Efficacy and Tolerability of Insulin Degludec Versus Other Long-acting Basal Insulin Analogues in the Treatment of Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

PURPOSE: The goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D). METHODS: Those randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A1c and fasting plasma glucose (FPG). The tolerability end point was the prevalence of hypoglycemia confirmed throughout the treatment period. FINDINGS: Data from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (-0.370 mmol/L; 95% CI, -0.473 to -0.267 mmol/L; P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D; the differences in the risks for severe hypoglycemia were not significant. IMPLICATIONS: Compared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

MicroRNA-494 inhibition alleviates acute lung injury through Nrf2 signaling pathway via NQO1 in sepsis-associated acute respiratory distress syndrome.

AIMS: Although therapeutic strategies for acute respiratory distress syndrome (ARDS) have achieved improvements, its mortality remains high. It has been reported that microRNAs (miRs) serve as therapeutic strategies for ARDS, while specific mechanisms of miR-494 remain poorly understood. Thus, the present study aimed to assess the effects of miR-494 on acute lung injury (ALI) in rat models of sepsis-associated ARDS and its regulatory mechanism. METHODS: Following establishment of sepsis-associated ARDS rat models, the ratio of wet to dry weight (W/D) in right lung tissues was detected. Moreover, the expression patterns of miR-494, NQO1 and Nrf2 were evaluated in left lung tissues of rats. The miR-494 was exogenously overexpressed in rats so as to analyze the effects of miR-494 on ALI, inflammatory response and oxidative stress. Meanwhile, the Nrf2 signaling pathway was activated in rats in order to show the regulatory mechanism of miR-494 in ALI. And the target gene of miR-494 was identified by dual-luciferase reporter assay. KEY FINDINGS: The findings firstly revealed upregulated miR-494, and enhanced inflammatory response, oxidative stress and ALI in rat models of sepsis-associated ARDS. Additionally, MiR-494 negatively regulated NQO1 and blocked the Nrf2 signaling pathway. Moreover, ectopic expression of miR-494 promoted inflammatory response, oxidative stress and ALI. However, the activation of Nrf2 signaling pathway reversed these effects of miR-494. SIGNIFICANCE: Our key findings highlight the value of miR-494 inhibition as a therapeutic target for sepsis-associated ARDS, as a result of miR-494 accelerated ALI in rats with sepsis-associated ARDS through NQO1-mediated inactivation of Nrf2 signaling pathway.