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Metformin vs. Sulfonylureas: Heart Failure Hospitalization

May 11, 2021
 
Editor: Steve Freed, R.PH., CDE

Author: Brenda Oppong, PharmD Candidate, LECOM School of Pharmacy

A retrospective cohort analyzed the association of two commonly prescribed medications, metformin and sulfonylureas, on heart failure outcomes in patients with reduced estimated glomerular filtration rate.

Sulfonylureas and metformin are two commonly prescribed medications for treating patients with type 2 diabetes (T2D). Sulfonylureas work by stimulating the release of insulin from the pancreas and are generally well tolerated. Metformin’s mechanism of action is to decrease hepatic glucose production and intestinal absorption of glucose and increase insulin sensitivity. Although both medications are highly effective for treating T2D, every drug comes with its side effects. A retrospective cohort analyzed the association of metformin and sulfonylureas on heart failure outcomes in patients with reduced estimated glomerular filtration rate. 

 

Impaired kidney function and heart failure are secondary complications that often develop in a patient with T2D. It is recommended to reduce the use of metformin in patients with diabetes and reduced kidney function; therefore, there is limited research and understanding of metformin’s impact on heart failure outcomes among those patients, which remains poorly understood. The most common cause of hospitalization among veterans and patients with Medicare is heart failure. The study combined data from Veterans Health Administration (VHA), Medicare, Medicaid, and the National Death Index files. The participants were veterans, primarily white males, aged 18 years and older, who had an encounter or prescriptions filled at least once every 365 days with VHA care for two or more years before the cohort entry. The patients selected were newly diagnosed with T2D and new metformin users, glipizide, glyburide, or glimepiride, and did no fill glucose-lowering drugs in the 180 days before the first fill. Patients experiencing a decline in kidney function were selected and required to persist with their initial monotherapy with no medication gaps for more than 180 days. The start of follow-up and index date was to reach either eGFR of <60 mL/min per 1.73m2 or serum creatine level of ≥1.5 mg/dL for men or ≥1.4 mg/dL for women. The cohort entry and index date were between January 1, 2002, and December 30, 2015, with follow-up through December 31, 2016. The exclusion criteria included patients who switched or added glucose-lowering medication before or at the kidney threshold or had a single episode of dialysis, organ transplant, or enrollment in hospice care at or within the two years before reaching the reduced kidney function threshold. The patients continued taking metformin and sulfonylureas after reaching the reduced kidney thresholds. 

The primary outcomes were hospitalization with a primary discharge diagnosis of heart disease. Heart disease included cardiomyopathy, heart failure, or hypertensive heart disease with heart failure. The admission date was the outcome date. The primary analysis compared the cause-specific hazard of heart failure hospitalizations between sulfonylurea and metformin and accounted for medication nonpersistence and all-cause death. The type of heart failure that was associated with hospitalization was separated into ejection fraction (E.F.) (reduced<40%, midrange 40%–49%, and preserved ≥50%, or unknown E.F.). Any other type of heart failure was combined and called “other heart failure hospitalization.”

The weighted cohort included 24,805 sulfonylurea users and 24 685 metformin users with reduced kidney function, the median age of 70, and an estimated glomerular filtration rate (eGFR) of 55.8 mL/min per 1.73 m2. The prevalence of cardiovascular disease (31.6%) and underlying congestive heart failure (12.15%) between metformin and sulfonylurea were equally distributed. The median follow-up for patients taking metformin was 1.03 years verse 1.17 years for sulfonylurea. 775 heart failure hospitalization events occurred among patients taking metformin (16.9; 95% CI, 15.8–18.1 per 1000 person) with reduced kidney function and 992 events among patients taking sulfonylurea (20.7; 95% CI, 19.5–22.0 per 1000 person). The cause-specific hazard ratio (H.R.) for heart failure hospitalization among metformin was 0.85 (95% CI, 0.78–0.93) compared with sulfonylurea users. Over a period of five years, the probability of heart failure hospitalization at one year was 1.6% for metformin and 2.0% sulfonylurea and 3.0% versus 3.8% at five years. 44% of metformin users did not have an echocardiogram, 28% had reduced E.F., 9% had midrange E.F., and 19% preserved E.F. Among sulfonylurea users, 45% did not have an echocardiogram, 31% were categorized as reduced E.F., 9% as midrange E.F. and 19% as preserved E.F. Heart failure hospitalization with reduced E.F. (hazard ratio, 0.79; 95% CI, 0.67–0.93) and unknown E.F. (hazard ratio, 0.84; 95% CI 0.74–96) was considerably lower in metformin than the sulfonylurea users. 

The results concluded that patients with T2D and reduced kidney function on persistent metformin, compared with sulfonylurea use, was associated with reduced heart failure hospitalization. 

Practice Pearls: 

  • There is limited research and understanding of metformins impact on heart failure outcomes among patients with T2D and reduced kidney function. 
  • Continued metformin use was associated with reduced heart failure hospitalization. 

 

Richardson, Tadarro L Jr et al. Hospitalization for Heart Failure Among Patients With Diabetes Mellitus and Reduced Kidney Function Treated With Metformin Versus Sulfonylureas: A Retrospective Cohort Study. Journal of the American Heart Association; June 2021. 

 

Author: Brenda Oppong, PharmD Candidate, LECOM School of Pharmacy