Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis evaluates their comparative efficacy and safety. Methods: A literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Included clinical trials addressed MASLD or MASH with Resmetirom, FGF21 analogs, or GLP-1 agonists. Statistical analyses used a random-effects model, calculating mean differences (MD) and relative risks (RR), with heterogeneity assessed using τ², I², and Q statistics. Results: MASH resolution was significantly higher for FGF21 (RR 4.84, 95% CI: 2.59 to 9.03), Resmetirom showed the most significant reduction in MRI-PDFF (MD −18.41, 95% CI: −23.60 to −13.22) and >30% fat reduction (RR 3.56, 95% CI: 2.41 to 5.26). Resmetirom significantly reduced ALT (MD −15.71, 95% CI: −23.30 to −8.13), AST (MD −12.28, 95% CI: −21.07 to −3.49), and GGT (MD −19.56, 95% CI: −34.68 to −4.44). FGF21 and GLP-1 also reduced these markers. Adverse events were significantly higher with Resmetirom (RR 1.47, 95% CI: 1.24 to 1.74), while GLP-1 and FGF21 showed non-significant trends towards increased risk. Conclusions: Resmetirom and FGF21 show promise in treating MASLD and MASH, with Resmetirom particularly effective in reducing liver fat and improving liver enzymes. GLP-1 agonists also show benefits but to a lesser extent. Further long-term studies are needed to validate these findings and assess cost-effectiveness.

Clopidogrel is an antiplatelet drug used to prevent recurrent ischemic events after acute coronary syndrome and/or coronary stent implantation. Single nucleotide polymorphisms (SNPs) such as CYP2C19*2 and ABCB1 C3435T have been found to play a role in different individual responses to clopidogrel. Since the prevalence of these SNPs is generally known to differ from one population to another, the aim of this study was to examine their prevalence in both a Palestinian and Turkish population. One hundred unrelated Palestinian subjects and 100 unrelated Turkish subjects were analyzed for CYP2C19*2 and ABCB1 C3435T polymorphisms by the amplification refractory mutation system (ARMS). Results showed an ABCB1 3435 T allele frequency of 0.46 (95% CI 0.391 to 0.529) in the Palestinian sample and 0.535 (95% CI 0.4664 to 0.6036) in the Turkish sample. CYP2C19*2 allele frequency was 0.095 (95% CI 0.0558 to 0.134) in the Palestinian sample and 0.135 (95% CI 0.088 to 0.182) in the Turkish sample. Our results provide information about the prevalence of the polymorphisms related to clopidogrel response in both the Palestinian and Turkish populations, in order to improve the safety and efficacy of clopidogrel through use of genetically guided, individualized treatment. The prevalence of these clinically significant alleles shed light on the importance of testing them before prescribing clopidogrel.

Aim: To compare the efficacy and safety profiles of recent innovations in type 2 diabetes mellitus (T2DM), which include once‐weekly formulations such as tirzepatide, a dual glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide receptor agonist, and once‐weekly insulin options such as icodec and basal insulin Fc. Methods: A systematic search of the PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The network meta‐analysis protocol was registered at OSF registries ( https://osf.io/gd67x ). The primary outcome of interest was change in glycated haemoglobin (HbA1c), with change in fasting plasma glucose (FPG), body weight, incidence of hypoglycaemia, and treatment discontinuation as secondary outcomes. Results: Tirzepatide exhibited superior efficacy in reducing HbA1c levels compared with insulin therapies, with the 15‐mg dose showing the most significant reduction (mean difference [MD] −1.27, 95% confidence interval [CI] −1.49; −1.0). In terms of FPG reduction, tirzepatide 15 mg ranked highest (MD −0.70, 95% CI −1.05; −0.34), followed by tirzepatide 10 mg and 5 mg. Additionally, tirzepatide led to substantial weight loss, with the 15‐mg dose exhibiting the most pronounced effect (MD −12.13, 95% CI −13.98; −10.27). However, a higher incidence of adverse events (AEs) and treatment discontinuation were associated with tirzepatide, particularly at higher doses. Conclusion: Tirzepatide, particularly at higher doses, demonstrates superior efficacy in lowering HbA1c and reducing hypoglycaemia risk compared with weekly insulin. However, its use is also associated with a higher incidence of AEs and treatment discontinuation.

Background: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. Objectives: This study compares the efficacy and tolerability of once-weekly insulin analogs (icodec and BIF) with once-weekly GLP-1/GIP agonists (semaglutide, exenatide, tirzepatide, dulaglutide) in managing type 2 diabetes mellitus (T2DM). Methods: We conducted a network meta-analysis (NMA) using data from randomized controlled trials (RCTs) that compared these treatments with a baseline of daily basal insulin. Primary outcomes included changes in HbA1c, body weight, and tolerability. Results: The analysis integrated data from 25 RCTs, involving 18,257 patients. Tirzepatide significantly outperformed other treatments in reducing HbA1c and promoting weight loss. Weekly insulins, compared to GLP-1/GIP agonists, showed a more tolerable profile and were beneficial for certain patient demographics emphasizing weight stability. Conclusion: Our findings suggest that while once-weekly GLP-1/GIP agonists provide superior glycemic control and weight management, weekly insulins offer viable options for patients prioritizing fewer side effects and weight stability. This comprehensive comparison aids in refining personalized treatment strategies for T2DM management.

Visual impairment due to inherited ophthalmic disorders is amongst the most common disabilities observed in populations practicing consanguineous marriages. Here we investigated the molecular genetic basis of an unselected broad range of ophthalmic disorders in 20 consanguineous families from Arab villages of Israel and the Palestinian Authority. Most patients had little or very poor prior clinical workup and were recruited in a field study. Homozygosity mapping followed by candidate gene sequencing applying conventional Sanger sequencing or targeted next generation sequencing was performed in six families. In the remaining 14 families, one affected subject per family was chosen for whole exome sequencing. We discovered likely disease-causing variants, all homozygous, in 19 of 20 independent families (95%) including a previously reported novel disease gene for congenital nystagmus associated with foveal hypoplasia. Moreover, we found a family in which disease-causing variants for two collagenopathies — Stickler and Knobloch syndrome — segregate within a large sibship. Nine of the 19 distinct variants observed in this study were novel. Our study demonstrated a very high molecular diagnostic yield for a highly diverse spectrum of rare ophthalmic disorders in Arab patients from Israel and the Palestinian Authority, even with very limited prior clinical investigation. We conclude that ‘genetic testing first' may be an economic way to direct clinical care and to support proper genetic counseling and risk assessment in these families.