Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment. METHODS: This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%). RESULTS: We included 124 patients: 62 in the AOM/AI group (63.6 ± 10 years, body mass index [BMI] 34.3 ± 7.1 kg/m2) and 62 in the AOM group (62.8 ± 9.9 years, BMI 34.6 ± 6.5 kg/m2). The mean time of follow up was 9.3 ± 3.5 months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12 months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12 months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. CONCLUSIONS: The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.

Current perspectives in obesity management: unraveling the impact of different therapy approach in real life obesity care.

BACKGROUND: The challenge of addressing obesity persists in healthcare, necessitating nuanced approaches and personalized strategies. This study aims to evaluate the effects of diverse therapeutic interventions on anthropometric and biochemical parameters in individuals with overweight and obesity within a real-world clinical context. METHODS: A retrospective analysis was conducted on 192 patients (141 females, 51 males) aged 18 to 75, with a BMI ranging from 25 to 30 (14.1%) and BMI ≥ 30 (85.9%), observed over a 12-month period at our Endocrinology Unit. Treatment cohorts comprised individuals following different regimens: Mediterranean Diet (MD), with an approximate daily intake of 1500 kcal for women and 1800 kcal for men (71% patients); Ketogenic Diet (KD), utilizing the VLCKD protocol characterized by a highly hypocaloric dietary regimen < 800 kcal/day (14% patients); metformin, administered using the oral formulation (5% patients); pharmacological intervention with GLP1-RA administered via subcutaneous injection with incremental dosage (10% patients). Supply constraints limited the efficacy of Liraglutide, whereas Semaglutide was excluded from comparisons due to its unavailability for obesity without diabetes. Blood tests were conducted to assess lipid profile, glycemic profile, and anthropometric parameters, including BMI, waist circumference, and waist-to-height ratio. RESULTS: Significant BMI changes were observed from baseline to 6 months across MD, KD, and Liraglutide groups (p < 0.05). KD exhibited notable reductions in waist circumference and waist-to-height ratio within the initial quarter (p < 0.05), with a significant triglyceride decrease after 6 months (p < 0.05), indicating its efficacy over MD. Liraglutide demonstrated a substantial reduction in HbA1c levels in the first quarter (p < 0.05). During the first three months, the ANOVA test on fasting blood glucose showed a statistically significant impact of the time variable (p < 0.05) rather than the specific treatments themselves (Liraglutide and KD), suggesting that adherence during the early stages of therapy may be more critical than treatment choice. CONCLUSIONS: Positive outcomes from targeted interventions, whether pharmacological or dietary should encourage the exploration of innovative, long-term strategies that include personalized treatment alternation. The absence of standardized protocols underscores the importance of careful and tailored planning in managing obesity as a chronic condition.

Relevance of Behavioral Research in the Evolving State of Anti-obesity Medications: Is the Glass Half Empty or Half Full?

Obesity continues to be a significant public health challenge. While weight loss medications have been studied and available for several years, the newest generation of highly effective anti-obesity medications (AOMs) will shift how behavioral science professionals approach obesity treatment and research. With the unique skill set of behavioral science professionals, this commentary suggests ways to integrate behavioral science into the rapidly evolving landscape of AOM use to accelerate better obesity care and generate new lines of research. The goal of this commentary is to stimulate discussion and encourage responsive and relevant action to improve population health.

A narrative review of approved and emerging anti-obesity medications.

Background: Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping. Objective: This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety. Methods and materials: We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies. Results: Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity. Conclusion: The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.

Obstacles and Opportunities in Managing Coexisting Obesity and CKD: Report of a Scientific Workshop Cosponsored by the National Kidney Foundation and The Obesity Society.

The National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.

Medical treatment of weight loss in children and adolescents with obesity.

Obesity remains one of the biggest health problems both in adults and children. Lifestyle modification, including diet and exercise, continues to be the mainstay of obesity prevention and treatment. Unfortunately, lifestyle modifications are often unsuccessful. Pharmacological treatment of obesity in pediatric patients can be applied in selected cases, and not before evidence of failure of the multidisciplinary lifestyle intervention. In this narrative review, we revised the most up-to-date evidence on medical treatment of weight loss in children and adolescents with obesity, including FDA- or EMA-approved and -experimented, not approved, drugs for pediatric population. Multidisciplinary treatment of childhood obesity, regulation of appetite control, energy balance and body weight were also discussed, in order to clarify the indications and mechanism action of drugs. Despite a substantial number of medications used for the treatment of obesity in adults, a limited number of drugs are approved by the drug regulatory agencies for pediatric population. Further research is needed to evaluate the efficacy and safety of novel pharmacological approaches for treatment of pediatric obesity in order to optimize weight management for children and adolescents and limit the development obesity-related comorbidities.

Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity.

AIMS: Adults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight. DATA SYNTHESIS: A Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (ß = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46-12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12-9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02-14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17-2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15-1.64). CONCLUSIONS: Although we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications. REGISTRATION NUMBER (PROSPERO): CRD42020210329.

Evaluation of an online cognitive behavioural therapy weight loss programme as an adjunct to anti-obesity medications and lifestyle interventions.

BACKGROUND AND OBJECTIVES: Obesity is a global pandemic with psychological, physical and metabolic consequences including in people with mental health conditions. Anti-obesity medications (AOMs) are available to treat obesity and can produce clinically meaningful weight loss but do not address associated psychological issues. We evaluated the usefulness and acceptability of an adjunct online cognitive behavioural therapy (CBT) programme for improving psychological outcomes. METHOD: We conducted a real-world 26-week observational study of 120 adults attending an obesity clinic who undertook a comprehensive weight management programme that included standard diet and exercise interventions, an AOM and an online 10-module CBT intervention. Baseline and 26-week psychological, metabolic and physical measures were compared. RESULTS: At 26 weeks, depression, anxiety, stress and emotional eating levels for the sample decreased significantly compared to baseline (all p < .01). Satisfaction and acceptability were highly rated. The mean weight loss was 8.13 ± 3.83%. Mean waist circumference reduction was 7.62 ± 3.4 cm. DISCUSSION: Online CBT has the potential to be a useful adjunct to AOMs and lifestyle interventions for providing psychological support as shown by improvement in mental health, emotional eating and acceptability scales. This warrants further investigation through a randomised controlled trail.

Weight Management in Patients with Type 1 Diabetes and Obesity.

PURPOSE OF REVIEW: Patients with type 1 diabetes (T1D) are typically viewed as lean individuals. However, recent reports showed that their obesity rate surpassed that of the general population. Patients with T1D who show clinical signs of type 2 diabetes such as obesity and insulin resistance are considered to have "double diabetes." This review explains the mechanisms of weight gain in patients with T1D and how to manage it. RECENT FINDINGS: Weight management in T1D can be successfully achieved in real-world clinical practice. Nutrition therapy includes reducing energy intake and providing a structured nutrition plan that is lower in carbohydrates and glycemic index and higher in fiber and lean protein. The exercise plan should include combination stretching as well as aerobic and resistance exercises to maintain muscle mass. Dynamic adjustment of insulin doses is necessary during weight management. Addition of anti-obesity medications may be considered. If medical weight reduction is not achieved, bariatric surgery may also be considered.

Clinician's Guide for Pediatric Anti-obesity Medications.

The recent advent of highly effective anti-obesity medications (AOM) provides pediatric clinicians a powerful tool to augment the treatment of obesity and improve outcomes. The 2023 American Academy of Pediatrics guidelines state clinicians "should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment". This article will provide an update on the integration of AOM into practice, emphasizing clinical pearls and practical tips.

Patients experience with preoperative use of anti-obesity medications and associations with bariatric surgery expectations.

BACKGROUND: Few studies have investigated the use of anti-obesity medications (AOMs) before bariatric surgery and how prior use impacts patients' goals and expectations for surgery. OBJECTIVES: This study investigated associations between patients' experiences with AOMs and weight loss expectations before bariatric surgery. SETTINGS: Single tertiary university hospital. METHODS: Patients were electronically surveyed with a 31-item questionnaire via email or the patient portal with a primary predictor variable of AOMs presurgery. Outcomes included degree of weight loss and weight regain and motivation for seeking surgery. RESULTS: A total of 346 persons were invited to complete the survey; 112 surveys (32.4%) were completed, with 7 excluded because of not answering the AOM question. 73% reported AOM use. Among those who took AOMs before seeking bariatric surgery, average weight loss was 13 kg (SD 10) corresponding to a 4.4-kg/m2 decrease in BMI. Of past AOM recipients, 87% reported weight regain on stopping AOMs. Average weight regain was 18 kg (SD 13; 126% increase). Patients reported improved longevity and quality of life as motivation for seeking surgery, with AOM use history having no effect. Subjects reported an average weight loss goal of 65.8 kg (39% of baseline weight) from bariatric surgery. CONCLUSIONS: AOMs were commonly used in those seeking bariatric surgery, but motivation for surgery did not differ by AOM use history. Motivations were most often related to goals for better overall health.

Adiposity in Chinese people with type 1 diabetes.

Adiposity, synonymous with obesity, is prevalent among both children and adults with type 1 diabetes in China. Recent literature underscored the patho-physiological and socioeconomic factors associated with adiposity, and consistently highlighted its impact on cardiovascular, kidney, and metabolic diseases among Chinese individuals with type 1 diabetes. Addressing and managing adiposity in individuals with type 1 diabetes are complicated and entail comprehensive approaches including lifestyle modifications, cognitive-behavioral therapy, insulin dose titration, and other diabetes treatment medications. The condition calls for coordination among policymakers, researchers, clinicians, and patients.

Attitudes, weight stigma and misperceptions of weight loss strategies among patients living with obesity in the Lazio Region, Italy.

Introduction: Patient engagement is essential to achieve long-term goals in obesity management. It is crucial to identify patients' perspectives, misperceptions and unmet educational needs on obesity etiology and treatments, to establish a correct therapeutic alliance between healthcare providers and patients. Methods: Objective: This study, promoted by the regional section of the Italian Obesity Society (SIO Lazio), explores attitudes towards obesity, self-awareness, misperceptions of weight loss strategies, experiences of weight stigma and educational needs of patients living with overweight or obesity. Design and subject: We conducted an anonymous survey among patients who accessed an Obesity Management Centers across the Lazio region of Italy for the first time, from October 2023 to April 2024. Approach: The survey consisted of 27 closed-ended questions grouped into 4 sections: (1) sociodemographic factors and self-reported anthropometric measures; (2) self-awareness and attitudes towards obesity and weight loss strategies; (3) experiences of obesity-related stigma; (4) knowledge and perceptions of obesity treatment options. Results: A total of 300 patients (67.9% women, aged 49.1 ± 14.4 years) returned completed surveys. Despite the self-reported BMI 35.3 ± 7.0 kg/m2 with three out of four (75.3%) of participants having a BMI ≥ 30 kg/m2, only 49% correctly identified themselves as affected by obesity. Almost one-third of the patients believed that obesity does not imply a genetic predisposition (31.9%) and that it is always secondary to psychological or behavioral disorders (29.7%). Interestingly, 66.7% of the patients declared themselves as completely responsible for their own condition and 39.4% considered obesity always treatable by means of lifestyle interventions. Stigma and weight discrimination in healthcare settings were reported by a substantial portion of patients (31.9%). A perception of inadequate support from the National Healthcare System emerged in most of the interviews (61.9%). Most patients (72.1%) felt they were not sufficiently informed about anti-obesity medications and a relevant part of their knowledge was derived from healthcare providers (57.7%) and social networks (19.1%). Weight loss medications were considered useful (63.2%) or necessary (18.4%) by the majority of patients, but only 60.1% would accept without any hesitation a pharmacologic treatment. The main reasons for refusal of pharmacological treatments were the belief that lifestyle intervention is a sufficient treatment (46.9%), the fear of adverse effects (28.1%) and feeling defeated (12.5%). Similarly, for most of participants bariatric surgery is useful (73.3%) or necessary (13.6%). Conclusion: Despite advancements in obesity research, this study underscores the need to improve patient education and public awareness to optimize the management and treatment of obesity. Addressing misconceptions, stigma, and gaps in knowledge are critical steps towards improving patient outcomes and fostering a supportive healthcare environment.

Phenotyping of Obesity Treatment Candidates: A Narrative Review.

PURPOSE OF REVIEW: This review explores characterizing candidates for obesity treatments including pharmacotherapy, endoscopic bariatric therapies, and metabolic bariatric surgery (MBS), focusing on established clinical parameters for diagnosing obesity beyond body mass index alone. RECENT FINDINGS: Existing literature primarily provides rates for fat mass percentage (i.e., a marker for adiposity quantity), waist circumference (i.e., a marker for adiposity distribution), and C-reactive protein levels (i.e., a marker for adiposity functionality) among obesity treatment candidates. Limited data on abnormal values and sex-based differentiation exist. The literature indicates high central-tendency measures for fat mass percentage and waist circumference, while C-reactive protein levels vary. Data on the Edmonton Obesity Staging System (i.e., a marker for adiposity-related disease severity) is predominantly available for MBS candidates. Future studies in obesity interventions should improve screening and diagnosis of obesity by incorporating sex-specific considerations and providing abnormal value rates for measurements to enhance understanding of patients' characteristics.

Key messages on obesity care from the 2023 ASPEN Physician Preconference Course: A narrative review.

Obesity is a challenging chronic disease process that continues to affect a large percentage of the population at large. With the advent of new therapeutic options and interventions and a deeper scientific understanding of obesity as a complex illness, there is hope in curtailing this evolving pandemic. In this article, we present key medical information to engage and empower nutrition-focused providers to manage obesity and its nutrition complications. The topics summarized here were presented during the 2023 American Society for Parenteral and Enteral Nutrition Preconference Physician Course and include pathophysiology and hormonal regulation of obesity, multidisciplinary care planning and nutrition risk stratification of patients, and common approaches to treatment, including lifestyle modifications, antiobesity medications, and procedures from the perspective of the nutrition specialist.

A review on drug repurposing applicable to obesity.

Obesity is a major public health concern and burden on individuals and healthcare systems. Due to the challenges and limitations of lifestyle adjustments, it is advisable to consider pharmacological treatment for people affected by obesity. However, the side effects and limited efficacy of available drugs make the obesity drug market far from sufficient. Drug repurposing involves identifying new applications for existing drugs and offers some advantages over traditional drug development approaches including lower costs and shorter development timelines. This review aims to provide an overview of drug repurposing for anti-obesity medications, including the rationale for repurposing, the challenges and approaches, and the potential drugs that are being investigated for repurposing. Through advanced computational techniques, researchers can unlock the potential of repurposed drugs to tackle the global obesity epidemic. Further research, clinical trials, and collaborative efforts are essential to fully explore and leverage the potential of drug repurposing in the fight against obesity.

An overview of therapeutic options of obesity management in India: the Integrated Diabetes and Endocrinology Academy (IDEA) 2023 Congress update.

INTRODUCTION: With newer anti-obesity medications (AOMs) being introduced at a rapid pace, it is prudent to make a concise and updated clinical practice document that may help busy clinicians in daily clinical practice. A group of metabolic physicians, diabetologists, endocrinologists, and bariatric surgeons assembled during the Integrated Diabetes and Endocrine Academy 2023 Congress (IDEACON, July 2023, Kolkata, India) to compile an update of pharmacotherapeutic options for managing people with obesity in India. AREAS COVERED: After an extensive review of the literature by experts in different domains, this update provides all available information on the management of obesity, with a special emphasis on both currently available and soon-to-be-available AOMs, in people with obesity. EXPERT OPINION: Several newer AOMs have been shown to reduce body weight significantly, thus poised to make a paradigm shift in the management of obesity. While the tolerability and key adverse events associated with these AOMs appear to be acceptable in randomized controlled trials, pharmacovigilance is vital in real-world settings, given the absence of sufficiently long-term studies. The easy availability and affordability of these drugs is another area of concern, especially in developing countries like India.

Stratified analysis of the association between anti-obesity medications and digestive adverse events: a real-world study based on the FDA adverse event reporting system database.

BACKGROUND: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs. METHODS: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis. RESULTS: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42-3.6). Orlistat (ROR = 3.30, 95% CI: 3.08-3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45-10.88) with phentermine-topiramate still needs further clarification. CONCLUSIONS: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events.

Special considerations for the adolescent with obesity: An obesity medicine association (OMA) clinical practice statement (CPS) 2024.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details special considerations for the management of the adolescent with obesity. The information in this CPS is based on scientific evidence, supported by medical literature, and derived from the clinical experiences of members of the OMA. Methods: The scientific information and clinical guidance in this CPS are based on scientific evidence, supported by the medical literature, and derived from the clinical perspectives of the authors. Results: This OMA Clinical Practice Statement addresses special considerations in the management and treatment of adolescents with overweight and obesity. Conclusions: This OMA Clinical Practice Statement on the adolescent with obesity is an overview of current recommendations. These recommendations provide a roadmap to the improvement of the health of adolescents with obesity, especially those with metabolic, physiological, and psychological complications. This CPS also addresses treatment recommendations and is designed to help the provider with clinical decision making.