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

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 less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 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.

The effect of metformin on blood pressure and metabolism in nondiabetic hypertensive patients

“…Thus, we were neither able to support nor rule out the previously suggested beneficial effect of metformin on BP in insulin-resistant hypertensives [6] or obese female subjects [7].…”

“…Studies of the effect of metformin on blood pressure in NIDDM patients are not conclusive [5]. In most studies of the effect in nondiabetic subjects [6][7][8][9], both plasma insulin and blood pressure (BP) are reduced. Especially in the pilot study of Landin et al [6], a large reduction of BP was observed during metformin treatment.…”

Plasma insulin, plasminogen activator inhibitor, and ankle-brachial systolic blood pressure ratio in overweight hypertensive subjects

“…[44][45][46][47] Treating insulin resistance with metformin reduces together the glucose disposal in response to insulin and the altered fibrinolytic activity. 48,49 In the present study, although insulin and PAI antigen were significantly correlated, it seems likely that both insulin and PAI antigen influenced the ABI ratio, but only insulin played a significant role in treated subjects. Since the population was treated by various antihypertensive agents, further studies are needed to clarify the druginduced links between the ABI and PAI antigen.…”

The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension.

“…Landin et al 54 reported that 6 weeks of oral administration of metformin, a biguanide, to insulin-resistant, hypertensive men increased insulin sensitivity and significantly decreased arterial pressure (e.g., diastolic pressure fell by -24±5 mm Hg). The authors emphasized that this was a pilot, uncontrolled study.…”