Unlocking the therapeutic potential and personalized therapy of testosterone: a comprehensive review.

INTRODUCTION: Testosterone, the primary male sex hormone, orchestrates various physiological processes including sex differentiation, development of male characteristics, sperm production, and fertility. Its synthesis primarily occurs in Leydig cells within the testes, with smaller contributions from the ovaries and adrenal glands, all derived from cholesterol. Current therapeutic use of testosterone is mainly confined to treating hypergonadotropic hypogonadism, with limited off-label usage for augmenting muscle growth. CONTENT: This review delves into numerous studies investigating testosterone's therapeutic potential across various medical conditions as depicted in the figure given below. SUMMARY: Of all the studies in this review, which show a positive therapeutic result by using testosterone, the most promising areas of potential usage of testosterone are anxiety and diabetes mellitus, followed by obesity and depression. OUTLOOK: By the medium if this study, we want to not only enlist the various potential therapeutic uses of testosterone, but also promote a optimal hormonal balance, which can lead to prevention and/or better treatment outcomes for the mentioned diseases.

Effects of probiotics on selected anthropometrics and biochemical measures in overweight or obese Saudi subjects: a double-blind, placebo-controlled, randomised clinical trial.

OBJECTIVE: This study aimed to assess the effects of multi-strain probiotics on anthropometric and biochemical measures in Saudi adults with overweight or obesity. DESIGN: Single-centre, double-blind, placebo-controlled, randomised clinical trial. SETTING: Occupational Health Clinics at King Saud University Medical City, Riyadh, Saudi Arabia. PARTICIPANTS: Ninety-three Saudi participants with overweight or obesity were randomly assigned to receive twice-daily doses of either placebo (n 49) or 30 × 109 CFU/g of HEXBIO® containing three Lactobacillus and three Bifidobacterium species (n 44) in a double-blind manner over a 12-week period, respectively. Both groups adhered to a hypoenergetic diet. Anthropometric measurements, glycaemic indices and lipid profiles were evaluated at baseline and post-intervention. RESULTS: Following the 12-week intervention, no statistically significant differences were found in all between the probiotic group and placebo group comparisons, except for fat intake, where the group*time interaction showed a significant decrease in favour of the probiotic group (P = 0·02). However, significant within-group reductions were observed in the probiotic group: body weight (-0·9 kg, P = 0·02), HC (-1·5 cm, P = 0·002), energy intake (-387·3 kcal/d, P = 0·002), fasting glucose (-0·7, P = 0·002) and LDL-cholesterol (-0·7, P = 0·02). CONCLUSION: Consumption of multi-strain probiotic supplementation over 12 weeks significantly decreased fat intake in Saudi adults with overweight or obesity, with the probiotic group highlighting improved anthropometric and biochemical parameters. Further research is needed to evaluate the long-term clinical significance of this dietary practice and whether it has a meaningful impact on overall health beyond the placebo effect.

Challenges in the care and treatment of patients with extreme obesity.

Obesity is a prevalent chronic disease. The management of extreme obesity - i.e., body mass index (BMI) ≥ 50 kg/m2 or obesity class IV and V - is still far from ideal. Individuals with extreme obesity have a high risk of surgical complications, mortality, comorbidities, and reduced weight loss following bariatric surgery. Although lifestyle changes and anti-obesity medications are recommended for all patients with extreme obesity as adjuvants to weight loss, these measures are less effective than bariatric surgery. As a first step, sleeve gastrectomy or an inpatient very-low-calorie diet should be incentivized to enhance weight loss before definitive surgery. Although malabsorptive procedures lead to greater weight loss, they are associated with an increased risk of early complications and malnutrition. Nonstandard techniques employed in clinical trial protocols, such as transit bipartition, may be performed as they maintain a weight loss potency comparable to that of the classic duodenal switch but with fewer nutritional problems. Anatomical causes should be investigated in patients with postoperative suboptimal clinical response or recurrent weight gain. In these cases, the initiation of anti-obesity drugs, endoscopic therapies, or a conversion procedure might be recommended. More studies are needed to address the specific population of patients with extreme obesity, as their outcomes are expected to be distinct from those of patients with lower BMI.

The risks and benefits of managing obesity in older adults.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: This review discusses weight loss considerations in overweight and obese older adults. SUMMARY: Current US guidelines do not address weight loss in older adults. Waist circumference rather than body mass index (BMI) may be a more accurate assessment tool for obesity in older adults. Weight loss interventions are not recommended in overweight older adults due to the decreased mortality in this population (known as the "obesity paradox"). While weight loss in obese older adults may be beneficial, it is not without risks. The greatest risks include loss of muscle mass, decline in bone mineral density, and development of sarcopenic obesity. Weight loss interventions may be considered in older adults with a BMI of greater than 30 kg/m2 who have metabolic derangements, cardiovascular disease, and/or functional impairments after carefully weighing the risks against the benefits of weight loss and the impact of interventions on the patient's quality of life. Medicare provides limited benefits for weight loss interventions. In older adults, there is no consensus on which lifestyle interventions are best for weight loss and there is a paucity of data on the use of weight loss medications. Careful consideration should be given before utilizing medications for weight loss in older adults given the enhanced adverse effect profiles, interactions, contraindications, and costs. CONCLUSION: Weight loss in older adults should be approached differently from that in the general adult population. More data are needed on the efficacy and safety of weight loss medications in older adults.

A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low-dose liraglutide in otherwise healthy men with overweight or obesity.

AIMS: Pharmacotherapeutic options for obesity treatment include glucagon-like peptide-1 receptor (GLP-1R) agonists, for example, liraglutide. However, an unmet need remains, particularly in patients with a high body mass index (BMI), as GLP-1R agonists are associated with gastrointestinal adverse events (AEs) and some patients do not respond to treatment. Neuropeptide Y (NPY) and peptide YY bind G-protein-coupled Y receptors and represent attractive targets for modulating bodyweight. MATERIALS AND METHODS: This first-in-human, three-part, partially blinded phase I study (NCT04903509) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of the peptidic NPY2R agonist BI 1820237, with/without low-dose liraglutide: part 1 (participants randomized to receive BI 1820237: 0.075-2.4 mg or placebo), part 2 (BI 1820237: 1.2 mg or placebo) and part 3 (BI 1820237: 0.025-1.2 mg + liraglutide 0.6 mg or placebo + liraglutide 0.6 mg). Primary endpoint is the proportion of participants with drug-related AEs. Secondary endpoints are tolerability, PK and PD. RESULTS: In total, 95 otherwise healthy men with increased BMI (25.0-34.9 kg/m2) were randomized. Drug-related AEs, mainly gastrointestinal events, were reported by 39.0% of participants (n = 23) in parts 1 + 2 and 30.6% of participants (n = 11) in part 3; one drug-related AE (11.1%, part 3) was reported in a participant receiving placebo with liraglutide. Post-dose paracetamol PK suggested that BI 1820237 and low-dose liraglutide exhibited additive effects on gastric emptying. CONCLUSIONS: BI 1820237 treatment was associated with transient nausea and vomiting at higher doses. No differences in tolerability were observed when combined with liraglutide; effects on gastric emptying appeared additive.

In vitro Evaluation of Anti-obesity Potential of Phyllanthus Fraternus Leaves.

Obesity has been an important health concern for over a decade, causing serious health issues worldwide. Treatments available for obesity include FDA-approved drugs such as Lorcaserin, Orlistat, Bupropion, combinations of Phentermine and Topiramate, and Sibutramine; however, these have adverse effects on health. To address the said issue, the current study was conducted to evaluate the anti-obesity potential of Phyllanthus fraternus leaves. These leaves are a rich source of different phytochemicals (e.g., alkaloids, saponins, terpenoids, tannins), and the plant has been shown to exhibit medicinal properties; therefore, it can be used for treating obesity disorders. The crude extract of plants was prepared in three different solvents (e.g., methanol, hydro alcohol, and isopropyl alcohol). Lipid inhibition was determined using lipase inhibition assay, and amylase assay was carried out to determine if the plant extract had anti-diabetic properties. An oil red staining was carried out to determine lipid accumulation in which the cells were incubated with plant extract for 48 h. To determine if the plant extract was toxic to 3T3 cells, an MTT assay was carried out to assess cell viability. Through lipase inhibition assay, we depicted potent anti-obesity properties, isopropyl alcohol extract exhibited 67.45% inhibition at the concentration of 500µg/ml. Methanol extract showed the highest percent of α amylase inhibition i.e., 90.03% at a concentration of 1,000 µg/ml. The MTT assay concluded that the plant extracts were not cytotoxic to the cells at a concentration range between 20µg/ml to 100µg/ml, and the percentage of viable cells was 98-63%. The results obtained from the current study revealed that the plant exhibits potent anti-obesity properties. Thus, this plant extract is a potential source as an alternative treatment to treat 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.

Changes in Food Waste among a Sample of U.S. Consumers after Beginning Anti-Obesity Medication.

BACKGROUND/OBJECTIVES: Glucagon-like peptide-1 agonists (GLP1As) are increasingly prescribed to treat obesity. While studies document how these medications impact dietary habits, their relationship to consumer food waste is unexplored. Approximately one-third of all food is wasted, which creates substantial economic and environmental damage. The purpose of this study is to assess how consumers alter food waste after beginning GLP1As and to identify factors associated with this relationship. METHODS: Retrospectively reported changes in the amount of food wasted since beginning a GLP1A are gathered from a sample of 505 U.S. consumers via a self-administered online survey. Regression analysis yields associations between changes in post-GLP1A-uptake food waste and the length and type of medication use, medication side effects, post-uptake changes in dietary habits, and respondent characteristics. RESULTS: A total of 25% of respondents agree they waste more food since beginning the medication, while 61% disagree. Respondents are significantly less likely to agree with this statement if they have been on the medication a longer time and are significantly more likely to agree if they reported experiencing nausea since beginning the medication. Dietary changes consistent with more vegetable intake are also significantly associated with less waste. CONCLUSIONS: Uptake of a novel class of anti-obesity medications may significantly affect food waste patterns. With the potential for widespread adoption of such medications, and given the societal import of reducing food waste, understanding the interaction of these two consumer trends is critical for projecting their joint impact on the food system and for equipping new GLP1A users to limit food waste.

Studies on the Probiotic, Adhesion, and Induction Properties of Artisanal Lactic Acid Bacteria: to Customize a Gastrointestinal Niche to Trigger Anti-obesity Functions.

The primary goals of this work are to explore the potential of probiotic lactic acid bacteria's (LAB) mucin/mucus layer thickening properties and to identify anti-obesity candidate strains that improve appropriate habitat for use with the Akkermansia group population in the future. The HT-29 cell binding, antimicrobial properties, adhesion to the mucin/mucus layer, growth in the presence of mucin, stability during in vitro gastrointestinal (GI) conditions, biofilm formation, and mucin/mucus thickness increment abilities were all assessed for artisanal LAB strains. Sixteen LAB strains out of 40 were chosen for further analysis based on their ability to withstand GI conditions. Thirteen strains remained viable in simulated intestinal fluid, while most showed high viability in gastric juice simulation. Furthermore, 35.9-65.4% of those 16 bacteria adhered to the mucin layer. Besides, different lactate levels were produced, and Streptococcus thermophilus UIN9 exhibited the highest biofilm development. In the HT-29 cell culture, the highest mucin levels were 333.87 µg/mL with O. AK8 at 50 mM lactate, 313.38 µg/mL with Lactobacillus acidophilus NRRL-B 1910 with initial mucin, and 311.41 µg/mL with Lacticaseibacillus casei NRRL-B 441 with initial mucin and 50 mM lactate. Nine LAB strains have been proposed as anti-obesity candidates, with olive isolates of Lactiplantibacillus plantarum being particularly important due to their ability to avoid mucin sugar consumption. Probiotic LAB's attachment to the colonic mucosa and its ability to stimulate HT-29 cells to secrete mucus are critical mechanisms that may support the development of Akkermansia.

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

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

Preliminary exploration of the C-3 galloyl group and the B-5' hydroxyl group enhance the biological activity of catechins in alleviating obesity induced by high-fat diet in mice.

Catechins, among the most active components in tea, effectively alleviate obesity. Catechins are primarily classified into four types based on the presence or absence of the C-3 galloyl group and the B-5' hydroxyl group. However, the impact of conformation on the anti-obesity properties of catechins remains unclear. Findings indicate that the C-3 galloyl group and the B-5' hydroxyl group significantly enhance the biological activity of catechins, aiding in obesity alleviation, regulating glycolipid metabolism, reducing hepatic steatosis, lowering serum lipopolysaccharide (LPS) levels, and promoting the proliferation of Akkermansia muciniphila. Further investigation revealed that Akkermansia muciniphila may modulate LPS/insulin resistance to protect glycolipid metabolic homeostasis, attenuate liver tissue damage, and promote catechin metabolism to generate new bioactive components. Overall, the C-3 galloyl group and the B-5' hydroxyl group may modulate the gut-liver axis through the bidirectional interplay between catechins and Akkermansia muciniphila, thereby enhancing the anti-obesity activity of catechins.

Updates in pharmacotherapy of obesity.

Obesity is now recognized as a chronic, progressive condition requiring early intervention and long-term management to achieve health benefits and improve metabolic risk factors. The main objective of obesity pharmacotherapy is weight loss and weight loss maintenance. There is increasing acceptance of anti-obesity medications as an adjunct to lifestyle modifications and/or surgery. In recent years there has been an evolution in management approach and pharmacologic options for treatment. As a result, there is increased focus on the efficacy and safety of these agents. We provide a historical perspective, review of recent studies on anti-obesity medication outcomes showing efficacy, potential side effects and promising therapies in development.

A review on drug repurposing applicable to obesity.

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

Targeted Nano-Based Systems for the Anti-Obesity Agent's Delivery.

Obesity is a global health concern and a chronic disease that is accompanied by excessive fat storage in adipose and nonadipose tissues. An increase in the body-mass index (BMI) is directly proportional to the 2- to 3.9-fold increase in all-cause mortality in obesity. If left untreated for a longer period, obesity-related metabolic, cardiovascular, inflammatory, and malignant diseases reduce life expectancy. Currently, most of the anti-obesity drugs have failed and fallen into disrepute, either due to their ineffectiveness or adverse effects. In this review, depending on their enhanced pharmacokinetic and biodistribution profiles, whether nanocarriers alter the basic properties and bioactivity of anti-obesity drugs used in clinical practice are debated. First, nanocarriers can improve the safety of still-used anti-obesity drugs by lowering their systemic toxicity through increasing targeting efficacy and preventing drug carrier toxicity. Second, when the micro-ribonucleic acids (miRNAs), which are aberrantly expressed in obesity and obesity-related diseases, are encapsulated into nanoparticles, they are effective in multiple obesity-related metabolic pathways and gene networks. Finally, a synergistic anti-obesity effect with low dose and low toxicity can be obtained with the combinatory therapy applied by encapsulating the anti-obesity drug and gene in the same nanocarrier delivery vehicle.

Anti-obesity and immunomodulatory effects of Allium hookeri leaves cultivated with artificial light of different intensities on immune-depressed obese mice.

This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 µmol/m2/s; M: medium, 150 µmol/m2/s; H: high, 200 µmol/m2/s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, ß-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity.

Complete genome sequence and anti-obesity potential of Lactiplantibacillus plantarum HOM2217 in 3T3-L1 cells and high-fat diet-fed rats.

The global prevalence of obesity is rising year by year, which has become a public health problem worldwide. Many animal and clinical studies have shown that Lactiplantibacillus plantarum is considered an ideal probiotic and potential supplement for the treatment of obesity. In this study, we aimed to complete the genome sequence of L. plantarum HOM2217, which was isolated from human milk, and study its physiological characteristics and anti-obesity effects in 3T3-L1 cells and rats fed a high-fat diet (HFD) to determine its potential as a starter for functional food products. Whole-genome analysis demonstrated that HOM2217 contained a single circular chromosome of 3,267,529 bp with a GC content of 44.5% and one plasmid (62,350 bp) with a GC content of 38.5%. Compared to the reference strains, HOM2217 demonstrated superior tolerance to gastrointestinal conditions, higher adhesion to intestinal epithelial cell lines, potent antimicrobial activity against Enterobacter cloacae ATCC 13047, and effective cholesterol removal ability in vitro. Treatment with heat-killed HOM2217 significantly reduced lipid accumulation and intracellular triglyceride production in 3T3-L1 adipocytes. Daily treatment of HFD-fed rats with HOM2217 for 7 weeks decreased body weight, body weight gain, and body fat without changes in food intake. HOM2217 also significantly increased the serum high-density lipoprotein cholesterol (HDL-C) level, decreased the serum tumor necrosis factor (TNF-α) and increased short-chain fatty acid (SCFA) (formic acid, acetic acid, and butyric acid) levels in the cecum. Thus, HOM2217 could potentially prevent obesity in rats by inhibiting inflammatory responses and regulating lipid metabolism and SCFAs expression. Therefore, HOM2217 has potential as an alternative treatment for obesity.

Anti-Obesity Medication in the Management of Children and Adolescents With Obesity: Recent Developments and Research Gaps.

BACKGROUND: Paediatric obesity is a global public health concern. While in most countries the incidence keeps rising, the need for effective and long-term management for children and adolescents living with this chronic, relapsing disease is pressing. Health behaviour and lifestyle treatment (HBLT) is recommended as first-line treatment. METHODS: Narrative review. RESULTS: A new generation of recently approved anti-obesity medications (AOM) now has the potential to fill the gap between limited effects on body mass index (BMI) by HBLT alone and large effects by metabolic and bariatric surgery in adolescents with obesity aged 12 years and older. While, for semaglutide and phentermine/topiramate, effectiveness is substantial with relevant, but mostly mild to moderate adverse events, there is a gap in evidence regarding long-term effects and safety, effects on outcomes beyond BMI reduction and data for certain groups of patients, such as children < 12 years and minority groups. When integrating AOM treatment into national healthcare systems it should be offered as part of a comprehensive patient-centred approach. CONCLUSION: This article summarizes recent AOM developments, integration into paediatric obesity management, and identifies research gaps.

The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Adolescents Without Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have become the leading anti-obesity drugs for adults, and a similar trend may follow in adolescents with its recent approval for this age group. However, there is a lack of comparative analysis on the weight loss effects and safety of GLP-1 RAs in obese or overweight pediatric and adolescent populations, especially those who are non-diabetic. This systematic review and meta-analysis aim to provide current evidence on the efficacy and safety of GLP-1 RAs as an anti-obesity treatment in obese or overweight non-diabetic pediatric and adolescent populations. METHOD:  We searched electronic databases from inception until January 2024 for randomized controlled trials (RCTs) that analyzed the weight loss effect of GLP-1 receptor agonists in adolescents with obesity or overweight without diabetes mellitus. Search results were screened, and eligible studies were included to perform a systematic review and meta-analysis using the Review Manager (RevMan) computer program Version 5.4.1 (The Cochrane Collaboration, 2020) with a random-effects model. The primary efficacy outcomes were changes in body weight, BMI, and BMI Z-score, while the secondary outcomes were the incidence of gastrointestinal adverse events, treatment discontinuation rate due to adverse events, and incidence of serious adverse events. The mean difference, odds ratio, and 95% confidence interval (CI) were used to present the meta-analysis results. Publication bias was visualized using a funnel plot. The quality of the studies was analyzed using Cochrane's Risk of Bias tool (RoB2). RESULTS: A total of seven RCTs with 576 adolescent participants were included in the analysis. GLP-1 RAs significantly achieved greater weight loss than placebo, with a mean difference of -4.98 kg (-8.49, -1.46), I² = 99%, p = 0.006. Subgroup analysis showed that semaglutide had the most pronounced anti-obesity effect (mean difference of -17.70 kg (-18.89, -16.51), p < 0.00001), compared to liraglutide (mean difference of -2.26 kg (-5.17, 0.65), I² = 99%, p = 0.13) and exenatide (mean difference of -3.17 kg (-4.45, -1.90), I² = 0%, p < 0.0001). Similar results were obtained for other efficacy parameters such as BMI and BMI z-score. However, GLP-1 RA was associated with more gastrointestinal adverse events (such as nausea and vomiting) than placebo (3.06 (2.12, 4.42), I² = 0%, p < 0.00001), with incidence comparable among all GLP-1 RAs in the subgroup analysis. The overall risk of bias among included studies was either of 'some concern' or 'high risk.' CONCLUSIONS: Our meta-analysis demonstrated that GLP-1 RAs had a superior anti-obesity effect compared to placebo or lifestyle modification in obese or overweight non-diabetic adolescents, particularly semaglutide, which had a more pronounced anti-obesity effect than liraglutide and exenatide, with tolerable gastrointestinal adverse effects.

Pharmacological management of polycystic ovary syndrome.

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m2). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions.