Efficacy and safety of the combined metabolic medication, containing inosine, nicotinamide, riboflavin and succinic acid, for the treatment of diabetic neuropathy: a multicenter randomized, double-blind, placebo-controlled parallel group clinical trial (CYLINDER)

• Published in: BMJ open diabetes research & care Vol. 10; no. 3; p. e002785
• Main Authors: Kharitonova, Tatiana, Shvarts, Yury G, Verbovoy, Andrey F, Orlova, Natalia S, Puzyreva, Valentina P, Strokov, Igor A
• Format: Journal Article
• Language: English
• Published: England American Diabetes Association 01-06-2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Acids; Antidepressants; Antioxidants; Antioxidants - therapeutic use; Clinical trials; Diabetes; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetic Neuropathies; Diabetic Neuropathies - drug therapy; Diabetic neuropathy; Double-blind studies; Drugs; Emerging Technologies, Pharmacology and Therapeutics; Female; Foot diseases; Humans; Hypoglycemia; Inosine - therapeutic use; Insulin; Male; Metabolism; Nervous system; Niacinamide - adverse effects; Quality of life; Riboflavin - adverse effects; Succinic Acid - therapeutic use; Vitamin B; Russia; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diabetes Complications
• DOI: 10.1136/bmjdrc-2022-002785
• EISSN: 2052-4897

IntroductionAntioxidants 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 methodsIn 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) ˃5, 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.ResultsIn 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.ConclusionsThe combination of SINR effectively alleviates DPN symptoms in patients with type 2 diabetes.Trial registration numberClinicalTrials.gov Registry (NCT04649203; Unique Protocol ID: CTF-III-DM-2019).