Snorgaard O, Køber L, Carlsen J
Department of Cardiology and Endocrinology, Frederiksberg Hospital, Copenhagen, Denmark.
J Intern Med. 1997 Nov;242(5):407-12. doi: 10.1046/j.1365-2796.1997.00236.x.
To study the effect of metformin on blood pressure and metabolism in nondiabetic hypertensives.
A six-week single-blind placebo wash-out, followed by a double-blind placebo-controlled parallel group design with skew randomization (2:2:1) to metformin 850 mg b.i.d. (n = 10), metformin 500 mg b.i.d. (n = 10), or placebo b.i.d. (n = 5) for 12 weeks. Office blood pressure (oBP), ambulatory blood pressure (aBP), lipoproteins, and oral glucose tolerance (OGTT) were measured/performed before and during treatment.
Sixteen male and nine female nondiabetic (OGTT) patients (median age 57 (39-74) years) with verified hypertension (White-coat excluded) for 4 (0-20) years.
The possible effect of metformin treatment and dosage was tested with a two-factor analysis of variance. Treatment induced a significant decline in diastolic oBP, P < 0.05. This decline was, however, not significantly different comparing metformin and placebo. Systolic oBP, diastolic aBP, and systolic aBP showed no significant change by treatment. The decline in diastolic oBP was 5 mmHg in the pooled group of metformin-treated patients, P < 0.005. Different gender and the presence of obesity had no impact on the decline in diastolic oBP within this group. Changes in fasting C-peptide and fasting insulin during treatment were unrelated to blood pressure changes. High fasting insulin (> 60 pmol L[-1]) or high fasting C-peptide (> 1000 pmol L[-1]) at baseline did not favour an effect of metformin on diastolic oBP. Glucose metabolism and lipoproteins were unchanged in all groups.
Although metformin treatment induced a decline in diastolic office blood pressure in nondiabetic hypertensives, the decline was not different from that during placebo treatment. Metformin had no significant effect on ambulatory blood pressure. Thus, metformin has, if any, only a minor clinically insignificant effect on blood pressure in nondiabetic hypertensives. The study does not support the hypothesis that circulating insulin is a major regulator of blood pressure in hypertension.
研究二甲双胍对非糖尿病高血压患者血压及代谢的影响。
为期六周的单盲安慰剂洗脱期，随后采用双盲安慰剂对照平行组设计，并通过偏态随机化（2:2:1）将患者分为三组，分别给予二甲双胍850毫克每日两次（n = 10）、二甲双胍500毫克每日两次（n = 10）或安慰剂每日两次（n = 5），治疗12周。在治疗前及治疗期间测量/进行诊室血压（oBP）、动态血压（aBP）、脂蛋白及口服葡萄糖耐量试验（OGTT）。
16名男性和9名女性非糖尿病（OGTT）患者（年龄中位数57（39 - 74）岁），确诊高血压（排除白大衣高血压）4（0 - 20）年。
采用双因素方差分析检验二甲双胍治疗及剂量的可能效果。治疗导致舒张压oBP显著下降，P < 0.05。然而，二甲双胍组与安慰剂组相比，这种下降无显著差异。收缩压oBP、舒张压aBP及收缩压aBP在治疗后无显著变化。二甲双胍治疗组患者的舒张压oBP下降了5 mmHg，P < 0.005。该组内不同性别及肥胖情况对舒张压oBP的下降无影响。治疗期间空腹C肽和空腹胰岛素的变化与血压变化无关。基线时高空腹胰岛素（> 60 pmol L[-1]）或高空腹C肽（> 1000 pmol L[-1]）并不利于二甲双胍对舒张压oBP产生作用。所有组的糖代谢和脂蛋白均无变化。
尽管二甲双胍治疗可使非糖尿病高血压患者的诊室舒张压下降，但该下降与安慰剂治疗期间的下降无差异。二甲双胍对动态血压无显著影响。因此，二甲双胍对非糖尿病高血压患者的血压即便有影响，也仅具有轻微的临床无显著意义的作用。该研究不支持循环胰岛素是高血压中血压主要调节因子这一假说。
