring even better results and health benefits. One of these substances is tirzepatide, a drug registered in 2022 for the treatment of type 2 diabetes. Summary: Nowadays in Poland, there are four drugs registered for obesity. Two of them are representatives of the group of GLP-1 analogues. Pharmacological treatment of obesity has good results and is a relatively safe process that should be implemented in conjunction with lifestyle changes. The fifth substance described in this article is tirzepatide, a drug that, although not registered for the treatment of obesity yet, is for now one of the most promising substances among the new drugs.

Pharmacological Approaches to Nonalcoholic Fatty Liver Disease: Current and Future Therapies.

Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), can promote the development of cirrhosis, hepatocellular carcinoma, cardiovascular disease, and type 2 diabetes. Similarly, type 2 diabetes confers the greatest risk for the development of NASH, especially when associated with obesity. Although lifestyle changes are critical to success, early implementation of pharmacological treatments for obesity and type 2 diabetes are essential to treat NASH and avoid disease progression. This article reviews current guidance regarding the use of pharmacological agents such as pioglitazone, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors in the setting of NAFLD and NASH. It also reviews the latest information on new drugs currently being investigated for the treatment of NASH.

Impact on weight loss and body composition of a food education intervention associated with Liraglutide treatment to address obesity

clinical practice guidelines recommend considering pharmacological treatment of obesity only as a complement to lifestyle modification. Drugs alone are usually ineffective in the long term after discontinuation, so pharmacological weight loss strategies should always be accompanied by lifestyle modifications. to analyze the changes in weight, body mass index and body composition by means of electrical bioimpedance after a 32-week treatment with liraglutide in patients with obesity, associated or not with a food education program. the study involved 68 patients who were randomly divided into 2 groups. One group received treatment with liraglutide 3.0 mg/day along with individual dietary education, and the other group was treated with liraglutide 3.0 mg/day and standard medical follow-up for 32 weeks. The data collected were weight (kg), height (m) (Seca® brand), body mass index (kg/m2) and body composition using multifrequency bioimpedance (SECA 112® brand). The variables were analyzed at the beginning and at the end of the treatment. after 32 weeks of treatment, both study groups lost weight significantly. The group treated with liraglutide and individual dietary education had a reduction of 8.77 kg (9.08 %) (p < 0.001) and the group treated with liraglutide without education had a reduction of 3.55 kg (3.45 %) (p < 0.001). The BMI of the participants treated with liraglutide and education decreased by -4,04 kg/m2 (10.35 %) (p < 0.001) and in the group without education it decreased by -3.22 kg/m2 (8.30 %) (p = 0.003). In the educated group, fat mass decreased by -7.65 kg (15.89 %) (p < 0.001), although skeletal muscle mass also decreased by -1.62 kg (6.8 %) (p < 0.001). In those treated with liraglutide without education, a reduction in fat mass and skeletal muscle mass was also observed - fat mass by -4.72 kg (9.43 %) (p < 0.001) and skeletal muscle mass by -0.17 kg (0.70 %) (p < 0.001). Differences were also observed between groups, observing a greater reduction in weight, BMI, fat mass and skeletal muscle mass in the group with liraglutide and education compared to the group without education, although these differences were not statistically significant. dietary education associated with liraglutide treatment may contribute to increasing weight loss and fat mass. However, it was also associated with an unwanted loss of skeletal muscle mass, probably related to the greater intensity of weight loss, which will have to be reversed in future therapeutic approaches. Habit modification through multidisciplinary treatment, including nutritional education, combined strength and resistance exercise, and cognitive-behavioral therapy, could be an effective way to treat obesity and maintain weight, body composition, and adherence to a lifestyle.

Anti-obesity Medication Use for Adolescent Metabolic and Bariatric Surgery Patients: A Systematic Literature Review.

Bariatric surgery, in combination with pharmacotherapy, has been proven to be successful incombatting weight regain in adults; however, the useof anti-obesity medications to augment weight loss in adolescents before and after bariatric surgery is not well studied.In adolescent obese patients, the efficacy of anti-obesity pharmacotherapy before and after bariatric surgery on weight loss compared to no interventions in various studies was investigated. A PubMed literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identifystudies related to the pharmacologic treatment of obesity in adolescents with a history of bariatric surgery. Inclusion criteria consisted of clinical trials, case reports, case series, chart reviews, systematic reviews, and meta-analyses written in English and published between 2005 and 2022 using our search criteria. Exclusion criteria were studies that investigated adults, did not include pharmacotherapy, and were not relevant to the outcome of interest. The initial search yielded 1275 results, which was reduced to 879 after removal of duplicates. After applying exclusion criteria, the number of articles was reduced to 63.Full articles were examined and 44 were excluded due to relevance. Nineteen articles were included in the qualitative analysis. A total of 2471 adolescents were treated with various types of pharmacotherapy, 65 of whom had a history of bariatric surgery. The results showed varied effects of pharmacotherapy with the different medications studied. However, the 65 patients were included in cohorts of patients with no history of bariatric surgery. These studies did not include data specific to adolescent bariatric surgery patients. There is a wealth of evidence highlighting the efficacy of pharmacotherapy in assisting with weight loss in adolescents with obesity; however, our literature search showed a lack of studies focusing on the use of pharmacotherapy in the adolescent bariatric surgery population. Potential limitations include missing studies in our literature search, the variability in methods between studies, and the lack of standardized quality assessment. Additionally, studies involving our objective of choice regardingbariatric surgery with anti-obesity medication were limited. Clinical trials to determine the efficacy of medications as an adjunct to bariatric surgery in preventing weight regain and leading to optimal weight loss in this population are of utmost importance.

Consensus on pharmacological treatment of obesity in Latin America.

A panel of 10 experts in obesity from various Latin American countries held a Zoom meeting intending to reach a consensus on the use of anti-obesity medicines and make updated recommendations suitable for the Latin American population based on the available evidence. A questionnaire with 16 questions was developed using the Patient, Intervention, Comparison, Outcome (Result) methodology, which was iterated according to the modified Delphi methodology, and a consensus was reached with 80% or higher agreement. Failure to reach a consensus led to a second round of analysis with a rephrased question and the same rules for agreement. The recommendations were drafted based on the guidelines of the American College of Cardiology Foundation/American Heart Association Task Force on Practice. This panel of experts recommends drug therapy in patients with a body mass index of ≥30 or ≥27 kg/m2 plus at least one comorbidity, when lifestyle changes are not enough to achieve the weight loss objective; alternatively, lifestyle changes could be maintained while considering individual parameters. Algorithms for the use of long-term medications are suggested based on drugs that increase or decrease body weight, results, contraindications, and medications that are not recommended. The authors concluded that anti-obesity treatments should be individualized and multidisciplinary.

Treatment of obesity. A review of selected guidelines

Treatment of obesity is one of the challenges of the 21st century. It is a risk factor for the development of other diseases such as hypertension, coronary heart disease and cancer. The diagnosis of obesity should be based on body mass measurements, taking into account height and sex. It is also recommended to measure waist and hip circumference. Lifestyle modifications, which include increased physical activity and reduced calorie intake, are the primary method of treating obesity. Unfortunately, changing habits is difficult and even unattainable for many patients. Due to the increasing prevalence of obesity in the society, this review of guidelines is addressed to general practitioners and all physicians who encounter obese patients in their practice. Each of the guidelines analysed emphasises prevention, early diagnosis, and treatment of obesity. Behavioural and dietary changes are central in obesity management. The guidelines also point to the role of effective doctor–patient communication, as well as the need for a multidisciplinary management of obesity by a team composed of a physician, dietitian, and often physiotherapist. Pharmacotherapy, which was introduced in recent years as a supportive treatment, is another pillar of obesity therapy. Therefore, we also reviewed guidelines regarding pharmacological treatment of obesity. We focused on summarising indications for anti-obesity medications, descriptions of individual medications, their dosing regimens, as well as therapeutic goals, pointing out differences between individual recommendations.

Eligibility for obesity management in Peru: Analysis of National Health Surveys from 2014 to 2022

Background: The prevalence of overweight and obesity has increased fastest in low- and middle-income countries in the last decades. Together with this rising prevalence, pharmacological and surgical interventions for obesity have emerged. How many people need these treatments is unknown. We quantified the prevalence of people in need of pharmacological and surgical treatment for obesity in Peru between 2014 and 2022. Methods: Repeated cross-sectional analysis of national health surveys in Peru was conducted. Eligibility for pharmacological treatment for obesity was: body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 alongside type 2 diabetes or hypertension (self-reported). Eligibility for bariatric surgery were BMI ≥40 kg/m2 or BMI between 35 to 39.9 kg/m2 linked to weight-related health problems. We used Poisson regressions to identify associated factors with eligibility for obesity management. Results: Across years, 260,131 people (mean age 44.0 and 54.5% were women) were studied, 66,629 (27.7%; 95% CI: 27.4% - 28.1%) were eligible for obesity medication, and 5,263 (2.5%; 95% CI: 2.4% - 2.6%) were eligible for bariatric surgery. Female sex, older age, higher socioeconomic level and study year were associated with higher probability of eligibility for both obesity medication and bariatric surgery. Conclusions: Eligibility for obesity management has increased over time in Peru. There is a need to strengthen policies to tackle overweight and obesity in Peru, acknowledging that some individuals may benefit from pharmacological and surgical interventions.

Obesity-related hypertension and chronic kidney disease: from evaluation to management.

With the recent obesity pandemic, obesity-related hypertension and its complications (e.g., heart failure, coronary disease, and chronic kidney disease [CKD]) are gaining attention in clinical and research fields. Obesity-related hypertension frequently precedes the onset of CKD and aggravates its progression. In this review, we discuss the role of visceral fat in the pathophysiology of obesity-related hypertension and the potential therapeutic strategies for its prevention and management. Various factors, including the sympathetic nervous system, renin-angiotensin-aldosterone system, and inflammatory pathways, are intricately involved in the pathogenesis of obesity-related hypertension. These factors individually and jointly contribute to the development of hypertension (usually sodium-sensitive or resistant hypertension) and, ultimately, to the progression of CKD. From a clinical standpoint, a decline in renal function in advanced CKD further makes blood pressure control challenging since only a few options are available for blood pressure-lowering medications. Proactive lifestyle modification, pharmacological treatment for obesity, and bariatric surgery can be considered for obesity control and management. Furthermore, intensive blood pressure control is required to prevent and halt the development and progression of CKD.

Eligibility for obesity management in Peru: Analysis of National Health Surveys from 2014 to 2022

Background: The prevalence of overweight and obesity has increased fastest in low- and middle-income countries in the last decades. Together with this rising prevalence, pharmacological and surgical interventions for obesity have emerged. How many people need these treatments is unknown. We quantified the prevalence of people in need of pharmacological and surgical treatment for obesity in Peru between 2014 and 2022. Methods: Repeated cross-sectional analysis of national health surveys in Peru was conducted. Eligibility for pharmacological treatment for obesity was: body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 alongside type 2 diabetes or hypertension (self-reported). Eligibility for bariatric surgery were BMI ≥40 kg/m2 or BMI between 35 to 39.9 kg/m2 linked to weight-related health problems. We used Poisson regressions to identify associated factors with eligibility for obesity management. Results: Across years, 260,131 people (mean age 44.0 and 54.5% were women) were studied, 66,629 (27.7%; 95% CI: 27.4% - 28.1%) were eligible for obesity medication, and 5,263 (2.5%; 95% CI: 2.4% - 2.6%) were eligible for bariatric surgery. Female sex, older age, higher socioeconomic level and study year were associated with higher probability of eligibility for both obesity medication and bariatric surgery. Conclusions: Eligibility for obesity management has increased over time in Peru. There is a need to strengthen policies to tackle overweight and obesity in Peru, acknowledging that some individuals may benefit from pharmacological and surgical interventions.

207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become standard-of-care for the pharmacological treatment of obesity by inducing clinically meaningful weight loss through a reduction in appetite. While these agents potently reduce fat mass, the caloric restriction also reduces skeletal muscle mass. Strategies to preserve skeletal muscle in the presence of caloric restriction are needed to improve weight loss quality in obese patents. Trevogrumab (∝-MSTN) and garetosmab (∝-ActA) are fully human monoclonal antibodies that potently inhibit two mediators of skeletal muscle atrophy: myostatin (MSTN) and activin A (ActA). We first tested the effects of ∝-MSTN, ∝-ActA and GLP-1RA (Semaglutide [Sema]) on body composition of diet-induced obese mice either alone or in combination. Sema (-29.8%) and ∝-MSTN/∝-ActA (-23.4%) produced significant reduction in fat mass after 4 weeks of treatment vs baseline. Adding MTSN and ActA blockade to Sema produced an additive effect on fat mass (-54.2%). This combination also increased lean mass by 9.8% vs a 1.9% loss with Sema alone. To test this in primates, we performed a 20-week study with the combined administration of either Sema + ∝-MSTN or Sema + ∝-MSTN and ∝-ActA in obese male cynomolgus monkeys. The combination of ∝-MSTN + Sema was sufficient to cause an additive effect on fat mass -43.9% vs -25.1% for Sema alone. The addition of ∝-ActA to the combination produced a similar reduction in fat (-49.6%). The Sema control group also lost -2.5% lean mass after 20 weeks; despite the significant reduction in fat mass, the addition of ∝-MSTN to Sema slightly increased lean mass over the same period (0.5%); the addition of ∝-ActA increased lean mass even further (6.2%). These data suggest the blockade of MSTN and ActA to GLP-1RA treatment could greatly improve the quality of weight loss with this class of anti-obesity agents. Disclosure J.Mastaitis: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. D.Gomez: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. V.Le rouzic: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. M.Stec: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. N.Khan: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. E.Na: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. T.Mcwilliams: None. S.Min: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. M.Sleeman: Employee; Regeneron Pharmaceuticals Inc. Funding Regeneron Pharmaceuticals Inc.

THE EFFECT OF SEMAGLUTIDE ON BLOOD PRESSURE IN PATIENTS WITHOUT DIABETES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: The interplay of hypertension and obesity is well described. Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). The aim of this review is to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. Design and method: This systematic review was performed in line with the 2020 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science. Studies were screened to include randomised controlled trials of semaglutide versus a placebo in adults without diabetes. Continuation of anti-hypertensive treatment was a secondary outcome. Pooled and sensitivity analyses were performed and risk of bias was assessed. Results: 611 potential studies were found by the search and 6 RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in SBP was -4.83 mmHg (95% CI -5.65 to -4.02) while that for DBP was -2.45 mmHg (95% CI -3.65 to -1.24). Only two studies (STEP 1, 4) reported change in anti-hypertensive medications. In STEP 1, 34.3% of those on anti-hypertensive medications, and receiving the intervention, either decreased or stopped these drugs, versus 16% in the placebo group. Equivalent figures were 25.5% and 11.9% for STEP 4. Critical appraisal revealed all included studies to be of a high methodological quality. Conclusions: The magnitude of BP reduction evident following semaglutide treatment in normotensive populations with obesity and without diabetes is clinically significant. The effect of semaglutide in those with obesity and hypertension is yet to be determined. Targeting excess body weight may be a novel therapeutic strategy for patients with difficult to control hypertension.

Management of weight loss in a patient with Prader-Willi syndrome with satietogenics: a case report

Objective: To report the evolution and therapeutic approach in a patient with PraderWilli Syndrome (PWS) associated with literature data assessment with a focus on the pharmacological treatment of obesity in patients with this pathology, since there are currently not many studies that contribute or name a strategy with the use of satietogenics. Methods: The present study was elaborated according to the rules of CARE case report. Due to the cognitive impairment present in the syndrome, the patient’s mother was first contacted about the writing of this paper and was given consent through the signing of the Free and Informed Assent Term for this paper. The patient was treated at a hospital-adjacent Nutrology outpatient clinic in 2019. Case Description: YSP, 20 years old, diagnosed with PWS and Grade III obesity (initial BMI of 55.4kg/m², 140kg) attended the Nutrology outpatient clinic of Adriano Jorge Hospital Foundation – FHAJ in 2019 under referral from a third party, and his companion (relative) reporting hyperphagia and poor school performance, initially without a nutrition plan, during follow-up, nutritional guidance and multi-professional care have been initiated. Results: During the follow-up of the years 2019-2021, resulting from the SARS-CoV-2 pandemic in Brazil and the consequent confinement, the patient presented worsening anxiety and hyperphagia, evolving with increased binge eating and discontinuation of physical activities and diet adherence. During the follow-up in the same period, there were 03 returns denoting weight maintenance, later (2021) the use of on-label (Sibutramine), off-label (Fluoxetine), and Metformin medications were associated with the therapeutic regimen for obesity, due to evidence of insulin resistance. Final considerations: The patient evolved with progressive weight loss and better adherence to the food plan and physical activities.

Farmakologiczne leczenie otyłości

Nadwaga i otyłość są przyczynami wielu chorób, takich jak cukrzyca II typu oraz choroby sercowo-naczyniowe. Z każdym nadmiarowym kilogramem masy ciała zwiększa się także ryzyko zachorowania na nowotwory m.in.: przełyku, nerki i trzustki, raka wątrobowokomórkowego czy raka wpustu żołądka. W ostatnich dekadach obserwowany jest wzrost liczby osób dotkniętych otyłością. Z tego powodu problem ten nazywany jest epidemią otyłości. Epidemia ta dotyka nie tylko osób dorosłych, ale także coraz młodsze dzieci. Regularna aktywność fizyczna oraz zmiana nawyków żywieniowych są podstawą leczenia otyłości lub nadwagi. W przypadku, gdy nie osiąga się zamierzonych celów terapeutycznych, możliwe jest włączenie leczenia farmakologicznego. Grupa leków na otyłość w lecznictwie ulega znacznej zmianie na przestrzeni lat. Wiele leków o tym wskazaniu, wprowadzanych do lecznictwa w XX i XXI wieku, zostało wycofanych z powodu odkrytych poważnych działań niepożądanych. Dotyczyło to fenterminy, mazindolu, sibutraminy i rimonabantu. Obecnie w Polsce do leczenia otyłości dostępne są cztery leki. Najstarszy z nich, orlistat, został wprowadzony do obrotu w roku 1998. Kombinacja naltreksonu z bupropionem oraz liraglutyd są dostępne od 2015 roku. Natomiast w 2021 roku zarejestrowano setmelanotyd, wykorzystywany jedynie w przypadku otyłości wynikającej z rzadkich chorób genetycznych. W niniejszym artykule dokonano przeglądu ich struktury chemicznej, mechanizmu działania, efektywności oraz działań niepożądanych. Ponadto opisano semaglutyd, drugi po liraglutydzie lek z grupy analogów hormonu inkretynowego, glukagonopodobnego peptydu 1. W Polsce jest on zarejestrowany tylko jako lek przeciwcukrzycowy, lecz w Stanach Zjednoczonych od roku 2021 stosowany jest w otyłości. Obecność tego leku w obrocie i obiecujące wyniki badań klinicznych powodują, że także w Polsce jest zapisywany poza wskazaniami rejestracyjnymi do leczenia otyłości. Nowe terapie leczenia otyłości dają nadzieję na skuteczne i mniej ryzykowne rozwiązanie problemu niż chirurgia bariatryczna. Należy pamiętać, że dopiero połączenie zdrowej diety, ćwiczeń fizycznych i leczenia farmakologicznego daje najlepsze i najtrwalsze efekty w leczeniu otyłości.

Obesity and cardiovascular disease: An executive document on pathophysiological and clinical links promoted by the Italian Society of Cardiovascular Prevention (SIPREC).

The prevalence of obesity worldwide has increased in recent decades not only among adults, but also in children and adolescents. This phenomenon contributes to an increased risk of cardiovascular diseases (CVD), also after the adjustment for conventional risk factors such as hypertension, diabetes and dyslipidemia. Indeed, obesity contributes to the development of insulin resistance, endothelial dysfunction, sympathetic nervous system activation, increased vascular resistance and inflammatory and prothrombotic state which promote the incidence of major cardiovascular events. On the basis of this evidence, in 2021 obesity has been acknowledged as a definite pathological identity and identified as a recurrent, chronic non-communicable disease. Therapeutic strategies for the pharmacological treatment of obesity include the combination of naltrexone and bupropione and the lipase inhibitor orlistat and they have been recently implemented with the glucagon like peptide-1 receptor agonists semaglutide and liraglutide, which have produced positive and sustained effects on body weight reduction. If drug interventions are not effective, bariatric surgery may be considered, representing an efficacious treatment option for extreme obesity or obesity with comorbidities. The present executive paper is aimed to increase knowledge on the relationships between obesity and CVD, to raise the perception of this condition which is currently insufficient and to support the clinical practice management.

Pharmacologic Treatment of Obesity in Reproductive Aged Women.

This report will review existing literature on weight loss outcomes for various anti-obesity medications (AOMs) as well as their effects on human fertility, pregnancy, or breastfeeding. There is a paucity of research on the effects of AOMs on human pregnancy and fertility. The majority of AOMs are not recommended during pregnancy and breastfeeding due to known or unclear risks of harm to offspring. As the prevalence of obesity rises, AOMs have proven to be effective tools for weight loss in the general adult population. When prescribing AOMs to reproductive-aged women, providers should consider both the cardiometabolic benefits of these medications and potential effects that AOMs might have on hormonal contraception, pregnancy, or breastfeeding. Animal studies in rats, rabbits, and monkeys have suggested teratogenic effects of several medications discussed in this report. However, a lack of data on the use of many AOMs during human pregnancy or lactation makes it difficult to comment on the safety of their use in these time periods. Some AOMs show promise in promoting fertility while others might decrease the efficacy of oral contraceptives, highlighting some of the special considerations that must be taken when prescribing AOMs to reproductive-aged women. More research into the risks and benefits of AOMs in the context of reproductive-aged women's unique healthcare needs is an important step in improving this population's access to effective treatments for obesity.

Off-label pharmacological treatment of obesity: a systematic review of clinical studies

Introduction: There are 2.0 billion overweight and obese people in the world, and Brazil ranks fifth in the world. The World Health Organization (WHO) advises that the use of drugs to combat obesity is indicated for patients who have a body mass index (BMI) above 30 kg/m2 or when the BMI is 25 kg/m2 associated with comorbidities. that permeate excess weight. A variety of drug classes approved for other indications have been used off-label in an attempt to promote weight loss. Objective: It was to list and present the main off-label drugs for obesity in adults, as well as to show the scientific evidence of clinical studies. Methods: The present study followed a concise systematic review (PRISMA) model. The literary search process was carried out from July 2022 to September 2022 and was developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar, using scientific articles from 2002 to 2022. The low quality of evidence was attributed to reports of cases, editorials, and brief communications, according to the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument using the Funnel Plot. Results and Conclusion: We found 98 studies that underwent eligibility analysis, and then 15 of the 12 total studies were selected. Most studies showed homogeneity in their results, with I2 =96.5% &gt;50%. The Funnel Plot showed a symmetrical behavior, not suggesting a significant risk of bias in the studies. Off-label prescribing is very common among physicians who treat obesity. However, randomized controlled studies should be increasingly encouraged and increased to clearly present the scientific evidence and, thus, propose a scientific formalism for the safe and effective use of off-label anti-obesity drugs. Physicians, however, have adopted a more pragmatic approach, giving much greater credibility to shared clinical experience, particularly in situations where favorable outcomes have been consistently observed over decades. International medical bodies do not recommend the off-label use of drugs approved for the exclusive use of weight loss. In Brazil, the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) recommends that drugs approved for the treatment of obesity be prescribed preferentially over off-label treatments. In addition, the patient must be well informed and aware that the drug is not approved by Anvisa for this indication or chronic use.

The Effect of Semaglutide on Blood Pressure in Patients without Diabetes: A Systematic Review and Meta-Analysis.

(1) Background: Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). This review aimed to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. (2) Methods: Relevant studies were identified via a search of research databases. Studies were screened to include randomized controlled trials (RCTs) of semaglutide versus a placebo in adults. Pooled and sensitivity analyses were performed, and risk of bias was assessed. (3) Results: six RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in systolic BP was -4.83 mmHg (95% CI: -5.65 to -4.02), while that for diastolic BP was -2.45 mmHg (95% CI: -3.65 to -1.24). All included studies were of a high methodological quality. (4) Conclusions: A clinically significant reduction in BP was evident following semaglutide treatment in normotensive populations without diabetes. The effect of semaglutide in those with obesity and hypertension is as yet undetermined. Targeting excess body weight may be a novel therapeutic strategy for these patients.