Ipragliflozin L-Proline

Type 2 diabetes mellitus (T2DM) and obesity are growing global health concerns, particularly in older adults who are at higher risk of sarcopenia. While sodium‐glucose cotransporter 2 (SGLT2) inhibitors show promise for glycemic control and weight loss, their effects on muscle health remain unclear. We examined the effects of SGLT2 inhibitors on body weight, fat mass, and muscle mass in T2DM patients. We systematically searched the PubMed, Embase, Scopus, and Cochrane databases for relevant randomized controlled trials (RCTs). Three reviewers screened the studies, and two extracted data and assessed their quality. R software was used to evaluate heterogeneity via Cochran's Q and I2 statistics. Eight RCTs ( n  = 541) were included. SGLT2 inhibitors significantly reduced body weight (standardized mean difference (SMD) = −0.85, p  < 0.001; I2  = 0%) and fat mass (SMD = −0.53, p  < 0.001; I2  = 51.1%). A small reduction in muscle mass was observed (SMD = −0.35, p  < 0.001; I2  = 22.9%), though substantially smaller than fat loss. Subgroup analysis confirmed that fat mass was reduced with dapagliflozin/ipragliflozin (SMD = −0.67, p  < 0.001; I2  = 26.4%) and empagliflozin (SMD = −0.53, p  < 0.001; I2  = 66.4%). SGLT2 inhibitors effectively reduce body weight primarily through fat loss in older adults. Although muscle mass declined modestly, the predominance of fat loss suggests weight reduction occurs through favorable metabolic changes. Given the slight muscle mass changes and study heterogeneity, careful monitoring in older adults is warranted, and further studies in diverse populations are needed.

This study aimed to conduct the first network meta-analysis (NMA) comparing the effectiveness of sodium-glucose transporter 2 (SGLT-2) inhibitors-dapagliflozin, empagliflozin, and ipragliflozin-in improving liver-related and metabolic outcomes in patients with nonalcoholic fatty liver disease (NAFLD), utilizing a robust Bayesian NMA framework.

We conducted a systematic review and Bayesian NMA of randomized controlled trials (RCTs) up to December 31, 2024, following Preferred Reporting Items for Systematic Reviews and Network Meta-Analyses guidelines. Databases (PubMed, Cochrane Library, Scopus, Embase) were searched for RCTs involving NAFLD patients (with or without type 2 diabetes) treated with SGLT-2 inhibitors versus placebo/standard treatments. Outcomes included alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fibrosis-4 score, body weight, and fasting plasma glucose. A random-effects Bayesian NMA was performed using a Markov Chain Monte Carlo method, with treatments ranked via Surface Under the Cumulative Ranking Curve (SUCRA) scores.

Eleven RCTs (805 patients) were included. Dapagliflozin led in alanine aminotransferase (mean difference [MD]: -11.35 IU/L, 95% CrI: -18.39 to -4.19, SUCRA: 84.87%), aspartate aminotransferase (MD: -7.96 IU/L, 95% CrI: -15.69 to -0.18, SUCRA: 81.70%), and body weight reduction (MD: -3.60 kg, 95% CrI: -5.92 to -1.64, SUCRA: 88.88%). Ipragliflozin excelled in gamma-glutamyl transferase (MD: -15.19 IU/L, 95% CrI: -31.25 to -2.11, SUCRA: 81.35%) and fasting plasma glucose reduction (MD: -2.20 mmol/L, 95% CrI: -9.88 to 5.30, SUCRA: 59.79%). Empagliflozin topped fibrosis-4 score reduction (MD: -0.12, 95% CrI: -0.42 to 0.13, SUCRA: 73.27%).

SGLT-2 inhibitors significantly improve liver and metabolic outcomes in NAFLD, with dapagliflozin, ipragliflozin, and empagliflozin offering distinct benefits, supporting personalized treatment strategies.