Analysis compared metformin to sulfonylureas
BARCELONA -- Even in patients with reduced kidney functioning, metformin may hold a heart benefit, researchers reported here.
Compared with new users of sulfonylureas, individuals with slight renal impairment starting on metformin had a 20% lower risk for a major adverse cardiovascular event or MACE (adjusted HR 0.80, 95% CI 0.75-0.86), according to Christianne Roumie, MD, MPH, of Vanderbilt University Medical Center in Nashville, and colleagues.
This equated nearly six fewer MACE events per 1,000 person-years among new metformin users versus those beginning on sulfonylureas.
Findings of the retrospective cohort study were presented at the European Association for the Study of Diabetes 2019 meeting and simultaneously published in JAMA.
"We knew from multiple studies conducted in the U.S. and Europe that metformin was safe to use in patients with reduced kidney function, but many key studies that were done comparing these medications excluded patients with reduced kidney function," Roumie explained to MedPage Today. Back in 2016, the FDA revised their safety warning on metformin, which was initially restricted for patients with serum creatinine levels of 1.5 mg/dL or greater for men or 1.4 mg/dL or greater for women, to instead be indicated for those with mild to moderate kidney disease.
"The current study provides important information for the practicing clinician," she continued. "Among patients with diabetes and reduced kidney function treatment with metformin compared with a sulfonylurea was associated with a lower risk of MACE. Metformin should be continued after reaching reduced kidney function."
Roumie also noted how these findings add to the "limited observational evidence for the beneficial association of metformin compared to sulfonylurea and cardiovascular outcomes among those who develop reduced kidney function."
The U.S. study looked at a cohort of Veterans Health Administration patients with new-onset type 2 diabetes followed for at least 2 years. Nearly 68,000 were prescribed monotherapy consisting of metformin, while around 29,000 were started on either glipizide (Glucotrol), glyburide (Diabeta, Glycron, Micronase), or glimepiride (Amaryl). At study entry, all patients were considered to have reduced kidney functioning defined as a serum creatinine level of 1.5 mg/dL for men or 1.4 mg/dL for women, or an eGFR less than 60 mL/min/1.73 m2. Adherence to medication was roughly 80% among the cohort.
MACE was a composite of hospitalization for acute myocardial infarction, ischemic or hemorrhagic stroke, transient ischemic attack, or cardiovascular death. This last component was the biggest contributor to the overall MACE risk reduction with metformin:
- CV death: aHR 0.70 (95% CI 0.63-0.78)
- CV hospitalization for AMI, stroke, or TIA: aHR 0.87 (95% 0.80-0.95)
In an accompanying editorial, Deborah Wexler, MD, MSc, of Massachusetts General Hospital in Boston, said these findings reinforce clinical practice recommendations of metformin as initial monotherapy "even as early chronic kidney disease develops."
However, when selecting the best therapy for patients, Wexler highlighted the need to clinicians to keep in mind a patient-centric approach to prescribing. "The adverse effect profile of sulfonylureas and their very low cost must be balanced against characteristics of other glucose-lowering medications as clinicians consider the best approach for an individual patient," she wrote.
Limitations of the study included the nearly exclusive male and overwhelmingly white cohort.
Roumie added that her group is continuing research in this area, looking at several clinical outcomes among patients with diabetes and compromised kidney function.
The study was funded by VA Clinical Science Research and Development.
Roumie reported receiving grants from the Veterans Health Administration, the Patient-Centered Outcomes Research Institute, and the Agency for Healthcare Research and Quality. Other study authors also reported disclosures.
Editorial author Wexler reported a relationship with Novo Nordisk.
Source Reference: Roumie C, et al "Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function" JAMA 2019; DOI: 10.1001/jama.2019.13206.
Source Reference: Wexler, D "Sulfonylureas and Cardiovascular Safety The Final Verdict?" JAMA 2019; DOI: 10.1001/jama.2019.14533.
Read the original article on Medpage Today: Metformin Monotherapy Benefits Heart Even in Early CKD