RESUMEN
INTRODUCTION: Antioxidants may have positive impact on diabetic polyneuropathy (DPN), presumably due to alleviation of oxidative stress. We aimed to evaluate the efficacy and safety of combination of antioxidants: succinic acid, inosine, nicotinamide, and riboflavin (SINR) in the treatment of DPN. RESEARCH DESIGN AND METHODS: In a double-blind, placebo-controlled clinical trial, men and women aged 45-74 years with type 2 diabetes and symptomatic DPN, with initial Total Symptom Score (TSS) Ë5, were randomized into experimental (n=109) or placebo (n=107) group. Patients received study medication/placebo intravenously for 10 days, followed by oral administration for 75 days. Statistical significance was defined as a two-tailed p<0.05. RESULTS: In SINR group, mean TSS change after 12 weeks was -2.65 (±1.46) vs -1.73 (±1.51) in the placebo group (p<0.0001; t-test). Reduction of symptoms in the SINR group was achieved regardless of hemoglobin A1c levels, but better results were observed in patients with initial TSS <7.5. The analysis of TSS subscores revealed statistically significant between-group differences by dynamics of the intensity of paresthesia and of numbness starting from day 11 (p=0.035 and p=0.001, respectively; mixed model); by day 57, statistically significant between-group differences were detected also by dynamics of burning intensity (p=0.005; mixed model). Study limitations are small effect size, moderate proportion of patients with severe DPN symptoms, subjective assessment of outcomes, exclusion of participants who received injectable glucose-lowering medications other than insulins, and patients with uncontrolled and type 1 diabetes. CONCLUSIONS: The combination of SINR effectively alleviates DPN symptoms in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04649203; Unique Protocol ID: CTF-III-DM-2019).
Asunto(s)
Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Femenino , Humanos , Masculino , Antioxidantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Inosina/uso terapéutico , Niacinamida/efectos adversos , Riboflavina/efectos adversos , Ácido Succínico/uso terapéuticoRESUMEN
AIM: To assess the efficacy and safety of ipragliflozin as add-on therapy to metformin in Russian patients with type 2 diabetes mellitus. METHODS: In this double-blind study conducted in 14 centers in Russia, 165 patients were randomized 2:1 to ipragliflozin (50â¯mg/day) or placebo for 24â¯weeks while continuing metformin. Patients who had HbA1câ¯≥â¯7.0% (53â¯mmol/mol) at Week 12 received open-label ipragliflozin (50â¯mg/day) in addition to the blinded drug from Week 12-24. RESULTS: Significant reductions in HbA1c and body weight from baseline to Week 12 in favor of ipragliflozin were observed (adjusted mean difference to placebo: -0.3% (-3 mmol/mol), Pâ¯=â¯0.048 and -1.34â¯kg, Pâ¯<â¯0.001, respectively). The incidence of AEs was similar in both groups. Uptitration to 100â¯mg/day ipragliflozin led to a further reduction in body weight (mean change from Week 12: -0.65â¯kg, Pâ¯=â¯0.004) and an additional 13% (9/69) of patients achieving HbA1câ¯<â¯7.0% (53â¯mmol/mol) at Week 24. Incidence of AEs was similar among patients receiving ipragliflozin 50â¯mg/day (23.7%) and 100â¯mg/day (24.6%). CONCLUSION: Ipragliflozin 50â¯mg/day added to metformin significantly reduced HbA1c and body weight after 12â¯weeks and showed a safety profile comparable to placebo. Uptitration to 100â¯mg/day improved clinical outcomes with no additional safety concerns.