L. Parker Gregg, MD, MSCS, Investigator at Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey VAMC
HOUSTON — Discontinuation of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA) is common but is associated with harmful outcomes in adults with chronic kidney disease (CKD), according to a recent study.
The study published in the Journal of the American Society of Nephrology evaluated the rates of discontinuation of SGLT2 inhibitors and GLP-1 RAs in patients with chronic kidney disease, factors associated with treatment discontinuation and associations of treatment discontinuation with death and cardiovascular events because little is known.1
Study authors are affiliated with Baylor College of Medicine and Michael E. DeBakey VAMC in Houston and VA Tennessee Valley Healthcare System and Vanderbilt University Medical Center in Nashville, TN.
In patients with concomitant chronic kidney disease and Type 2 diabetes mellitus, “current guidelines highlight the importance of prescribing medications with cardiovascular and kidney protective effects, including angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB), SGLT2 inhibitors and GLP-1 RAs. Strong evidence supports the cardiovascular and kidney protective effects of SGLT2 inhibitors and GLP-1 RAs, so it’s vital to maximize treatment utilization to improve long-term patient outcomes,” the study authors explained.
They decried the underuse of medications with cardiovascular and kidney protective effects have been underutilized in CKD patients, however.
Treatment discontinuation is a “strong contributor to ACEi/ARB underutilization and is associated with a higher risk of cardiovascular events, end-stage kidney
disease and death. Understanding SGLT2 inhibitor and GLP-1 RA discontinuation patterns and associations of discontinuation with outcomes is necessary to improve treatment re-initiation rates,” the researchers suggested.
The study team identified adults with chronic kidney disease stages 3-4 from 2005 to 2022 in the VAHS. Patients with an incident prescription for SGLT2 inhibitors or GLP-1 RAs were included, with the first fill date considered the index date. The researchers analyzed factors associated with time to first treatment discontinuation, which is defined as an interruption in SGLT2 inhibitor or GLP-1 RA prescription for 90 days. They assessed associations of discontinuation 90–179 days and 180 days or more with death, myocardial infarction, coronary revascularization, hospitalization for heart failure and ischemic stroke.
“Among veterans with chronic kidney disease (CKD) stages 3-4 who were prescribed an SGLT2 inhibitor and/or a GLP-1 RA, discontinuation of these agents of at least 90 days was common, occurring in 37% of SGLT2 inhibitor users and 47% of GLP-1 RA users,” lead author L. Parker Gregg, MD, MSCS, an investigator at the Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VAMC, told U.S. Medicine. “Discontinuation of both agents was more common among Black and Hispanic veterans and patients with cerebrovascular disease, peripheral vascular disease or ischemic heart disease.”
Gregg, who also is an assistant professor in the Section of Nephrology at Baylor College of Medicine in Houston, added, “Women and patients with more advanced CKD were also more likely to have their SGLT2 inhibitor discontinued. SGLT2 inhibitor discontinuation was associated with death and heart failure hospitalization, while GLP-1 RA discontinuation was associated with death, myocardial infarction, heart failure hospitalization and ischemic stroke.”
Of the 96,345 patients who received an SGLT2 inhibitor and the 60,020 patients who received a GLP-1 RA, the study found that “at least one discontinuation occurred in 35,953 (37%) of SGLT2 inhibitor users and 28,407 (47%) of GLP-1 RA users. SGLT2 inhibitor users were 24% Black, 71% white, 71% age 70 and older, and 84% with chronic kidney disease stage 3a. GLP-1 RA users were 20% Black, 75% white, 63% age 70 and older, and 81% with chronic kidney disease stage 3a. Black race, Hispanic ethnicity, cerebrovascular disease, peripheral vascular disease and ischemic heart disease were associated with discontinuation of both drug classes,” according to the study.
Frequently Discontinued
“These important risk-reducing medicines are frequently discontinued in patients with kidney diseases, and discontinuation was associated with harmful cardiovascular outcomes,” Gregg said. “The reasons for discontinuation were not included in this study, but these will be important for us to learn more about how to guide treatment re-initiation.”
She pointed out that, in previous studies, the researchers showed that “both SGLT2 inhibitors and GLP-1 RAs are underprescribed to patients with chronic kidney disease who had multiple indications for use.”
“In this analysis we sought to quantify treatment discontinuation of SGLT2 inhibitors and GLP-1 RAs, identify factors associated with treatment discontinuation, and determine if discontinuation was associated with cardiovascular events and death,” Gregg said. “The veteran population is ideal to study this question because patients who receive care in the Veterans Health Administration have better access to receiving these medicines, primarily due to lower out-of-pocket cost. This work suggests that interventions targeting re-initiation of treatment in appropriate patients may help decrease total underutilization of these agents and potentially reduce cardiovascular outcomes.”
For healthcare professionals who are treating veteran patients with chronic kidney disease, she noted that “patients with kidney diseases may have their SGLT2 inhibitor or GLP-1 RA discontinued for a variety of reasons, and some will merit subsequent treatment re-initiation.”
“Understanding the reason for discontinuation and resuming treatment in appropriate patients could have a significant positive impact on cardiovascular health,” Gregg suggested.
- Gregg LP, Richardson PA, Nambi V, Petersen LA, Matheny ME, Virani SS, Navaneethan SD. Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Discontinuation in Patients with CKD. J Am Soc Nephrol. 2024 Aug 26. doi: 10.1681/ASN.0000000000000477. Epub ahead of print. PMID: 39186372.