Combination Treatment with a Novel Polyherbal Formulation and Metformin: A Single Blind Placebo-Controlled Study in Patients with T2DM and Cognitive Impairments
DOI:
https://doi.org/10.17140/DROJ-1-116Keywords:
Neurodegeneration, Type 2 diabetes, Polyherbal formulation, Metformin Combination treatment.Abstract
Background: Older people suffering from Type 2 Diabetes Mellitus (T2DM) are at major risk for age related cognitive dysfunction and dementia, mainly due to vascular complications. Studies have shown that T2DM is also associated with Alzheimer’s Disease (AD) and is responsible for accelerating the pathology through insulin resistance. A polyherbal drug containing Bacopa Monnieri, Hippophae rhamnoides and Dioscorea bulbifera has shown a potent neuroprotective effect in management of cognitive deficits in elderly; and metformin a well-accepted antidiabetic agent responsible for lowering blood glucose in T2DM, can together provide an intriguing
potential combination therapy for prevention and amelioration of cognitive impairments in T2DM patients. Objective: The present study is aimed to evaluate the combined effect of a polyherbal drug and metformin on improving cognitive functions in patients suffering from T2DM. Method: Elderly patients with an age range of 60-75 years diagnosed for T2DM were enrolled in the study and randomized into two groups; Group I=T2DM patients given metformin and placebo, Group II=T2DM patients given metformin and polyherbal drug. The subjects received the combination therapy of metformin (500 mg) and placebo or metformin (500 mg) and polyherbal drug (500 mg) twice daily for a period of 24 weeks. Estimation of Mini Mental State Examination (MMSE) score, blood glucose, HbA1c, insulin, lipid profile (total cholesterol, LDL-c, HDL-c, triglycerides), homocysteine, Interleukin-6 (IL-6), TNF-α and C-reactive protein (CRP) were measured at baseline and were repeated at three months and six months. The primary end point was a change from baseline to week 24 in MMSE score. Key secondary end points included change from baseline to week 24 in Digital Symbol Substitution (DSS); subtest of the Wechsler Adult Intelligence Scale-Revised), word recall (digital memory apparatus – Medicaid systems, Chandigarh, India), attention span (Attention Span Apparatus – Medicaid systems, Chandigarh, India), Functional Activity Questionnaire (FAQ) and Hamilton Depression Scale (HDS) score. Further inflammatory markers and level of oxidative stress were analysed using standard biochemical tests. Result: The trial was performed in 120 elderly diabetic patients out of whom 112 patientscompleted the study for 24 weeks. Statistically significant differences were found between the two groups after intervention
on cognitive performance indicated by MMSE, DSS, word recall, attention span, FAQ, HDS, and memory span scores; inflammatory
markers such as C-reactive protein (CRP), interleukin- 6 (IL-6), Interferon-α (INF-α) and Tumor necrosis factor-α (TNF-α); oxidative stress markers like Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Glutathione (GSH) and Thiobarbituric acid reactive substances (TBARS); and neurodegeneration marker Homocysteine (Hcy). However, no significant variations were indicated between groups in serum insulin and HbA1c levels after intervention of 24 weeks. Conclusion: The results of this study demonstrate the therapeutic potential of the combination therapy of a polyherbal drug and metformin. These results also support longer trials of this combination therapy for patients with mild cognitive impairment and diabetes.
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