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Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T0), 1 month (T1) and 2 months (T2) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p<0.001) during monotherapy with metformin vs. placebo and T0 group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p<0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T2 group in comparison with T0 group (p<0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11601679&dopt=Abstract
Diabetes Care. 1983 Sep-Oct;6(5):472-4.
Diarrhea and metformin in a diabetic clinic.
Dandona P, Fonseca V, Mier A, Beckett AG.
Department of Chemical Pathology, Royal Free Hospital, London, England.
In a questionnaire-based survey of 285 randomly selected diabetic patients, diarrhea was found to occur in 8%; this was found to be similar to that in 150 nondiabetic control patients attending other medical clinics (8%). When the diabetic patients were divided into separate therapeutic groups, metformin-treated (with or without sulfonylureas) patients had a markedly greater prevalence of diarrhea (20%) than those not on this drug (6%). A majority of patients with metformin-associated diarrhea had soiling of clothes as a problem, while at least two complained of frank loss of control over their anal sphincter. These patients did not have autonomic neuropathy, and in all who stopped this drug, diarrhea settled within 2-5 days. Only 6% of insulin-dependent diabetic individuals (IDD) had diarrhea, one of whom had explosive nocturnal stools with incontinence and features diagnostic of autonomic neuropathy. Metformin is by far the commonest cause of diarrhea and incontinence in our diabetic clinic, where it is used routinely. In contrast, diarrhea due to autonomic neuropathy is rare.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6336343&dopt=Abstract
Int J Clin Pharmacol Ther. 1996 Jan;34(1):43-6.
Utilization of antidiabetic drugs in Hong Kong: relation to the common occurrence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions and the relative prevalence of NIDDM.
Chan TY, Lee KK, Chan AW, Critchley JA.
Department of Clinical Pharmacology, Chinese University of Hong Kong, Shatin.
Antidiabetic drug-induced hypoglycemia as a cause of acute medical admissions is more common in Hong Kong (1.7%) than in other countries (0.1-0.5%). To determine if this higher incidence may be related to the frequent use of some sulphonylureas, we have studied the overall prescribing patterns in the public sector in 1994 by reviewing the utilization of antidiabetic drugs in the general out-patient/general practice clinics (GOPD) and Hospital Authority public hospitals and affiliated specialist clinics (HA). The vast majority of patients (90.5%) receiving antidiabetic treatment were taking sulphonylureas and/or metformin, confirming that diabetes mellitus in Hong Kong is predominantly of the noninsulin-dependent type. The GOPD and the HA each accounted for approximately half of the sulphonylureas (55% vs 45%) and metformin (43% vs 57%) prescribed. Glibenclamide (84.9% vs 79.1%, 83.7% overall) and gliclazide (12.8% vs 16.6%, 14.5% overall) were the 2 most frequently used sulphonylureas. Only 9.5% of patients on antidiabetic drugs were receiving insulin and 92% of this was prescribed by the HA. For comparison, Singapore has a similar prevalence of diabetes mellitus but a much lower incidence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions (0.5%). Tolbutamide was the most frequently used there sulphonylurea (66.6-72.2%) with glibenclamide only contributing 20.8-28.6%. Thus, the predominant use of glibenclamide in Hong Kong may contribute to the high incidence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8688996&dopt=Abstract
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