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.

Critical Appraisal of Drug Promotional Literature in Accordance With WHO Guidelines.

Background Drug promotional literature (DPL) is used as a marketing tactic to publicize the introduction of new medications. As drug companies are promoting the literature for their brand products, bias is possible. Various studies have demonstrated that printed DPLs disseminated by pharmaceutical companies are typically skewed. Material and method A prospective, observational study was carried out in the outpatient departments of a tertiary care hospital to analyze the DPL of different pharmaceutical companies using WHO criteria for "Ethical criteria for medicinal drug promotion, 1988". Results Out of 192 DPLs analyzed, information regarding the generic name, brand name, amount of active ingredient, and manufacturer name was found in all the DPLs (100%). Though therapeutic uses were mentioned in 91% of DPLs, dosage schedule (regimen) was mentioned only in 60%. Drug safety information such as the side effects and significant adverse drug reactions, precautions and warnings, contraindications, and major drug interactions were present in 24%, 36%, and 20%, respectively. Address of the manufacturer and reference to scientific literature were present only in 63% and 53% of DPLs, respectively. References mainly were from journals, present in 71% of DPLs. Most of the claims made in DPLs were regarding efficacy (73%), followed by safety (34%).  Conclusion In our study, not a single DPL fulfilled all the nine WHO criteria. A doctor should rigorously evaluate study findings before prescribing because misleading and incorrect information is now frequently found in this literature.

Evaluation of the Antinociceptive Action of Simvastatin in Mice.

INTRODUCTION: Statins are well-established agents for dyslipidemia and have successfully been used for the prevention of coronary artery diseases for a long time; this is attributed not only to their lipid-lowering action but also to their pleiotropic actions. Recently many pleiotropic actions of statins have been explored, but very few studies were done to explore statins' antinociceptive action; therefore, the current study was planned to evaluate the antinociceptive activity of Simvastatin in different pain models in mice. MATERIALS AND METHODS: Antinociceptive activity of Simvastatin was evaluated by using Eddy's hot plate method (central analgesic model), acetic acid-induced writhing method (peripheral analgesic model), and biphasic formalin-induced paw licking method. Twenty-four mice were divided into four groups (n = 6 in each): Vehicle control group, simvastatin 5mg/kg, simvastatin 20mg/kg, and positive control group. RESULTS: In the hot plate method, as compared to the vehicle control group, Simvastatin 20mg/kg group showed a significant rise in the reaction time to the corresponding time interval (p<0.001). While the simvastatin 5mg/kg group did not show any significant analgesic activity in the hot plate test. In the acetic acid writhing method, both test groups show a significant delay in the onset of writhing and a decrease in the number of writhes as compared to the vehicle control group (P<0.001). While in the formalin test, both groups show dose-dependent analgesic activity in both the early and late phases. CONCLUSION: Simvastatin exhibits analgesic activity in both central as well as peripheral models of analgesia, but central analgesia shows only at higher concentrations. Similarly, it inhibits inflammatory pain more predominantly than neurogenic, and hence simvastatin can be used in inflammatory conditions like rheumatoid arthritis and osteoarthritis particularly when there is coexisting dyslipidemia.

Effect on Reaction Time in Primary Hypothyroid Patients Before and After Thyroxin Treatment.

Introduction Thyroid hormones play a crucial role in the proper functioning of the nervous system. Both T3 and T4 hormones have many significant actions on the neuromuscular system and brain. In hypothyroid patients, various neurological signs and symptoms such as weakness, fatigue, paresthesias, arthralgias, etc. may be seen. Reaction time is a good indicator of the processing of the central nervous system. So, our study aims to observe the change in reaction time in hypothyroid patients as compared to the control group. And to understand, if some difference is observed, how does it change after treatment with thyroxin in a hypothyroid group. Materials and methods This study was conducted at the tertiary care teaching hospital in the Vidarbha region. In this study, 40 newly diagnosed primary hypothyroid patients (including males and females), in the age group of 20 to 45 years, and whose thyroid-stimulating hormone (TSH) levels were between 10 and 50 mIU/L and free T4 levels below the normal level were included. A suitable comparable control group of the same demographic parameter was selected. Reaction time was taken before the start of thyroxin treatment in both groups, and results were analyzed by using an unpaired t-test. The reaction time of the hypothyroid group was again measured after eight weeks of the start of thyroxin treatment, it was compared with the initial reaction time, and data were compared by using the paired t-test. Result In the hypothyroid group as compared to the control group both auditory and visual reaction times were significantly on the higher side (p<0.05). Also, there was a significant improvement in reaction time after the start of thyroxin treatment (p<0.05), which suggests improvement in CNS activity in hypothyroid patients after initiation of therapy. Conclusion Thyroid hormones play a crucial role in the proper functioning and processing of the central nervous system. Due to this reason, reaction time in hypothyroid patients was on the longer side, showing a slowing of the nervous system when reacting to a specific stimulus. After thyroxin treatment for a sufficient period, reaction times were of shorter duration as compared to before the start of thyroxin, which shows well-recovered nervous activity. Therefore, reaction time is not only used as a handy tool to identify early central nervous system manifestations of hypothyroidism but also used to monitor response to treatment.

KIT (CD117) Positive Huge Primary Malignant Extra Gastrointestinal Stromal Tumors (EGISTs) Arising From Jejunal Mesentery: A Rare Case Report.

Tumors arising outside gastrointestinal systems are known as extra gastrointestinal stromal tumors (EGISTs). Outside gastrointestinal sites include the mesentery, omentum, peritoneum, pancreas, and liver. Our case highlights a rare occurrence of an EGIST in jejunal mesentery in a 45-year-old male with an asymptomatic large abdominal growth and weight loss. A contrast-enhanced multi-dimensional computed tomography scan showed a large heterogeneous mass in the left hypochondrium. lumbar, and paraumbilical regions. Later, the patient underwent surgical resection of the tumor along with the involved jejunal segment and small tumor masses in the mesentery. Histopathological examination reported a malignant EGIST of mesentery and invasion into the jejunum, further confirmed by immunohistochemistry (IHC) markers like CD117 and smooth muscle actin with a high proliferative index (Ki67). One should be aware that these are different from other malignancies arising from the mesentery. Their cell of origin is different and needs a specific type of treatment. The clinical history, radiological findings, histopathology, and IHC help in diagnosing especially when they are arising from unusual areas like jejunal mesentery. Surgical intervention and chemotherapy are mainstay treatments.