ABSTRACT
INTRODUCTION: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is estimated to affect upto 70-80% of people with type 2 diabetes mellitus (T2DM). Although several anti-hyperglycemic drugs have been shown to be effective in such patients, there remains an unmet need for newer drugs. The objective of this meta-analysis was to analyze the effect of ipragliflozin on aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) levels in patients with T2DM. METHODS: A literature search on electronic databases was conducted to identify potential randomized clinical trials (RCT) as per predetermined study selection criteria. Mean difference (MD) was calculated using Cochrane review manager. RESULTS: Twelve studies were included in the meta-analysis, including 1349 subjects. Compared to the control group, ipragliflozin as a monotherapy showed a significant reduction in levels of ALT at week 12 (p = 0.02) and at week 24 (p = 0.007), GGT at week 12 (p < 0.00001). Ipragliflozin as an add-on therapy showed significant reduction in levels of AST at week 24 (p < 0.00001), ALT at week 12 (p = 0.002), ALT at week 24 (p < 0.00001), and GGT at week 24 (p < 0.00001). CONCLUSION: Findings suggest the beneficial effects of ipragliflozin on liver enzymes. Further large-scale RCTs are required to confirm ipragliflozin's role for liver-related conditions in T2DM.
Subject(s)
Alanine Transaminase , Aspartate Aminotransferases , Diabetes Mellitus, Type 2 , Glucosides , Hypoglycemic Agents , Thiophenes , gamma-Glutamyltransferase , Humans , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/metabolism , Diabetes Mellitus, Type 2/drug therapy , Drug Therapy, Combination , Fatty Liver/drug therapy , gamma-Glutamyltransferase/blood , Glucosides/therapeutic use , Glucosides/administration & dosage , Hypoglycemic Agents/therapeutic use , Liver/enzymology , Liver/drug effects , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Thiophenes/therapeutic useABSTRACT
INTRODUCTION: Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy. METHODS: A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone. RESULTS: The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), p = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), p = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), p = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), p = 0.99] compared to placebo. CONCLUSION: Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile. PROSPERO REGISTRATION NUMBER: CRD42023434883.
