Efficacy and safety of orlistat in controlling the progression of prediabetes to diabetes: A meta-analysis and systematic review.

BACKGROUND: The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy and safety in preventing the progression to diabetes. METHODS: For achieving the appropriate randomized controlled trials, we enrolled the public datas from the following electronic databases: The Cochrane library, Embase, China National Knowledge Infrastructure, VIP, Wan-Fang, and China Biology Medicine disc. The article focused on the orlistat intervention of glucose tolerance and glycemic status in prediabetic patients. We restricted the publication time from the creation to May 2023. RESULTS: Six subjects were included in the study, with a total of 1076 participants (532 in the control group vs 544 in the experimental group). The results indicated that the orlistat can reduce the fasting blood glucose [relative risk (RR) = -2.18, 95% confidence intervals (CI) (-2.471, -1.886)], as well as the 2 hour postprandial blood glucose [RR = -1.497, 95% CI (-1.811, -1.183)]. Furthermore, it can prevent the impaired glucose tolerance patients to type 2 diabetes mellitus [RR = 0.605, 95% CI (0.462, 0.791)], and reversal the impaired glucose tolerance [RR = 2.092, 95% CI (1.249, 3.503)]. CONCLUSIONS: In prediabetic people, the orlistat can control weight, reduce the fasting blood glucose and the 2 hour postprandial blood glucose, and then delay the progression of diabetes. However, due to the quantitative restrictions, additional high-quality study needs to be conducted to improve the reliability of the results.

The corrective role of superparamagnetic iron oxide nanoparticles for the genes controlling hypothalamus-pituitary-testis-axis in male obesity-associated secondary hypogonadism.

Background: Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields. Aim: In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). Methods: 42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMC-SPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments. Results: The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitary-testicular-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25-50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. Conclusion: CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms.

[Current State of Pharmacotherapy in Obesity].

The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective treatment tools are required. Many advances in obesity treatment have been reported recently, including lifestyle modifications and pharmacological, endoscopic, and surgical treatments. Drugs with proven long-term efficacy and safety are preferred because management for obesity treatment is a long-term process. Currently, four medications are available for long-term use in Korea: Orlistat, Naltrexone/bupuropion NR, Phentermine/topiramate capsule, and Liraglutide. Recently, semaglutide and tirzepatide have been attracting attention because of their effectiveness and convenience, but they are not yet available in Korea. In addition, there are limitations such as the yo-yo effect when discontinuing the drug, long-term safety, and cost. Patients and medical staff must be aware of the advantages and side effects of each medication to ensure the successful treatment of obesity.

Comparison of the Efficacy of Anti-Obesity Medications in Real-World Practice.

Purpose: Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting. Patients and Methods: The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit. Results: A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area. Conclusion: All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.

Anti-obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta-analysis to inform the 2023 international evidence-based guideline.

This systematic review and meta-analysis evaluated the efficacy of anti-obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in polycystic ovary syndrome (PCOS) to inform the 2023 update of the International Evidence-based Guideline on PCOS. We searched Medline, EMBASE, PsycInfo, and CINAHL until July 2022 with a 10-year limit to focus on newer agents. Eleven trials (545 and 451 participants in intervention and control arms respectively, 12 comparisons) were included. On descriptive analyses, most agents improved anthropometric outcomes; liraglutide, semaglutide and orlistat appeared superior to placebo for anthropometric outcomes. Meta-analyses were possible for two comparisons (exenatide vs. metformin and orlistat + combined oral contraceptive pill [COCP] vs. COCP alone). On meta-analysis, no differences were identified between exenatide versus metformin for anthropometric, biochemical hyperandrogenism, and metabolic outcomes, other than lower fasting blood glucose more with metformin than exenatide (MD: 0.10 mmol/L, CI 0.02-0.17, I2 = 18%, 2 trials). Orlistat + COCP did not improve metabolic outcomes compared with COCP alone (fasting insulin MD: -8.65 pmol/L, -33.55 to 16.26, I2 = 67%, 2 trials). Published data examining the effects of anti-obesity agents in women with PCOS are very limited. The role of these agents in PCOS should be a high priority for future research.

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

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

Association of patient characteristics and insurance type with anti-obesity medications prescribing and fills.

AIM: To characterize factors associated with the receipt of anti-obesity medication (AOM) prescription and fill. MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2015 to 30 June 2023, in a large health system in Ohio and Florida. Adults with a body mass index ≥30 kg/m2 who attended ≥1 weight-management programme or had an initial AOM prescription between 1 July 2015 and 31 December 2022, were included. The main measures were a prescription for an AOM (naltrexone-bupropion, orlistat, phentermine-topiramate, liraglutide 3.0 mg and semaglutide 2.4 mg) and an AOM fill during the study follow-up. RESULTS: We identified 50 678 adults, with a mean body mass index of 38 ± 8 kg/m2 and follow-up of 4.7 ± 2.4 years. Only 8.0% of the cohort had AOM prescriptions and 4.4% had filled prescriptions. In the multivariable analyses, being a man, Black, Hispanic and other race/ethnicity (vs. White), Medicaid, traditional Medicare, Medicare Advantage, self-pay and other insurance types (vs. private insurance) and fourth quartile of the area deprivation index (vs. first quartile) were associated with lower odds of a new prescription. Hispanic ethnicity, being a man, Medicaid, traditional Medicare and Medicare Advantage insurance types, liraglutide and orlistat (vs. naltrexone-buproprion) were associated with lower odds of AOM fill, while phentermine-topiramate was associated with higher odds. Among privately insured individuals, the insurance carrier was associated with both the odds of AOM prescription and fill. CONCLUSIONS: Significant disparities exist in access to AOM both at the prescribing stage and getting the prescription filled based on patient characteristics and insurance type.

Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective.

OBJECTIVES: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC). METHODS: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m2, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime. RESULTS: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained. CONCLUSION: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.

The effect of orlistat in the treatment of non-alcoholic fatty liver in adolescents with overweight and obese.

Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P = < 0.001), steatosis score (P = 0.001), NAFLD activity score (P = < 0.001), weight (P = < 0.001), body mass index (BMI) (P = < 0.001), waist circumferences (WC) (P = < 0.001), BMI-Z score (P = < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P = < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders. CONCLUSION: The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. TRIAL REGISTRATION: (Clinical trial registry number: IRCT20220409054467N2, with a registration date of 2022-05-13). WHAT IS KNOWN: • Among the interventions of interest for the management of pediatric NAFLD, we can mention lifestyle and pharmaceutical measures. WHAT IS NEW: • This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. • The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks.

Potential anti-obesity effects of two-graded doses of Iraqi Hibiscus tiliaceus leaves extract, alone and in combination with orlistat, on high-fat diet-induced obesity in male rats.

Obesity is a world health concern and a serious risk factor for several chronic diseases. Hibiscus tiliaceus is a plant with reported anti-obesity properties. However, the preclinical anti-obesity effect of ethanolic extract of Iraqi Hibiscus tiliaceus has not been studied yet. This study aimed to evaluate the preclinical anti-obesity properties of Iraqi Hibiscus tiliaceus extract, alone or in combination with orlistat, on high-fat diet-induced obesity in male rats. Male rats were divided into five groups: control, induction, ethanolic extract of Iraqi Hibiscus tiliaceus (250 mg/kg and 500 mg/kg), orlistat (Xenical) alone (10 mg/kg), and a combination of the extract (250 mg/kg) with Xenical. The rats were fed a high-fat diet to induce obesity, and treatments were given orally for 8 weeks. Body weight, food intake, serum lipid profile, and liver enzymes were measured. Administration of ethanolic extract of Iraqi Hibiscus tiliaceus (250 mg/kg and 500 mg/kg), Xenical alone (10 mg/kg), and combination with the extract (250 mg/kg) for 8 weeks significantly reduced body weight, food intake, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and liver enzymes (aspartate transaminase and alanine transaminase) when compared to the induction group. The ethanolic extract of Iraqi Hibiscus tiliaceus showed anti-obesity effects and could be a potential therapeutic agent in managing obesity. However, further studies are needed to evaluate its clinical efficacy and safety.

Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma.

BACKGROUND: Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages. METHODS: In this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection. RESULTS: FABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1-/- mice consistently showed attenuation. The FABP1-/- group's relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo. CONCLUSIONS: ScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.

Pharmacoeconomic evaluation of anti-obesity drugs for chronic weight management: a systematic review of literature.

Introduction: Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and Drug Administration (FDA) for chronic weight management. The aim of this paper is to investigate the pharmacoeconomic evaluation of AODs through a systematic review with a special focus on methodological considerations. Methods: We searched the general and specific databases to identify the primary pharmacoeconomic evaluation of AODs. Results: A total of 18 full-text articles and three conference abstracts were included in this review. Most of the economic assessments were still about Orlistat. And the observations we could make were consistent with the previous systematic review. A few studies were on the combined therapies (i.e. PHEN/TPM ER and NB ER) compared to different comparators, which could hardly lead to a generalized summary of the cost-effectiveness. Most recently, pharmacoeconomic evidence on the newest GLP 1 RA approved for the indication of obesity or obesity with at least one comorbidity emerged gradually. Modelling-based cost-utility analysis is the major type of assessment method. In the modelling studies, a manageable number of the key health states and the state transitions were structured to capture the disease progression. In particular, the principal structure of the decision model adopted in the three studies on the newly approved drug was nearly the same, which enables more in-depth comparisons and generalizations of the findings. Conclusion: This study provided an up-to-date overview of the strengths and areas for improvement in the methodological design of the pharmacoeconomic evaluation of the licensed drugs for chronic weight management. Future modelling evaluations would benefit from a better understanding of the long-term weight loss effects of the current therapeutic options and the weight rebound process after the discontinuation of treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302648, identifier CRD42022302648.

Cost-Effectiveness of Antiobesity Drugs for Adolescents With Severe Obesity.

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Pharmacological effect and mechanism of orlistat in anti-tumor therapy: A review.

Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity. In addition to being regarded as a slimming drug, a growing number of studies in recent years have suggested that orlistat has anti-tumor activities, while the underlying mechanism is still not well elucidated. This paper reviewed recent pharmacological effects and mechanisms of orlistat against tumors and found that orlistat can target cancer cells through activation or suppression of multiple signaling pathways. It can induce tumor cells apoptosis or death, interfere with tumor cells' cycles controlling, suppress fatty acid synthase activity, increase ferroptosis, inhibit tumor angiogenesis, and improve tumor cells glycolytic. Thus, this review may shed new light on anti-tumor mechanism and drug repurposing of orlistat, and anti-tumor drug development.

Comparison of orlistat and orlistat plus metformin therapy between diabetic and nondiabetic groups.

OBJECTIVE: The objective of this study was to examine the effects of orlistat use on metabolic control and weight loss in diabetic and nondiabetic patients. METHODS: A total of 119 patients with body mass index≥40 kg/m2 and receiving orlistat therapy, who applied to the Endocrinology polyclinic between January 2016 and October 2019, were included. The patients' weight changes and biochemical values (i.e., fasting glucose, HbA1c, ALT, creatinine, and lipid parameters) were evaluated at the drug beginning and the last polyclinic control. The patients were divided into groups, whether they had diabetes or used metformin, and compared. RESULTS: The mean age of the 119 patients in the study was 45.3±11.5 years. A total of 94.1% of the patients were females and 5.9% were males. A total of 38.7% of the patients had diabetes and 29.4% had prediabetes. When the patients were compared to whether they had diabetes or used metformin, there was a statistically significant difference between the groups according to weight loss. The mean weight change of patients without diabetes and receiving metformin and orlistat was statistically significantly higher than that of patients with diabetes and receiving metformin and orlistat. DISCUSSION: It was determined that the weight loss effect of orlistat in obesity was seen in all groups, but this effect decreased in the diabetic group.

Successful Treatment of Cirrhotic Chylous Ascites using Orlistat and Dietary Modifications: A Case Study and Literature Review.

BACKGROUND Chylous ascites (chyloperitoneum), a condition arising from lymphatic leakage in the peritoneal cavity, is rare in liver cirrhosis patients, accounting for less than 1% of cases. Treatment typically involves therapeutic paracentesis, dietary modifications, a low-fat, high-protein diet, and medium-chain triglyceride (MCT) supplementation. Orlistat, a fat absorption inhibitor, has been reported to show potential efficacy in treating chylous ascites. CASE REPORT We detail the case of a 59-year-old male patient admitted for decompensated liver disease and worsening ascites. Diagnostic paracentesis identified chylous ascites, indicated by a 3.5 mmol/L triglyceride level. Despite administering therapeutic paracentesis, dietary modifications, MCT supplementation, Spironolactone, and Terlipressin for a presumed hepatorenal syndrome, the patient's ascites remained chylous for two weeks. On administering orlistat, a significant reduction in ascites volume and chylous content was observed, with triglyceride levels dropping to 0.7 mmol/L. CONCLUSIONS Our case illustrates the potential of orlistat in managing chylous ascites in liver cirrhosis patients, marking only the second such case reported in the existing literature. It encourages further exploration of orlistat's therapeutic potential in treating chylous ascites.

[Renal Damage and Obesity: a Silent Pairing].

Obesity is recognized as a true chronic disease and an independent risk factor for kidney disease. In particular, a correlation was observed between obesity and the development of focal segmental glomerulosclerosis. The clinical consequences of obesity on the kidney can include albuminuria, nephrotic syndrome, nephrolithiasis, and increased risk of development and progression of renal failure. Conventional therapy, which includes low-calorie diet, exercise, lifestyle changes, and drug therapy, including GLP1-RA, phentermine, phentermine/topiramate, bupropion/naltrexone, orlistat, is not always able to achieve the desired results and above all does not guarantee stabilization of body weight over time. On the other hand, bariatric surgery is giving excellent results in terms of efficacy and duration. Bariatric surgery techniques that are generally divided into restrictive, malabsorptive, and mixed are not free from possible metabolic complications such as anemia, vitamin deficiency, and stones. However, they are able to ensure a good maintenance of weight loss obtained with disappearance or reduction of the incidence and severity of comorbidities related to obesity.

Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet.

BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats.

Orlistat mouth rinse: Using the tongue to deliver antiobesity medication in a double-blind randomized crossover pilot trial.

AIM: To investigate the effects of an orlistat mouth rinse on the intake of a high-fat meal. METHODS: A double-blind, balanced order, crossover study was conducted in participants (n = 10, body mass index 25-30 kg/m2 ) assigned to receive placebo or orlistat (24 mg/mL) prior to a high-fat meal. Participants were divided into low- or high-fat consumers based on calories consumed from fat following placebo administration. RESULTS: The orlistat mouth rinse decreased total and fat calories consumed during the high-fat meal in high-fat consumers, and did not alter calories consumed in low-fat consumers (P < 0.05). CONCLUSIONS: Orlistat decreases long-chain fatty acid (LCFA) absorption by inhibiting lipases that breakdown triglycerides. Orlistat mouth rinse decreased fat intake in high-fat consumers, suggesting that orlistat inhibited the detection of LCFAs from the high-fat test meal. Lingual delivery of orlistat is predicted to eliminate the risk of oil incontinence and promote weight loss in individuals who prefer fat.

Artemisia annua L. (Sweet wormwood) leaf extract attenuates high-fat diet-induced testicular dysfunctions and improves spermatogenesis in obese rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L., known as "sweet wormwood," is widely used in Egyptian folk medicine. Egyptians implement the aerial parts in the treatment of respiratory, digestive and sexual dysfunctions. However, the mechanism by which Artemisia annua improves testicular function is still being discovered. AIM OF THE STUDY: This study aimed to evaluate the modulatory effects of the crude leaf extract of Artemisia annua (AAE) on a high-fat diet induced testicular dysfunction in rats and compare it with the antilipolytic drug Orlistat. MATERIAL AND METHODS: Forty adult rats were randomly classified and assigned to four groups. The first group typically consumed a balanced diet and served as a negative control (GP1). A high-fat diet-induced obesity was applied to the other three groups for 12 weeks. A positive control remained on HFD for another 8 weeks, which is GP2. Other groups were administered for 8 consecutive weeks either with Orlistat (50 mg/kg body weight) or AAE (100 mg/kg body weight), which have been defined as GP3 and GP4, respectively. Testosterone (TST), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the sera of all groups. In addition, the oxidant/antioxidant biomarkers such as protein carbonyl, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) activities, lactate dehydrogenase (LDH) and creatine kinase isoenzyme-B (CK-MB) were determined. An immunohistochemical stain with the apoptotic marker caspase-3 and the proliferating cell nuclear antigen (PCNA) were also investigated. RESULTS: In the testes of the obese group, the results showed hormonal imbalance, an increase in oxidative stress biomarkers and apoptosis. In the group treated with orlistat (GP3), noticeably more perturbations were noted. The obese rats that had been treated with AAE (GP4) showed a significantly reduced level of oxidative stress, hormonal balance restoration and reduced apoptosis. CONCLUSIONS: The crude leaf extract of A. annua is a potential herbal therapeutic for the treatment of obesity-related testicular dysfunction and the restoration of hormonal imbalance in obese rats.