Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors

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Abstract
Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non‐obese, non‐diabetic, non‐smoking, middle‐aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within‐patient comparison. Metformin decreased total and LDL‐cholesterol (P< 0.01), triglyceride (P< 0.01), fasting plasma insulin (P< 0.01) and C‐peptide levels (P< 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P< 0.001). Tissue plasminogen activator (t‐PA) activity increased (P< 0.02), and t‐PA antigen decreased (P< 0.01), whereas plasminogen activator inhibitor (PAI‐1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.