This meta-analysis reveals that Metformin can lower systolic BP by 5 and 3 mmHg in prediabetic and obese individuals. This finding is in accordance with the notion of insulin resistance being at the center of metabolic syndrome; manifestations of which are increased blood pressure, blood sugars and “abdominal” obesity. About 4,000 subjects from 28 studies were included in the meta-analysis.
Journal of Hypertension
Objective: To evaluate the effects of metformin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in nondiabetic patients.
Methods: In this meta-analysis, we systematically searched PubMed, Embase, and the Cochrane Library through March 2016, and randomized controlled trials assessing the effects of metformin treatment compared with placebo were included. Random-effects models were used to estimate pooled mean differences in SBP and DBP.
Results: 28 studies from 26 articles consisting of 4113 participants were included.
Pooled results showed that metformin had a significant effect on SBP (mean difference −1.98 mmHg; P = 0.02), but not on DBP (mean difference −0.67 mmHg; P = 0.22).
In subgroup analysis, we found that the effect of metformin on SBP was significant in patients with impaired glucose tolerance or obesity (BMI ≥30 kg/m2), with a mean reduction of 5.03 and 3.00 mmHg, respectively.
Significant heterogeneity was found for both SBP (I2 = 60.0%) and DBP (I2 = 45.4%). A sensitivity analysis indicated that the pooled effects of metformin on SBP and DBP were robust to systematically dropping each trial. Furthermore, no evidence of significant publication bias from funnel plots or Egger’s tests (P = 0.51 and 0.21 for SBP and DBP, respectively) was found.
This meta-analysis suggested that metformin could effectively lower SBP in nondiabetic patients, especially in those with impaired glucose tolerance or obesity.
Editoral on the subject:
The blood pressure effects of metformin in nondiabetic subjects were evaluated in a recent meta-analysis. The meta-analysis included 4113 participants from 28 separate studies reported in 26 publications. The authors found that metformin lowered systolic BP an average of 2.0 mmHg across all studies. The effects of metformin on systolic BP were most clearly evident among individuals with impaired fasting glucose (−5.0 mmHg) and with obesity (−3.0 mmHg).
While mean diastolic BP value declined, the changes were not statistically significant in all subjects combined or in subgroup analyses. While there was evidence for heterogeneity between studies in metformin’s effects on systolic BP, exclusion of any single study did not materially alter the findings. Moreover, publication bias, assessed by funnel plots and Egger’s test, was not found.
A prior meta-analysis, which included 31 studies with 4570 subjects at risk for diabetes and 8267 patient years of observation, assessed the effects of metformin on multiple cardiovascular risk factors. In this report, metformin significantly lowered BMI 5.3%, fasting glucose 4.5%, fasting insulin 14.4%, calculated insulin resistance 22.6%, triglycerides 5.3%, and LDL cholesterol 5.6%, while raising HDL cholesterol 5.0%.
Metformin is widely recommended for the initial treatment of type 2 diabetes and reduces cardiovascular events in this at-risk population. Prevalent prediabetes has been increasing and was estimated to impact 38% of US adults in 2011–2012. While metformin has been recommended for reducing incident diabetes in patients with prediabetes by the American Diabetes Association since 2008, it is only prescribed to roughly 1 in 25 adults with prediabetes. As one potential barrier to wider use of metformin for diabetes prevention, the Food and Drug Administration (FDA) has not approved metformin for this indication. Under current regulations, metformin probably will not receive FDA approval for diabetes prevention, since the application must come from the original patent holder for a medication that is widely available as an inexpensive generic.
Prehypertension, which affects ∼70 million US adults, is associated with doubling of risk for incident diabetes. The impact of prehypertension is diminished after adjusting for body mass index and abnormalities of glucose metabolism and insulin action. This constellation of interrelated risk factors for diabetes and cardiovascular disease, if anything, strengthens the rationale for using metformin, which can favorably impact each of these risk components.
The recent paper by Zhou et al showing that metformin lowers systolic BP, especially in patients who are prediabetic or obese, provides additional evidence for its use in a large population of individuals at high risk for incident diabetes, who often have multiple cardiovascular risk factors, including elevated BP. Despite the established benefits of metformin and the American Diabetes Association recommendation for its use in prediabetes to reduce incident diabetes, this drug is rarely prescribed to this at-risk population. Thus, there is a large gap between the evidence on the beneficial effects of metformin on glucose and lipid metabolism as well as BP and its very limited use in the many millions of patients with prediabetes, many of whom have prehypertension.
Attaining appropriate use of metformin may require a multifactorial approach that could include the following: (1) educational initiatives by professional societies aimed at clinicians and the public, (2) development of quality metrics that quantify clinician and health system performance on appropriate use of metformin for prevention of diabetes, and (iii) policy changes by the FDA that facilitates the approval of new indications for old medications, for example, metformin, which are well advanced into their generic years. Pragmatic trials focused primarily on existing and regularly updated clinical and claims databases to document the efficacy and safety of metformin for preventing diabetes, improving multiple risk factors, and reducing cardiovascular events would be invaluable in sustaining and growing appropriate use given the epidemic of obesity and cardiometabolic risk.