Metformin NIDDM

Marfella, R., Acampora, R., Verrazzo, G., Ziccardi, P., De Rosa, N., Giunta, R., and Giugliano, D. (1996). Metformin improves hemodynamic and rheological responses to L-arginine in NIDDM patients. Diabetes Care 19, 934—939. 

Metformin improves glucose tolerance in NIDDM subjects by lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization). 

Indication Monotherapy and in combination with a sulfonylurea, metformin, or insulin when diet and exercise plus the single agent does not result in adequate glycemic control in patients with type 2 diabetes (non-insulin-dependent diabetes millitus, NIDDM). 

Johansen K. Efficacy of metformin in the treatment of NIDDM. Meta-analysis. Diabetes Care 1999 22(l) 33-7. 

Sulkin TV, Bosnian D, Krentz AJ. Contraindications to metformin therapy in patients with NIDDM. Diabetes Care 1997 20(6) 925-8. 

Phenformin is a hypoglycaemic (better to say antihyperglycaemic) agent that was formerly used in the treatment of NIDDM. It is associated with an unacceptably high incidence of lactacidosis that has often proved fatal. Metformin is still on the market in Canada and Europe, but the sul-phonylureas comprise the only class of oral agents that are commercially available for the treatment of Type-II diabetes in the United States. 

Insulin-stimulated glucose uptake measured during hyperinsulinaemic clamp studies was similar before and after metformin treatment. Thus, the ability of metformin to lower plasma glucose concentration in NIDDM does not appear to be secondary to an improvement in insulin action (Wu et al., 1990). 

Metformin treatment of patients with NIDDM led to an improvement in both glycaemic control and lipoprotein metabolism (Wu etal., 1990). Triglycerides are reduced by 40% in patients with hyperlipoproteinaemia. Metformin helps combat hypertriglyceridaemia (Bailey, 1992) and has been ascribed some vasoprotective properties (Bailey, 1992). Metformin prevents experimental atherosclerosis and induces structural changes in lipoproteins in experimental animals. The reduction in total and LDL cholesterol levels was shown for diabetic patients with hypercholesterolaemia (Rains et al., 1989 Pentikainen... 

There are three conditions for the clinical use of metformin as a glucose-lowering agent in patients with NIDDM (1) as a primary drug, (2) in combination with other oral hypoglycaemic agents such as sulphonylureas and acarbose, and (3) together with insulin after secondary sulphonylurea failure. 

Fig. 25. Mean plasma glucose and plasma insulin responses to oral glucose before ( ) and after (O) 1 week of metformin treatment in NIDDM patients. Plasma glucose concentrations decreased significantly. (Source Fantus and Brosseau, 1986.)...

In conclusion, it can be stated, that biguanides, preferably metformin, have been shown in innumerable clinical trials to be highly effective as antihyper-glycaemic drugs. Together with acarbose, they may be the first-choice drug for the treatment of obese hyperinsulinaemic, insulin resistant Type-II diabetics with dietary failure. They help to correct most of the unwanted aspects of the metabolic syndrome, which is felt to contribute most to the high mortality rate of NIDDM patients with heart disease. 

The therapeutic effects of acarbose and biguanides have been compared in Type-II diabetics (Pagano and Cavallo-Perin, 1990) and found to be nearly equally effective. The same was true in studies (by Schwedes et al. (1982), who compared acarbose and metformin in poorly controlled NIDDM, while Schoffling et al. (1982) reported that acarbose was even more effective than metformin. Drost et al. (1982) concluded from their studies, however, that there was no basic difference between the hypoglycaemic effects of acarbose and metformin. Petersen (1982) tested the efficacy of acarbose versus buformin in NIDDM. Acarbose was found to reduce postprandial but not fasting blood glucose levels and to be slightly less effective than buformin. 

Wu M-S, Johnston P, Sheu W H-H, et al. Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients. Diabetes Care 1990 13 1-8. 

Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. Diabetes Care 1993 16 621-629. 

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