Metformin may have CV benefits in CKD patients with MetS

Metformin may improve vascular function in chronic kidney disease (CKD) patients with metabolic syndrome (MetS), according to a study presented at ASN Kidney Week 2020.

­“[Patients with CKD] have unacceptably high cardiovascular (CV) mortality rate that is not entirely explained by traditional CV risk factors. Thus, there is a current focus on non-traditional risk factors in CKD, such as insulin resistance, systemic inflammation, oxidative stress, obesity, and endothelial dysfunction,” said Dr Everly Ramos from the Vanderbilt University Medical Center, Nashville, Tennessee, US, who presented the findings.

“[Our findings show that] treatment with metformin improved brachial artery flow mediated dilation (FMD) [and] reduced lectin-adiponectin ratio (LAR),” said Ramos.

After 16 weeks of treatment, there was a significant increase in brachial artery FMD among patients on metformin vs those on placebo (p=0.03). [ASN Kidney Week 2020, abstract FR-OR20]

For the secondary outcome, compared with placebo use, metformin use led to a significant reduction in LAR (p=0.04) and leptin (p=0.003), but not adiponectin (p=0.83), after 16 weeks of treatment.

Insulin resistance is common in patients with CKD and is predictive of CV and all-cause mortality in nondiabetic patients with end-stage renal disease. [Clin J Am Soc Nephrol 2012;7:588-594; J Am Soc Nephrol 2002;13:1894-1900] “[LAR is] a practical and accurate index of insulin resistance,” said Ramos, adding that a higher LAR ratio is associated with higher insulin resistance. [Clin J Am Soc Nephrol 2011;6:767-774] Taking these points together, the reduced LAR observed in the study may signal reduced insulin resistance and consequently, a reduced CV risk in this patient group, she added.

However, metformin use was not associated with any benefit in the other subclinical markers of CV disease such as aortic pulse wave velocity (p=0.84) and carotid intima media thickness (p=0.74 and 0.44 for the right and left internal carotid arteries, respectively).

Ramos and colleagues used a sample of 60 obese/overweight patients (median age 66 years, 80 percent male) with moderate CKD to determine whether metformin will improve subclinical CV disease markers compared with placebo. Participants were randomized 1:1 to receive either metformin or placebo for 16 weeks.

Taken together, the findings suggest that, apart from its antihyperglycaemic effect, metformin may also render CV benefits in patients with MetS or prediabetes, said Ramos.

She added that preclinical evidence reflecting the anti-inflammatory effects of metformin helps elucidate the role of metformin in the prevention and/or treatment of vascular injury, atherosclerosis, and insulin resistance. [Diabetes 2015;64:2028-2041; Diabetes 2015;64:1907-1909]

Ramos called for longer and larger trials to ascertain the vascular benefits of metformin in this patient setting.