Antihyperglycemic Medication Use Among Medicare Beneficiaries With Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease

Abstract

Background: Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood.

Methods and results: Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m(2). Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71-83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5-35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2-7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m(2), 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran-Mantel-Haenszel row-mean score test P=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (P<0.001).

Conclusions: Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a thiazolidinedione, despite known concerns regarding HF. More research regarding safety and efficacy of various AHMs among HF patients is needed.

Keywords: chronic kidney disease diabetes mellitus; glomerular filtration rate; heart failure; insulin.

Figure 1. Overall Semi-Annual AHM Use

This graph describes overall use of AHMs on a semi-annual basis among all patients included in this study. Arrowheads represent, in chronological order from left to right, the publication of DREAM trial (DREAM=Diabetes REduction Assessment with ramipril and rosiglitazone Medication Trial) showing higher numerical risk of heart failure by rosiglitazone, publication of meta-analysis suggesting HF risk by thiazolidinediones, and date of FDA black box warning for thiazolidinediones for heart failure^{, ,} . Information regarding potential HF risk for DPP4-inhibitors was not available until late 2013. Cochran-Mantel-Haenszel Row Mean Score Test for Trend: metformin p=0.433, sulfonylurea p<0.001, meglitinide p=0.024, GLP-1 agonist p=0.035, DPP-4 inhibitor p<0.001, alpha-glucosidase inhibitor p=0.017, thiazolidinedione p<0.001, insulin p=0.113, amylin analog p=0.280. Abbreviations: AHM=antihyperglycemic medication, DPP4=dipeptidyl-peptidase 4 inhibitor, GLP-1 agonist=glucagon like peptide 1 agonist

Figure 2

Panel A: Use of AHMs Among Patients with eGFR<30mL/min/1.73m². Use of renal contraindicated AHM was 35.4% overall, with a trend towards lower renal contraindicated use over time (Cochran-Mantel-Haenszel row-mean score test p=0.048). Panel B: Overall Use of AHMs Among Patients with eGFR<30mL/min/1.73m². Cochran-Mantel-Haenszel row-mean score tests: metformin p=0.542, DPP-4 inhibitors p<0.001, thiazolidinediones p<0.001, sulfonylurea p=0.005, meglitinide p=0.381. Arrowheads represent, in chronological order from left to right, the publication of DREAM trial showing higher numerical risk of heart failure by rosiglitazone, publication of meta-analysis suggesting HF risk by thiazolidinediones, and date of FDA black box warning for thiazolidinediones for heart failure^{, ,} . Information regarding potential HF risk for DPP4-inhibitors was not available until late 2013. Abbreviations: AHM=antihyperglycemic medication, eGFR=estimated glomerular filtration rate, DPP4=dipeptidyl-peptidase 4 inhibitor

Figure 2

Panel A: Use of AHMs Among Patients with eGFR<30mL/min/1.73m². Use of renal contraindicated AHM was 35.4% overall, with a trend towards lower renal contraindicated use over time (Cochran-Mantel-Haenszel row-mean score test p=0.048). Panel B: Overall Use of AHMs Among Patients with eGFR<30mL/min/1.73m². Cochran-Mantel-Haenszel row-mean score tests: metformin p=0.542, DPP-4 inhibitors p<0.001, thiazolidinediones p<0.001, sulfonylurea p=0.005, meglitinide p=0.381. Arrowheads represent, in chronological order from left to right, the publication of DREAM trial showing higher numerical risk of heart failure by rosiglitazone, publication of meta-analysis suggesting HF risk by thiazolidinediones, and date of FDA black box warning for thiazolidinediones for heart failure^{, ,} . Information regarding potential HF risk for DPP4-inhibitors was not available until late 2013. Abbreviations: AHM=antihyperglycemic medication, eGFR=estimated glomerular filtration rate, DPP4=dipeptidyl-peptidase 4 inhibitor