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)

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.Rese...

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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
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Summary:	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).
ISSN:	2052-4897 2052-4897
DOI:	10.1136/bmjdrc-2022-002785