Does metformin cause high blood pressure
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The Impact of Metformin on Blood Pressure: A Comprehensive Review
Introduction to Metformin and Blood Pressure
Metformin is a widely used medication for managing type 2 diabetes mellitus (T2DM). While its primary function is to control blood glucose levels, there has been considerable interest in understanding its effects on blood pressure (BP). This article synthesizes findings from various studies to determine whether metformin causes high blood pressure or has any significant impact on BP.
Metformin and Blood Pressure in Animal Models
Antihypertensive Effects in Fructose-Fed Rats
Research on fructose-fed hyperinsulinemic, hypertensive rats has shown that metformin can prevent increases in both plasma insulin levels and systolic blood pressure. In this study, metformin-treated rats on a fructose-enriched diet exhibited significantly lower systolic BP compared to untreated rats, suggesting that metformin has antihypertensive properties in this model.
Salt-Induced Hypertension in Spontaneously Hypertensive Rats
Another study demonstrated that metformin attenuates salt-induced hypertension in spontaneously hypertensive rats. The treatment blunted the rise in BP caused by a high-salt diet, indicating that metformin can mitigate hypertension exacerbated by high salt intake.
Clinical Trials and Human Studies
Randomized Clinical Trials in Hypertensive Patients
A randomized clinical trial involving hypertensive patients without diabetes found no significant difference in BP reduction between the metformin and placebo groups. This suggests that metformin may not have a direct BP-lowering effect in non-diabetic hypertensive patients.
Blood Pressure in Offspring of Women with Gestational Diabetes
A follow-up study from the MiG trial assessed BP in children born to women treated with metformin for gestational diabetes. The results showed no significant difference in BP between children whose mothers were treated with metformin versus insulin, indicating that maternal metformin use does not adversely affect BP in offspring.
Orthostatic Blood Pressure Recovery
A sub-study from the Copenhagen Insulin and Metformin Therapy (CIMT) trial indicated that metformin might adversely affect orthostatic blood pressure recovery in patients with T2DM. The study found an increased early drop in orthostatic BP in the metformin group compared to placebo, suggesting a potential adverse effect on cardiovascular autonomic function.
Mechanistic Insights
Renal Epithelial Sodium Channel Regulation
Metformin has been shown to alleviate diabetes-associated hypertension by attenuating the renal epithelial sodium channel (ENaC). This mechanism involves reducing renal cathepsin B expression, which in turn decreases sodium retention and helps control hypertension in diabetic nephropathy.
Postprandial Blood Pressure Regulation
Metformin also appears to modulate the cardiovascular response to oral glucose in T2DM patients, attenuating the postprandial fall in BP. This effect is associated with increased glucagon-like peptide-1 (GLP-1) secretion and delayed gastric emptying, contributing to its favorable cardiovascular profile.
Meta-Analyses and Systematic Reviews
Effects on Blood Pressure and Lipid Profile
A systematic review and meta-analysis of randomized controlled trials found that metformin does not have a significant intrinsic effect on BP in patients with T2DM. However, it does reduce total and LDL cholesterol levels, which may indirectly benefit cardiovascular health.
Blood Pressure in Nondiabetic Patients
Another meta-analysis focusing on nondiabetic patients revealed that metformin significantly lowers systolic BP, particularly in individuals with impaired glucose tolerance or obesity. However, its effect on diastolic BP was not significant.
Cardiovascular Risk Profile in Obese Women
In a study involving obese, nondiabetic, hypertensive women, metformin treatment resulted in significant reductions in BP, left ventricular mass, and several metabolic parameters, suggesting an overall improvement in cardiovascular risk profile.
Conclusion
The evidence indicates that metformin does not cause high blood pressure. Instead, it may have beneficial effects on BP, particularly in specific populations such as those with salt-induced hypertension or obesity. However, its impact can vary depending on the context, and in some cases, it may adversely affect orthostatic BP recovery. Overall, metformin's role in BP regulation appears to be complex and multifaceted, warranting further research to fully understand its cardiovascular effects.
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