Anti-obesity Research Articles

Costs of treating serious adverse effects of drugs used for treatment of obesity: comparison of selected European countries

Drugs for the treatment of obesity show significant effectiveness, but the adverse effects (ADRs) of these drugs are numerous and varied, and some of them are highly cost-generating. Our research aimed to define the health care utilization pattern in treating ADRs of antiobesity therapy, to compare the costs of treating these ADRs among selected European countries, and to identify the key cost drivers. A comparative analysis of the costs of treating the ADRs of antiobesity drugs in 10 European countries (seven EU members and three from the Western Balkans) was conducted, and the impact of parameters of global health expenditures on them was assessed. There are considerable differences in costs of treating adverse antiobesity drug reactions among European countries: costs of treating gastroesophageal reflux disease varied almost 20 times between North Macedonia (12.6 EUR) and Estonia (202.9 EUR). The Gross Domestic Product per capita was an important cost driver in treating the majority of the ADRs studied (p < .001), except for retinopathy, anaphylaxis, and respiratory disorders. The Domestic Private Health Expenditure increased the costs of treating depression (p = .012), upper respiratory tract infection (p = .008), melanocytic naevus (p = .027), and drug-induced hepatitis (p = .023). Investment in pharmaceuticals, medical goods, and preventive care tended to reduce the costs of treating several ADRs, which are seemingly unrelated to the body site or mechanism. Healthcare utilization and costs of treating ADRs to antiobesity drugs vary significantly among European countries. These differences should be considered when creating inputs for cost-effectiveness and budget impact models to decrease their uncertainty.

Self-awareness Regarding Obesity and Specific Therapy in Patients with Overweight or Obesity and Cardiovascular Diseases from Moscow Region

Objective: Despite the proven effectiveness of lifestyle interventions and specific medications in the treatment of obesity, little is known about their use in real-world practice. . Aims: To study the awareness of patients about the problem of overweight/obesity, as well as the clinical practice of non-drug and drug therapy according to the survey Material and Methods: Eligible patients were recruited from the prospective outpatient registry of patients with cardiovascular diseases. The design of the study was a cross-sectional cohort singlecentre. All of the included patients completed a specifically designed questionnaire. The study included 295 patients (mean age 66.8 ± 11.8 years) with a body mass index (BMI) of ≥ 25 kg/m2. One hundred eight (36.6%) individuals were overweight, 124 (42.2%) had first-class obesity, 42 (14.2%) had second-class obesity, and 21 (7.1%) patients had third-class obesity. Results: 252 patients (85.4%) were informed of being overweight/obese, and all of them received non-drug recommendations for the treatment of obesity. Anti-obesity medications (AOM) were recommended only to 25 (8.5%) patients: 3 – overweight, 11 – obesity class I, 6 obesity class II, and 5 – obesity class III. Twenty-one (7.1%) patients took the prescribed medications (84% adherence). The drugs were more often taken by patients with class II and III disease (40.5% and 57.1% of patients, respectively). Overweight (8.5%) and class I obesity (18.0%) patients took these drugs less often (p &lt; 0.0001). Conclusion: The results of the survey have demonstrated good awareness of patients about their obesity/overweight and quite frequent use of non-drug obesity therapy. However, the rate of AOM prescription was extremely low.

Transforming the diabetes outcomes for people with mental illness

AbstractThere is a complex bidirectional relationship between diabetes and mental illness, where diabetes is associated with an increased prevalence of a range of mental disorders and several mental illnesses increase the risk of diabetes. The reasons why people with mental illness are at higher risk of diabetes and vice versa are multifactorial. When diabetes and mental illness occur together, the outcomes for both conditions are worsened, and the co‐morbidity places a higher burden on the individual living with the conditions.Severe mental illness is associated with a twofold increased risk of diabetes, and the onset of diabetes is approximately 10 years earlier in people with mental illness than in the general population. Health behaviour interventions to reduce the incidence of diabetes may be less effective than previously thought. However, trials on obesity drugs, particularly glucagon‐like peptide‐1 receptor agonists, are showing promise. Diabetes care for people with severe mental illness seems to have improved in the past decade. Interventions have been developed to address the unique challenges of living with severe mental illness and diabetes.Depression is twice as common in people with diabetes. Depression increases the risk of diabetes and vice versa. Although general population risk factors for depression apply to people with diabetes, diabetes‐specific risk factors include the development of complications and insulin use in people with type 2 diabetes. Managing depression includes efforts to prevent depression, timely diagnosis and treatment with psychological or pharmacological treatments.Health care professionals have a responsibility to ensure that people with mental illness and diabetes are not disadvantaged.

Effective but inaccessible antiobesity medications: A call for sharing responsibility for improving access to evidence-based care.

Effective but inaccessible antiobesity medications: A call for sharing responsibility for improving access to evidence-based care.

Twelve-month analysis of real-world evidence from a telehealth obesity-treatment provider using antiobesity medications.

The objective of this study was to describe weight changes in members of a large-scale telehealth obesity-treatment provider who were using antiobesity medications (AOMs). This retrospective observational study analyzed real-world data from adults who initiated AOM treatment with the WW International, Inc. (formerly Weight Watchers) Clinic telehealth program between January 2022 and July 2023 (n = 53,590). The main outcomes were changes in body weight over 12 months, side effects over follow-up, and medication usage patterns. The 53,590 patients who initiated treatment were predominantly female (88.6%), with a mean BMI of 36.9 kg/m2. Mean (SD) treatment duration was 5.3 (4.3) months. Program retention rates based on the number of patients whose time from enrollment was at least 3, 6, 9, and 12 months were 78% (n = 39,907/51,247), 63% (n = 25,515/40,203), 58% (n = 15,472/26,794), and 77% (n = 6459/8394), respectively. Average weight loss was 8.9% at 3 months (n = 37,565), 14.1% at 6 months (n = 24,140), 17.7% at 9 months (n = 15,169), and 19.4% at 12 months (n = 6089). Glucagon-like peptide-1 receptor agonist (GLP-1-RA)-based treatments were predominant. Side effects were consistent with the classes of medications used, and frequency declined over time. This real-world analysis of a telehealth-delivered obesity-treatment program demonstrated outcomes consistent with recent phase 3 clinical trials of AOMs, suggesting generalizability beyond clinical trial and in-person settings.

The Phytochemistry and Medicinal value of Psidium guajava ( guava ) : Antiobesity Effect

Obesity in society has reached epidemic proportions in the 21 st century. Being Overweight is not only appearance issue but also is actually a medical concern, because it is serious health condition. Diabetes and Heart diseases that can stem from obesity . The plant Psidium guajava Linn (Guava) is used not only as food but also as folk medicine. We subjected the leaves of these plant for Alcoholic extraction using solvent Ethanol and extract were prepared we infer that the oral administration of guava leaves extract shows Anti Obesity effect (weight loss). So this study proves that the guava leaves extract helps to control obesity.

Anti-obesity treatment preferences of healthcare providers and people living with obesity: A survey-based study.

A cross-sectional, online survey was conducted in the United Kingdom, France, Germany, and the United States (14 November-22 December 2022) to investigate preferences for anti-obesity medication (AOM) among people with obesity (PwO) and healthcare providers (HCPs). Eligibility: Adult PwO who self-defined their body type as overweight/obese, were trying to lose weight and had BMI ≥30.0 or 27.0-29.9 kg/m2 with ≥1 obesity-related complication; HCPs had to see ≥30 PwO in a typical month and be a decision-maker regarding their weight loss. The survey included 2500 PwO and 500 HCPs. Exercise (96%) and diet (90%) were the most common weight management methods; AOM use was low (8%). Key barriers to use of prescribed AOMs among PwO were not wanting to take AOM (34%), side effects concerns (33%), and not trusting AOM (26%). Most HCPs (79%) had prescribed/recommended AOMs. Efficacy was the most common reason for preferring one of the shown product profiles among PwO (60%) and HCPs (86%); improving cardiovascular risk was also important to 95% of HCPs when deciding which AOM to prescribe. AOM preference is largely driven by efficacy. Increasing knowledge could help to address barriers to AOM use and improve outcomes for PwO.

Cardiometabolic outcomes in patients with overweight and obesity undergoing weight loss trials : a network meta-analysis

Abstract Objective Cardiometabolic outcomes are intrinsically linked with obesity. According to a study by Jayedi A et al. a 5kg weight gain could increase CVD mortality and MI risk by 11% and 18% respectively, with most overweight and obese patient also suffering from cardiometabolic derangements. This network meta-analysis evaluates cardiometabolic effects bought about by glucagon-like peptide 1 receptor agonists (GLP-1 RA) and other weight loss drugs in an overweight and obese population. Methods Cochrane CENTRAL, Embase and Medline were searched for randomised clinical trials (RCTs) on GLP-1 RA and United States Food and Drug administration weight loss drugs. A network meta-analysis was performed, using risk ratios(RR) to compare the efficacy of the interventions against one another. Network diagrams and surface under the cumulative ranking curve analysis were generated for the following cardiometabolic outcomes ( LDL, HDL, TC, TG, HbA1c, FPG, SBP and DBP). Results Among the cardiometabolic outcomes analysed, the GLP-1RA’s consistently ranked on top, with tirzepatide followed by semaglutide and then liraglutide. In terms of glycaemic control, tirzepatide 15, 10 and 5mg ranked first in a dose dependent manner(SUCRA = 0.8480, 0.8410, 0.6725) followed by semaglutide1.7mg(SUCRA= 0.6232). Tirzepatide 15mg did not achieve statistical significance compared to semaglutide 1.0mg (MD: -0.77, 95%CI: -2.04 to 0.50) or liraglutide1.8mg (MD: -0.64, 95%CI: -1.68 to 0.41). In reducing blood pressure, tirzepatide exhibiting a dose dependent reduction with Tirzepatide 15mg, (SUCRA =0.9457),10mg(SUCRA=0.9069)and 5mg(SUCRA=0.8419) followed by semaglutide 1.7mg (SUCRA =0.7415) then liraglutide 1.8mg(SUCRA = 0.5521).Tirzepatide 15mg demonstrated statistical significance compared to semaglutide 1.0mg (MD: -3.53, 95%CI: -6.78 to -0.27) and liraglutide 3.0mg (MD: -3.47, 95%CI: -5.59 to -1.36). The GLP-1RA’s also exhibited superiority in lipid reduction for TC and TG, with tirzepatide reducing TC (SUCRA = 0.7867) and TG(SUCRA = 0.9843) followed by semaglutide 1.7 mg (SUCRA = 0.7796) for TC and tirzepatide 10 mg (SUCRA = 0.9018) for TG. Orlistat 120mg(SUCRA =0.8789) and 60mg(SUCRA= 0.8458) were superior in reducing LDL, with tirzepatide 15mg(SUCRA =0.7806) and then semaglutide 2.4mg(SUCRA=0.7260) coming in behind. Naltrexone 32mg/Bupropion 360mg(SUCRA = 0.8757) ranked first followed by tirzepatide(SUCRA=0.8593) in increasing HDL, however the increase was not statistically significant (MD: 0.00, 95%CI: -0.04 to 0.05). Conclusion GLP-1 RAs’ superiority in addressing cardiometabolic parameters that are often deranged in patients with overweight and obesity highlights the need for weight lost medication transitioning from one that decreases and suppresses appetite or prevent the absorption of lipids to one that targets the altered metabolic mileu of patients with overweight and obesity, highlighting the multipronged approach needed to treat this metabolic disease.

A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis

Abstract Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

Effects of body mass index on worsening of heart failure and all-cause death in patients with heart failure and reduced left ventricular ejection fraction: a 10-year follow-up study

Abstract Background/Introduction Obesity in patients with heart failure (HF) with reduced ejection fraction (HFrEF) is common, and with the emergence of effective anti-obesity drugs, a better understanding of the relation between BMI and clinical outcome in HFrEF is needed. Purpose This study aimed to analyse whether a body mass index (BMI) above 27 kg/m2 (cut-off used in trials) is associated with a greater rate of all-cause death and HF hospitalization in patients with HFrEF. Methods We included 1,017 medically optimized according to existing HF guidelines at the time and clinically stable HF patients with a left ventricular ejection fraction of &amp;lt;45% from the NorthStar study. Patients were included between 2005 and 2009 and followed for 10 years using Danish nationwide registries. The outcomes of interest were all-cause death and hospital discharge for HF (overnight stay). Descriptive statistics were grouped according to tertiles of BMI. The association between BMI as a continuous variable and the outcomes of interest was analysed using restricted cubic splines in Cox proportional-hazards models. Reported were hazard ratios (HR) with 95% confidence intervals (CI) adjusted for relevant prognostic covariates (reference: BMI = 27 kg/m2). Results At enrolment, the median age was 69 years, 75% were men, and the median BMI was 26.3 kg/m2 (Table 1). Patients in the upper 3rd BMI tertile were younger (median age 67), had a lower level of NT-proBNP level (median 737.5 pg/ml) and a higher proportion of diabetes (29.9%). During 10 years of follow-up, HF hospitalization occurred in 683 patients (61.7%), and 623 patients died (56.3%). A BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization (significantly from BMI 35.2 kg/m2: HR 1.30 [CI 1.00-1.68]; Figure 1). Similar findings were observed for all-cause mortality (significantly from BMI 35.7 kg/m2: HR 1.27 [CI 1.00-1.62]) Conclusion In patients with HFrEF, a BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization and all-cause death. Efforts to find effective and safe approaches to reducing weight in obese patients with HFrEF are warranted.Figure 1

Morus alba: natural and valuable effects in weight loss management

Overweight and obesity are conditions associated with serious comorbidities, such as diabetes and cardiovascular disease. Prevalence of excessive fat accumulation is increasing worldwide, and thus the need for efficient and sustainable weight loss regimes has become a major issue in clinical practice. Despite the important advances in the development of anti-obesity medications (AOM), their side effects, cost, and accessibility, are limiting factors for their routine use. Conversely, the studies of medicinal plants for weight management holds strong promise as a growing area of research. This review consolidates the representative evidence about the beneficial impacts of Morus alba on weight management and associated metabolic parameters, encompassing: inhibition of digestive enzymes, and thus contribution to the energy deficit required for weight loss, improvements in glucose and lipid metabolism, and attenuation of adiposity. Findings from in vitro, in vivo, and clinical investigations reviewed in the paper, demonstrate that white mulberry extracts have the potency to supplement efficiently and safely a healthy weight management approach.

Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice

Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005’s anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically.

Nanomaterial-Enhanced Microneedles: Emerging Therapies for Diabetes and Obesity.

Drug delivery systems (DDS) have improved therapeutic agent administration by enhancing efficacy and patient compliance while minimizing side effects. They enable targeted delivery, controlled release, and improved bioavailability. Transdermal drug delivery systems (TDDS) offer non-invasive medication administration and have evolved to include methods such as chemical enhancers, iontophoresis, microneedles (MN), and nanocarriers. MN technology provides innovative solutions for chronic metabolic diseases like diabetes and obesity using various MN types. For diabetes management, MNs enable continuous glucose monitoring, diabetic wound healing, and painless insulin delivery. For obesity treatment, MNs provide sustained transdermal delivery of anti-obesity drugs or nanoparticles (NPs). Hybrid systems integrating wearable sensors and smart materials enhance treatment effectiveness and patient management. Nanotechnology has advanced drug delivery by integrating nano-scaled materials like liposomes and polymeric NPs with MNs. In diabetes management, glucose-responsive NPs facilitate smart insulin delivery. At the same time, lipid nanocarriers in dissolving MNs enable extended release for obesity treatment, enhancing drug stability and absorption for improved metabolic disorder therapies. DDS for obesity and diabetes are advancing toward personalized treatments using smart MN enhanced with nanomaterials. These innovative approaches can enhance patient outcomes through precise drug administration and real-time monitoring. However, widespread implementation faces challenges in ensuring biocompatibility, improving technologies, scaling production, and obtaining regulatory approval. This review will present recent advances in developing and applying nanomaterial-enhanced MNs for diabetes and obesity management while also discussing the challenges, limitations, and future perspectives of these innovative DDS.

The Association between a Recorded Diagnosis of Obesity and Clinically Significant Weight Loss in the Primary Care Setting: A Nationwide Registry.

Overweight and obesity (OW/OB) are underdiagnosed. The primary aim was to assess whether a diagnosis of OW/OB recorded by a primary care physician (PCP) is associated with clinically significant weight loss, compared to a missed diagnosis. The secondary aim was to investigate the association between OW/OB diagnosis and patient attendance at dietary consultations. This retrospective, observational cohort study was conducted using a nationwide healthcare database. The study included a random sample of 200 000 adults with BMI ≥ 25 kg/m2, recorded on a primary care visit, between 2014-2020. Patients with prior diagnosis of OW/OB or obesity-related complications were excluded. The independent variable was OW/OB diagnosis recorded by the PCP immediately after BMI measurement. The outcome variable was ≥5% weight loss at a second weight measurement within 9-15 months. Multivariate regression analysis was applied. Of the 200 00 people with OW/OB, 36 033 (18.0%) had a diagnosis of OW/OB, and 37 368 (18.7%) had a second body weight measurement, of which 7 635 (20.4%) lost ≥5% of their baseline body weight. The prescription rate of anti-obesity medication was 1.2% and did not differ between patients who achieved weight loss and those who did not. Those with a recorded diagnosis were 2.6 times more likely to visit a dietitian (OR 2.57, 95%CI 2.56-2.64) and 2.5 times more likely to achieve weight loss (OR 2.53, 95%CI 2.46-2.60). After adjusting for multiple confounders, including attendance at dietary consultation, people who received OW/OB diagnosis were 32% more likely to achieve weight loss (OR 1.32 95% CI 1.28-1.36, p&lt;0.001) compared to people with missed diagnosis. Recording a diagnosis of obesity among relatively healthy people is associated with clinically significant weight loss at 1 year follow up, independent of attendance at dietary consultation. Early obesity diagnosis is a significant opportunity to promote weight loss in the primary care setting and may affect weight trajectory.

Can weight-loss drugs tackle the mental health crisis?

Can weight-loss drugs tackle the mental health crisis?

Exploring the therapeutic mechanisms of millet in obesity through molecular docking, pharmacokinetics, and dynamic simulation.

Obesity, a prevalent global health concern, is characterized by excessive fat accumulation, which confers significant nutritional and health risks, including a shortened lifespan and diminished wellbeing. Central to the regulation of energy balance and food intake is the fat mass and obesity-associated (FTO) protein, which modulates the interplay between caloric consumption and energy expenditure. Given its pivotal role in obesity regulation, the identification of effective inhibitors targeting the FTO protein is imperative for developing therapeutic interventions. Currently available anti-obesity drugs are often plagued by undesirable side effects. In contrast, natural plant-derived bioactive compounds are gaining prominence in the pharmaceutical industry due to their efficacy and lower incidence of adverse effects. Little Millet, a traditional cereal known for its rich nutritional profile and high satiety index, was investigated in this study using molecular docking and dynamics simulation approach for its potential as an anti-obesity agent. Our research demonstrates that four bioactive compounds from Little Millet exhibit superior binding energies ranging from 7.22 to 8.83 kcal/mol, compared to the standard anti-obesity drug, orlistat, which has a binding energy of 5.96 kcal/mol. These compounds fulfilled all drug-like criteria, including the Lipinski, Ghose, Veber, Egan, and Muegge rules, and exhibited favorable profiles in terms of distribution, metabolism, and prolonged half-life without toxicity. Conversely, orlistat was associated with hepatotoxicity, a reduced half-life, and multiple violations of drug-likeness parameters, undermining its efficacy. Molecular dynamics simulations and Gibbs free energy assessments revealed that the four identified compounds maintain stable interactions with key residues in the FTO protein's active site. We propose further validation through extensive In vitro, In vivo, and clinical studies to ascertain the therapeutic potential of these compounds in combating obesity.

Simultaneous Overcoming Approach for Poor Wettability and Low Stability in Stomach by Simple Methods; Formulation Design and Development of Monoacylglycerol Acyltransferase 2 Inhibitor, S-309309.

N-[(4R)-5,7-Difluoro-2'-(5-methylpyridin-2-yl)-4'-oxo-2,2',3,4',5',7'-hexahydrospiro[1-benzopyran-4,6'-pyrazolo[4,3-c]pyridin]-3'-yl]-2-(methanesulfonyl)acetamide (S-309309) is an anti-obesity drug developed by Shionogi & Co., Ltd. that has a monoacylglycerol acyltransferase 2 inhibitory effect. S-309309 has poor wettability, and the amount of the degradation product (4R)-3'-amino-5,7-difluoro-2'-(5-methylpyridin-2-yl)-2,2',3,7'-tetrahydrospiro[[1]benzopyran-4,6'-pyrazolo[4,3-c]pyridin]-4'(5'H)-one (compound 8) increases over time under acidic conditions. In this study, we have tried to improve S-309309 wettability and suppress the amount of degradation product increased under acidic conditions. As a result of the study, we found that by mixing with a water-soluble polymer, the wettability of S-309309 and its dissolved concentration in fluid were increased suggesting that its dissolution behavior should be enhanced. In addition, by encapsulating S-309309, the increase of degradation product amount was suppressed under acidic conditions, suggesting that the suppression of degradation product formation would be expected in the stomach after oral dosing. Overall, these results suggest that the drug property issues of S-309309 can be overcome by mixing S-309309 with a water-soluble polymer and encapsulation.

Estimating the lives that could be saved by expanded access to weight-loss drugs

Obesity is a major public health crisis in the United States (US) affecting 42% of the population, exacerbating a spectrum of other diseases and contributing significantly to morbidity and mortality overall. Recent advances in pharmaceutical interventions, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) and dual gastric inhibitory polypeptide and GLP-1 receptor agonists (e.g., tirzepatide), have shown remarkable efficacy in weight-loss. However, limited access to these medications due to high costs and insurance coverage issues restricts their utility in mitigating the obesity epidemic. We quantify the annual mortality burden directly attributable to limited access to these medications in the US. By integrating hazard ratios of mortality across body mass index categories with current obesity prevalence data, combined with healthcare access, willingness to take the medication, and observed adherence to and efficacy of the medications, we estimate the impact of making these medications accessible to all those eligible. Specifically, we project that with expanded access, over 42,000 deaths could be averted annually, including more than 11,000 deaths among people with type 2 diabetes. These findings underscore the urgent need to address barriers to access and highlight the transformative public health impact that could be achieved by expanding access to these novel treatments.

GLP-1 Receptor Agonists and the Path to Sustainable Obesity Care

This Viewpoint discusses the optimal treatment duration of glucagon-like peptide-1 receptor agonists in people with obesity and the benefits of off-ramping, the tapering of these antiobesity medications following an initial treatment period.

Obesity Nephropathy: A Current Overview

The obesity pandemic is a public health problem that is evolving at high speed with both functional and vital outcomes. Recently, many studies have shown that obesity is a driver of chronic kidney disease onset and progression. The mechanisms underlying this fact are multiple including inflammation, oxidative stress, insuline resistance and hemodynamic change with inappropriate RAAS and SNS activation; occuring on a particularly genetic basis of individual predisposition. In this field, Obesity-related glomerulopathy is characterized by glomerulomegaly with localized and segmental glomerulosclerosis lesions. Main symptoms are non specific, dominated by microproteinuria, rarely nephrotic syndrome and a slowed decline in glomerular filtration rate. As for treatment, it starts essentially with lifestyle interventions targeting a meaningful and sustainable weight loss, accompanied by antiobesity medications (AOMS) including RAAS blockers, SGLT2inhibitors and since very recently, long-acting glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) which were shown to be effective in managing weight loss in non-chronic kidney disease (CKD) patients. Preliminary results of more definitive studies in CKD patients are currently being finalized. Bariatric surgery could reduce the risk of mortality in obese CKD patients; it is recommended for patients with severe morbid obesity, poor tolerance to AOMS, particularly GLP RA, or those whose long-term medication costs represent a barrier to sustainable results. In this review, we summarize epidemiological data on obesity nephropathy, its pathophysiological mechanisms, clinical features and perspectives on its treatment.