Anti-obesity Medicines Research Articles

Efficacy and Safety of Novel Twincretin Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, as an Anti-obesity Medicine in Individuals Without Diabetes: A Systematic Review and Meta-analysis.

Aims: To date, no meta-analysis has analyzed the efficacy and safety of tirzepatide as an anti-obesity medication in individuals without diabetes. This meta-analysis was undertaken to address this knowledge gap. Materials and methods: Electronic databases were searched for randomized controlled trials (RCTs) involving individuals with obesity without diabetes receiving tirzepatide in the intervention arm and placebo in the control arm. The primary outcome was the percentage change in weight from baseline, and the secondary outcomes included the change in weight from baseline; a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25%; glycaemic parameters; lipid parameters and adverse events. Results: From 281 initially screened articles, data from 2 RCTs involving 1,852 participants were analyzed. The efficacy and safety of tirzepatide 15 mg (or the highest tolerable dose) versus placebo were analyzed. The percentage change in body weight was higher with tirzepatide than with placebo (mean difference [MD]: -19.44%; 95% confidence interval [CI]: -22.48 to -16.41; p<0.00001). Tirzepatide also had a higher absolute reduction in body weight (MD: -17.55 kg; 95% CI: -32.15 to -2.95; p<0.00001). Higher percentages of people on tirzepatide had a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% compared with placebo. Improvements in glycaemic and cardiometabolic parameters were observed with tirzepatide. Tirzepatide was associated with a higher number of participants with one or more adverse events, which leads to treatment discontinuation, and severe or serious gastrointestinal events. Conclusion: This meta-analysis provides exciting data on the impressive weight loss properties of tirzepatide over 72 weeks of clinical use in individuals with obesity without diabetes.

Obesity pharmacotherapy in older adults: a narrative review of evidence.

The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the 'obesity paradox'. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

Development of Multi-particulate Formulation of Glabridin with L-Phenylalanine and Its Pre-clinical Evaluation for Anti-obesity Activity

Obesity is a chronic condition that is defined by pathophysiological mechanisms that lead to an increase in adipose tissue mass as a result of positive energy balance. Obesity is a multi-factorial disorder involving different mechanisms of action like humoral and neurogenic actions. Hypertrophied and hyperplastic adipocytes are indicative of pathological obesity. In the current treatment regimen, the drugs used mainly focus on a single mechanism of action. Herbal medicines are reported to have anti-obesity activity but due to the presence of multiple phytoconstituents its very difficult for one to finalize the dose and issue of palatability. So the best solution is to focus on usage of active phytoconstituent as an anti-obesity medicine. A high protein diet proved to have anti-obesity activity, the main constituent responsible for this activity is L-phenylalanine which is an essential amino acid that produces its activity by stimulating the satiety centre and thus decreases food intake. In this study, we are combining glabridin from Glycyrrhiza glabra and L-phenylalanine as both show anti-obesity activity through different action mechanisms, which may result in synergism. The study aims to prepare multi-particulate system (granules) of glabridin with L-phenylalanine and evaluate their anti-obesity and hypo-lipidemic action in HFD-treated rats.

Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis.

Orforglipron is a novel once-daily oral non-peptide glucagon-like peptide-1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta-analysis has analyzed the efficacy and safety of orforglipron; this meta-analysis aimed to address this knowledge gap. A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow-up duration of up to 36weeks. Compared to placebo, patients receiving orforglipron 12mg/day (mean difference (MD), MD -5.48%, 95% CI [-7.64, -3.33], p<0.01), 24mg/day (MD -8.51%, 95% confidence interval (CI) [-9.88, -7.14], p<0.01), 36mg/day (MD -8.84%, 95% CI [-11.68, -6.00], p<0.01) and 45mg/day (MD -8.24%, 95% CI [-12.84, -3.63], p<0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p=0.0003), 36mg/day (OR 17.43, 95% CI [3.18, 95.66], p=0.001) and 45mg/day (OR 23.17, 95% CI [4.37, 123.03], p=0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side-effects were predominant side effects, being dose-dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Orforglipron at 24-45mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24-36mg/day is the most optimal dose for orforglipron as an anti-obesity medicine.

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.

Cardiometabolic Risk, Peripheral Arterial Disease and Cardiovascular Events in Polycystic Ovary Syndrome: Time to Implement Systematic Screening and Update the Management.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. It presents with gynaecologic, metabolic, and psychologic manifestations. The dominant drivers of pathophysiology are hyperandrogenism and insulin resistance. Both conditions are related to cardiometabolic risk factors, such as obesity, hypertension, dyslipidaemia, hyperglycaemia, type 2 and gestational diabetes, nonalcoholic fatty liver disease and obstructive sleep apnoea. Women with PCOS of reproductive age consistently demonstrated an elevated risk of subclinical atherosclerosis, as indicated by different measurement methods, while findings for menopausal age groups exhibited mixed results. Translation of subclinical atherosclerosis into the increased incidence of peripheral arterial disease and major cardiovascular (CV) events is less clear. Although several expert groups have advised screening, the CV risk assessment and prevention of CV events are frequently underdiagnosed and overlooked aspects of the management of PCOS. A combination of lifestyle management and pharmacotherapy, including the promising new era of anti-obesity medicine, can lead to improvements in cardiometabolic health.

Diet-induced animal model anti-obesity, phytochemical profiling, and in silico analysis of culinary plant gokhru (Pedalium murex L.) mucilage

Plant-based diets (PBDs) are renowned for managing and developing bioactive chemical inhibitors to combat obesity, a well-known global public health concern. There are currently no published research studies examining the effects of food plant mucilage dietary supplements on animal models of obesity induced by high-fat diets (HFD). The present research investigated the anti-obesity properties of the culinary plant Pedalium murex L. mucilage (PMM) in obese albino male rats models fed HFD. PMM's HR-LCMS phytochemical profiling and in silico evaluation of anti-obesity and drug-likeness using Schrodinger’s Glide, QikProp, and GROMACS modules were also investigated. In vivo, anti-obesity model animal rat’s daily dietary intake, common blood biochemical parameters, and histological examination of the liver and kidney tissues for the development of macrovesicular and microvesicular steatosis were all performed. Among the 46 Phytochemicals profiled, 7(14)-Bisabolene-2, 3, 10,11tetrol, Moschamine, and N-Feruloyltyramine show prominent anti-obesity activity and drug-like characteristics in silico. Rats given PMM showed significantly lower serum levels of total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TGs), increased levels of high-density lipoprotein (HDL), as well as macro-and microvesicular steatosis, lobular inflammation of the liver and kidney tissues. This suggests that PMM is an effective natural anti-obesity therapeutic ingredient or dietary supplement with a high concentration of anti-obesity phytochemicals that mainly satisfies the needs for such natural anti-obesity medicine or a supplement. Communicated by Ramaswamy H. Sarma

Potential anti-obesity/inflammatory flavonoid-derived biomolecules against Obesity to prevent WAT differentiation by targeting a DNA-binding protein inhibitor, ID-1.

A concoction of unhealthy eating, inactivity, and the adverse effects of specific drugs brings on obesity. The primary cause of Obesity is the storage of too much energy and triglycerides in adipocytes, particularly white adipose tissue (WAT). In addition to modifying one's lifestyle, anti-obesity medicines are increasingly used as adjuvant therapy. Flavonoids are the major class of compounds having significant biological impacts and health-improving properties. To find novel flavonoid compounds that fight obesity using computational drug design techniques. This work targets 1DI protein to predict new flavonoid compounds that fight obesity. The study uses computational approaches to anticipate potential anti-obesity/inflammatory flavonoid compounds against obesity to prevent WAT differentiation by targeting ID-1, a DNA-binding protein inhibitor. Our study led to the identification of the protein target inhibitor lead CID: 5280443, which was found to be a potent inhibitor of the receptor. According to the findings of this study, this bio-active molecule may be used as a lead for the development of drugs that preferentially fight obesity without interfering with the functions of the human proteasome. The scientific community will benefit from these discoveries, which could aid in the creation of new medications that treat obesity more successfully.

Tirzepatide - A major breakthrough in the fight against obesity.

Madam, inflating numbers of sufferers of Type 2 Diabetes and obesity have led scientists to coin the term ‘diabesity,’ which signifies a pathogenic link between obesity and diabetes. Obesity, defined as a BMI of at least 30 kg/m2,1 is a complex, chronic, relapsing illness characterized by an excessive fat build-up. According to the World Obesity Atlas, one billion people will be obese (BMI 30kg/m2) by 2030.2 Obesity is not an illness. Still it is a substantial risk factor for cardiovascular disease and Type 2 diabetes, which are major morbid disease burdens.1 Obesity has genetic, biological, psychological, social, economic, and environmental bases. A complex network of neurohormonal, physiological, and behavioural systems that regulate body weight, combined with different risk factors that impair weight loss pathways, renders lifestyle therapy ineffective in managing obesity. Several clinical guidelines now promote anti-obesity treatments for successful management and considerable outcomes.3 Considering a recent study published on June 4th from a phase three Randomized Control Trial conducted in nine countries, Tirzepatide, originally used to treat diabetes, showed efficacy and safety as an anti-obesity medicine in 2539 non-diabetic patients. When combined with Glucose-dependent Insulinotropic polypeptide and Glucagon-Like Peptide-1 Receptor Agonist, weight-loss efficacy increased. The trial assigned individuals to receive Tirzepatide or placebo subcutaneously once weekly for 72 weeks. In the SURMOUNT-1 research, subjects on 5mg, 10mg, and 15mg lost 35.5lbs, 48.9lbs, and 52lbs, respectively, compared to 5.3lbs on placebo. Compared to the 35% of placebo-takers who dropped 5% or more weight, those taking the medication at 5mg, 10mg, and 15mg lost 85%, 89%, and 91%. In the intervention group, waist circumference, blood pressure, insulin, cholesterol, and aspartate aminotransferase also improved. No direct trial has compared Tirzepatide to Semaglutide or bariatric surgery, but the findings imply it's more effective than the current anti-obesity therapies. However, mild to moderate gastrointestinal side effects do happen.4 By 2030, Pakistan's obesity pandemic will have reached a peak of 12.9%.2 This, coupled with the fact that we have the highest Diabetes rate in South Asia,5 makes these findings a huge milestone since Tirzepatide can act simultaneously as an anti-diabetic and anti-obesity drug. However, because the drug must be prescribed for an extended period, more testing is required before it can be made available to the public. The cost must also be considered to ensure affordability. Nonetheless, the study's findings are encouraging and may lead to novel obesity and diabetes care methods.

Pharmacological Treatments and Natural Biocompounds in Weight Management.

The obesity pandemic is one of society's most urgent public health concerns. One-third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming years. Generally, the treatment strategy for obese patients is largely patient-centric and needs dietary, behavioral, pharmacological, and sometimes even surgical interventions. Given that obesity cases are rising in adults and children and lifestyle modifications have failed to produce the desired results, the need for medical therapy adjunct to lifestyle modifications is vital for better managing obesity. Most existing or past drugs for obesity treatment target satiety or monoamine pathways and induce a feeling of fullness in patients, while drugs such as orlistat are targeted against intestinal lipases. However, many medications targeted against neurotransmitters showed adverse events in patients, thus being withdrawn from the market. Alternatively, the combination of some drugs has been successfully tested in obesity management. However, the demand for novel, safer, and more efficacious pharmaceutical medicines for weight management does exist. The present review elucidates the current understanding of the available anti-obesity medicines of synthetic and natural origin, their main mechanisms of action, and the shortcomings associated with current weight management drugs.

Medicines for Obesity: Appraisal of Clinical Studies with Grading of Recommendations, Assessment, Development, and Evaluation Tool

We evaluated the quality of evidence from phase III/IV clinical trials of drugs against obesity using the principles of Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Our systematic review evaluates the quality of clinical evidence from existing clinical trials and not the pharmacological efficacy of anti-obesity therapies. A literature search using select keywords in separate was performed in PubMed and ClinicalTrials.gov databases for phase III/IV clinical trials during the last ten years. Our findings indicate that the quality of existing clinical evidence from anti-obesity trials generally ranges from low to moderate. Most trials suffered from publication bias. Less frequently, trials suffered from the risk of bias mainly due to lack of blindness in the treatment. Our work indicates that additional higher-quality clinical trials are needed to gain more confidence in the estimate of the effect of currently used anti-obesity medicines, to allow more informed clinical decisions, thus reducing the risk of implementing potentially ineffective or even harmful therapeutic strategies.

PSUN113 Evaluating The Efficacy Of Anti-Obesity Medications In a Multidisciplinary Weight Management Clinic At a VA Medical Center

Abstract Objective Anti-obesity medications have been shown to be effective in multiple randomized clinical trials, but there is limited data on the efficacy of these medications in the veteran population. This study was aimed to evaluate the effectiveness of anti-obesity medications in a multidisciplinary weight management clinic at our VA medical center. Methods This was a retrospective, descriptive study of 98 patients seen in a multidisciplinary weight management clinic at our VA medical center between January 1, 2019 and October 31, 2021. General requirements to be seen in the clinic were a BMI &amp;gt;30 or BMI &amp;gt;27 with comorbid conditions. Patients seen at least twice in the clinic were included in the study. Patients who received anti-obesity medications (phentermine-topiramate, naltrexone-bupropion, or GLP-1 receptor agonist (liraglutide or semaglutide)) had weights recorded at medication start date and at 2-4 months, 4-8 months, 8-10 months, and 10-14 months intervals. Baseline BMI, HbA1c, LDL-C and triglycerides were recorded at the medication start and followed up at similar intervals. Results There were 98 participants (56% males) within this study, with mean age of 54.9 years, mean baseline weight of 127.3 kg, and BMI of 43.5. Of all 98 patients seen in the clinic (regardless of being on anti-obesity medicine), 85 experienced some weight loss with 39 losing at least 5% of their body weight. The average weight loss from first to last visit was 4.1%. There were 72 patients who received anti-obesity medications for at least 3 consecutive months, including 12 patients who were subsequently trialed on a second class of anti-obesity medication. There were 35 trials of Qsymia, 43 trials of GLP-1 receptor agonists, and 6 trials of naltrexone-bupropion. For those patients receiving medications, average weight loss at 2-4 months was 3.7% (N=73), 4-8 months was 4.9% (N=58), 8-10 months was 6.0% (N=32), and 10-14 months was 5.5% (N=29). The percentage of patients able to lose at least 5.0% of their weight was 30.1% at 2-4 months, 43.1% at 4-8 months, 68.8% at 8-10 months, and 51.7% at 10-14 months. There was a decrease noted in HbA1c and LDL-C at all time periods, while there was no change in triglycerides. Conclusion Our data shows the effectiveness of anti-obesity medications in a veteran population seen in a multidisciplinary weight management clinic, though to a lesser extent as compared to clinical trials. Given the higher prevalence of multiple chronic conditions seen in veterans when compared to the general population, these patients have additional challenges when trying to achieve their weight loss goals. Further study must be performed to determine the long-term effectiveness and tolerability of these medications in this population. The differential effects among the anti-obesity medications should also be investigated further. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Chloroquine modulates the sulforaphane anti-obesity mechanisms in a high-fat diet model: Role of JAK-2/ STAT-3/ SOCS-3 pathway

The phytochemical sulforaphane (SFN) has been studied for its potential anti-obesity effect, but neither its molecular targets nor its interaction with the antimalarial drug chloroquine (CQ) has been fully delineated. Therefore, high-fat diet (HFD) obese rats were randomly allocated into one of five groups and were left untreated or gavaged orally with SFN (0.5 or 1 mg/kg), CQ (5 mg/kg), or their combination (0.5/5 mg/kg) for six successive weeks to assess their potential interaction and the enrolled mechanisms. SFN effectively reduced the HFD-induced weight gain, blood glucose, and serum leptin levels, and improved lipid profile. On the molecular level, SFN inhibited the lipogenesis-related enzymes, namely sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in both liver and visceral white adipose tissue (vWAT) of HFD obese rats. SFN also turned off the inflammatory pathway conserved Janus kinase/signaling transducers and activators of transcription/suppressor of cytokine signaling (JAK-2/STAT-3/SOCS-3) in these tissues, as well as the inflammatory markers nuclear factor-kappa (NF-κ) B and interleukin (IL)-22 in serum. In contrast, SFN downregulated the gene expression of microRNA (miR-200a), while significantly increasing the autophagic parameters; viz., beclin-1, autophagy-related protein (ATG)-7, and microtubule-associated protein 2 light chain 3 (LC3-II) in both liver and vWAT. On most of the parameters mentioned above, treatment with CQ solely produced a satisfactory effect and intensified the low dose of SFN in the combination regimen. These findings demonstrated the beneficial effects of using CQ as an add-on anti-obesity medicine to SFN.

Effects of the Antiobesity Drugs Aplex and Venera on Certain Biochemical and Physiological Indices in Obese Adult Male Albino Rats.

Background Because of the growing incidence of obesity, the use of synthetic antiobesity medicines as weight-loss agents has grown in popularity, although their usefulness has yet to be established. Two of such medicines are Aplex and Venera. This study is designed to determine the potential dangers of Aplex and Venera on certain biochemical and physiological indicators in obese adult male rats. Methods Twenty-one obese male albino rats (9 weeks old and having a body mass of 220 ± 20 g) were divided into three equal groups: the control group (vehicle treatment), the Aplex group (0.1 mg/kg/day) for 30 days, and the Venera group (0.1 mg/kg/day) for 30 days. Results The values of serum glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total protein, total cholesterol (TC), high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), TC/HDL ratio, testosterone, thyroxine (T4), and leptin did not differ significantly between the treated and control groups. In contrast, the treated groups had substantial changes in bodyweight, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), albumin, globulin, albumin/globulin ratio (A/G ratio), triglycerides (TG), low-density lipoproteins (LDL), LDL/HDL ratio, urea, creatinine, and triiodothyronine (T3) levels. Conclusion The findings indicate that Aplex and Venera have negative impacts on crucial biochemical and physiological indicators, particularly liver and kidney functioning.

RNA-seq profiling of white and brown adipocyte differentiation treated with epigallocatechin gallate

Due to serious adverse effects, many of the approved anti-obesity medicines have been withdrawn, and the selection of safer natural ingredients is of great interest. Epigallocatechin gallate (EGCG) is one of the major green tea catechins, and has been demonstrated to possess an anti-obesity function by regulating both white and brown adipose tissue activity. However, there are currently no publicly available studies describing the effects of EGCG on the two distinct adipose tissue transcriptomes. The stromal vascular fraction (SVF) cell derived from adipose tissue is a classic cell model for studying adipogenesis and fat accumulation. In the current study, primary WAT and BAT SVF cells were isolated and induced to adipogenic differentiation in the presence or absence of EGCG. RNA-seq was used to determine genes regulated by EGCG and identify the key differences between the two functionally distinct adipose tissues. Taken together, we provide detailed stage- and tissue-specific gene expression profiles affected by EGCG. These data will be valuable for obesity-related clinical/basic research.

Hexane extract of Curcuma longa L. inhibits the activities of key enzymes and pro- inflammatory adipokines linked to obesity

IntroductionObesity is associated with chronic activation of low-grade inflammation produced mainly from adipose tissue, which is implicated in the pathogenesis of several diseases. Consequently, there is a need to screen for new anti-obesity medicines. Clinical evidence regarding the anti-obesity properties of Curcuma longa L. (C. longa) is inconclusive. Therefore, we aimed to investigate for the first time the influence of curcuminoids and hexane extract derived from C. longa 1) On the release of pro-inflammatory adipokines from human abdominal subcutaneous adipose tissue (ASAT) and induced-mononuclear cells (iMC) and 2) On the activities of α-amylase, α-glucosidase, and lipase enzymes. MethodsASAT explants and lipopolysaccharide-iMC were treated with either curcuminoids or hexane extract of C. longa. Protein concentration, anti-lipase, anti-amylase and anti-glucosidase activities were evaluated employing colorimetric methods. ResultsTreatment of ASAT with curcuminoids or hexane extract inhibited the secretion of leptin, CCL5 and Il-1β. Treatment of iMC cells with curcuminoids or hexane extract inhibited the secretion of TNF-α, CCL5 and Il-1β and leptin was not detected. Curcuminoids possessed a significant inhibitory activity against lipase, α-amylase and α-glucosidase in a dose-dependent manner. ConclusionWe demonstrate for the first time that curcuminoids and C. longa exert anti-inflammatory properties on human ASAT and iMC and inhibit the activities of lipase, α-amylase and α-glucosidase enzymes. This suggests that C. longa and curcuminoids not only may ameliorate obesity-associated comorbidities such as metabolic syndrome but may be used as a preventive approach against obesity. However, this requires in vivo validation.

Current Options and Future Directions for NAFLD and NASH Treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved treatment. NAFLD accounts as a major causing factor for the development of hepatocellular carcinoma (HCC), and its incidence rises accompanying the prevalence of obesity and diabetes. Reprogramming of antidiabetic and anti-obesity medicine is a major treatment option for NAFLD and NASH. Liver inflammation and cellular death, with or without fibrosis account for the progression of NAFLD to NASH. Therefore, molecules and signaling pathways involved in hepatic inflammation, fibrosis, and cell death are critically important targets for the therapy of NAFLD and NASH. In addition, the avoidance of aberrant infiltration of inflammatory cytokines by treating with CCR antagonists also provides a therapeutic option. Currently, there is an increasing number of pre-clinical and clinical trials undergoing to evaluate the effects of antidiabetic and anti-obesity drugs, antibiotics, pan-caspase inhibitors, CCR2/5 antagonists, and others on NAFLD, NASH, and liver fibrosis. Non-invasive serum diagnostic markers are developed for fulfilling the need of diagnostic testing in a large amount of NAFLD cases. Overall, a better understanding of the underlying mechanism of the pathogenesis of NAFLD is helpful to choose an optimized treatment.

Anti-Obesity Medications in Cancer Therapy: A Comprehensive Insight.

The interplay between cancer and obesity is multifactorial and complex with the increased risk of cancer development in obese individuals posing a significant threat. Obesity leads to the upregulation or hyperactivation of several oncogenic pathways in cancer cells, which drives them towards a deleterious phenotype. The cross-talk between cancer and obesity is considered a large contributing factor in the development of chemotherapeutic drug resistance and the resistance to radiotherapy. The link between obesity and the development of cancer is so strong that a medication that demonstrates effectiveness against both conditions would serve as an essential step. In this context, anti-obesity medications provide a worthy list of candidates based on their chemo-preventive potential and chemotherapeutic properties. The current study focuses on exploring the potential of anti-obesity medicines as dual anticancer drugs. These medications target several key signaling pathways (e.g., AMPK, PI3K/Akt/mTOR, MAPK, NF-κB, JNK/ERK), which prove to be crucial for both cancer growth and metastases. Some of these drugs also play an important role in attenuating the signaling and cellular events which incite cancer-obesity cross-talk and demonstrate efficient counteraction of neoplastic transformation. Thus, this review highlights a comprehensive view of the potential use of anti-obesity medicines to treat both cancer and obesity for patients exhibiting both comorbities.

Anti-Obesity Medication Prescriptions by Race/Ethnicity and Use of an Interpreter in a Pediatric Weight Management Clinic

Background: Healthcare disparities associated with race/ethnicity and low English proficiency are well established in the US. We sought to determine if there are race/ethnic differences in anti-obesity medication prescription rates among youth with severe obesity (body mass index (BMI) ≥1.2 times the 95th percentile and/or BMI ≥35 kg/m2) treated in a pediatric weight management clinic (PWMC). We secondarily sought to determine if, among youth from families in whom English was not the primary language, there are differences in prescription rates between those using an interpreter during visits and those not. Methods: We reviewed electronic health records of youth 2–18 years old with severe obesity seen at a PWMC from 2012–2020. Race/ethnicity was self-reported and categorized as Non-Hispanic White (NHW), Hispanic/Latino, Non-Hispanic Black (NHB), Asian, American Indian/Alaska Native and Mixed. Anti-obesity medicines included stimulants (i.e. phentermine, lisdexamfetamine), topiramate, naltrexone (± bupropion), and glucagon-like peptide-1 agonists. We used Poisson regression models with robust standard errors to compare incidence rates of medicine prescription (incidence rate ratio (IRR), accounting for visit frequency) within the first 1 and 3 years of being followed in a PWMC. We controlled for age, baseline degree of obesity (percent of the 95th BMI percentile (%BMIp95)), number of obesity-related comorbidities (i.e. insulin resistance, hypertension, fatty liver), area-level socioeconomic status (median household income based on ZIP code), and interpreter use. We repeated similar analyses among families in whom English was not the primary language, comparing those using an interpreter with those not. Results: From 2012–2020, 1258 youth (mean age 11.8 years; %BMIp95 143%) were seen in our PWMC (57% NHW, 19% Hispanic/Latino, 16% NHB) of which 26% were prescribed anti-obesity medication. 86% primarily spoke English and 5.2% used an interpreter. There were no statistically significant differences in the IRR of prescriptions by race/ethnicity at 1 and 3 years; however, although not statistically significant point estimates suggest Hispanic/Latino youth being prescribed medication less often at 1 (IRR 0.71; p=0.08) and 3 (IRR 0.75; p=0.13) years compared to NHW. Among non-primary English speakers, rates of prescriptions were higher at 1 (IRR 5.7; p<0.01) and 3 (IRR 3.5; p<0.01) years in those using an interpreter versus those not. Conclusions: We found no significant race/ethnic differences in anti-obesity medication prescriptions; however, Hispanic/Latino youth received fewer prescriptions, albeit not statistically significant. Among non-primary English speakers, use of an interpreter was associated with increased prescriptions. Our results suggest that addressing healthcare disparities and language barriers may improve care delivery for youth with obesity.

Cardiovascular effects of antiobesity drugs: are the new medicines all the same?

Waiting for a definite answer from well-designed randomized prospective clinical trials, the impact of the new antiobesity drugs -liraglutide, bupropion/naltrexone, phentermine/topiramate and lorcaserin- on cardiovascular outcomes remains uncertain. What has been learned from previous experience with older medicines is that antiobesity drugs may influence cardiovascular health not only causing weight reduction but also through direct actions on the cardiovascular system. Therefore, in the present review, we examine what is known, mainly from preclinical investigations, about the cardiovascular pharmacology of the new antiobesity medicines with the aim of highlighting potential mechanistic differences. We will show that the two active substances of the bupropion/naltrexone combination both exert beneficial and unwanted cardiovascular effects. Indeed, bupropion exerts anti-inflammatory effects but at the same time it does increase heart rate and blood pressure by potentiating catecholaminergic neurotransmission, whereas naltrexone reduces TLR4-dependent inflammation and has potential protective effects in stroke but also impairs cardiac adaption to ischemia and the beneficial opioid protective effects mediated in the endothelium. On the contrary, with the only exception of a small increase in heat rate, liraglutide only exerts favorable cardiovascular effects by protecting myocardium and brain from ischemic damage, improving heart contractility, lowering blood pressure and reducing atherogenesis. As far as the phentermine/topiramate combination is concerned, no direct cardiovascular beneficial effect is expected for phentermine (as this drug is an amphetamine derivative), whereas topiramate may exert cardioprotective and neuroprotective effects in ischemia and anti-inflammatory and antiatherogenic actions. Finally, lorcaserin, a selective 5HT2C receptor agonist, does not seem to exert significant direct effects on the cardiovascular system though at very high concentrations this drug may also interact with other serotonin receptor subtypes and exert unwanted cardiovascular effects. In conclusion, the final effect of the new antiobesity drugs on cardiovascular outcomes will be a balance between possible (but still unproved) beneficial effects of weight loss and "mixed" weight-independent drug-specific effects. Therefore comparative studies will be required to establish which one of the new medicines is more appropriate in patients with specific cardiovascular diseases.