Why Can’t We Flozinate? Reflections on Our Inability to Optimally Prescribe SGLT2 Inhibitors to the Patients That Need Them Most

Dr. James Torain is a second-year nephrology fellow at Duke University Hospital. He currently has an interest in implementation of home dialysis modalities. Health disparities have been a particular interest of his since completing his medical degree at Meharry Medical College.  His fascination with the intricacies of renal physiology and CKD prevention developed during his residency at the University of Tennessee Health Science Center. Outside of medicine, Dr. Torain enjoys running, playing the drums, and speaking at local church health symposiums.

Dr. Matthew Sinclair @mattysincs is currently at Medical Instructor at Duke University School of Medicine and a faculty member at the Duke Clinical Research Institute in Durham, NC. His research focuses on reducing the progression of CKD among racial and ethnic minorities both by enhancing recognition of chronic kidney disease risk factors among individuals in the community and developing interventions to optimize evidence-based screening and therapy provision for patients with or at risk for CKD. Dr. Sinclair has also been very proud to serve as a member of the NKF Health Equity Advisory Committee since 2023. In addition to his research and advocacy work, Dr. Sinclair greatly values his time working with patients as a nephrologist at both Duke University Hospital and the Durham Veterans Affairs Medical Center. When not at work, Dr. Sinclair enjoys traveling and spending time with his wife and two young sons.

In March of 2013, canagliflozin became the first sodium glucose cotransporter-2 (SGLT2) inhibitor approved to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). In the decade since, numerous cardiovascular outcome trials (CVOTs) examined multiple SGLT2 inhibitors, all of which noted impressive reductions in adverse cardiovascular and kidney outcomes. In 2019, the CREDENCE trial became the first CVOT to specifically examine and note a lower risk of kidney failure and cardiovascular events in patients with both T2DM and chronic kidney disease (CKD). Since then, multiple other trials have noted similar results, even in patients with advanced CKD with and without T2DM, solidifying this medication class as a mainstay of treatment for all patients with CKD. In fact, the recent KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD recommends SGLT2 inhibitors as first-line therapy.

So, these “miracle drugs” are being prescribed frequently and to those patients who need them most, right? Unfortunately, this is not the case. In a recently published study examining prescribing of SGLT2 inhibitors through 2019 among insured patients with T2DM and CKD, initiation rate of SGLT2 inhibitors was only 2.5%.  Perhaps this under-prescribing could be attributed to cost, as these medications are often quite expensive for patients, even those with insurance. Therefore, examining prescribing in a system where price isn’t an issue would be ideal to eliminate cost as a reason for under-prescribing; enter the Veterans Affairs (VA) healthcare system. The VA system offers heavily discounted or free medications to patients, reducing the influence of cost as a factor. This allows us to control for the cost of drugs and evaluate other factors that may cause lack of optimal prescribing of SGLT2 inhibitors.  In 2022, a JAMA trial was published that examined prescribing of SGLT2 inhibitors among adults with T2DM in the VA system from January 2019 through December 2020, and unfortunately, prescribing rates remained poor, with only 10.7% of eligible patients receiving an SGLT2 inhibitor. Furthermore, racial and ethnic minority individuals (most prominently Black and Hispanic patients) were even less likely to receive these medications.

In the recently published July 2023 issue of AJKD, a study from L. Parker Gregg and colleagues expanded on the previously described JAMA article to examine prescribing among US veterans with comorbid T2DM, CKD, and atherosclerotic cardiovascular disease, who had at last one primary care visit in 2020. The investigators examined the associations of race and sex with prescribing, in addition to facility level variation. Notably, Hispanic ethnicity was not evaluated as a predictor for prescribing in this study. Like the JAMA study, SGLT2 inhibitor prescribing overall was poor, with only 11.5% of veterans prescribed an SGLT2 inhibitor. There was a profound racial discrepancy in prescribing, with Black Patients being about 13% less likely to receive an SGLT2 inhibitor compared to White patients. Furthermore, women were over 40% less likely to receive an SGLT2 inhibitor compared to men. In terms of facility level variation, there was a residual 58% variation in treatment with SGLT2 inhibitors among two similar patients and two random facilities, indicating large variation of prescribing.

This study also thoroughly evaluated race and sex disparities in prescribing among subgroups. Overall, as comorbidities (ie, CKD, heart failure, and T2DM) became more advanced or less controlled, disparities between Black and White patients were attenuated. However, among patients with less advanced disease who would still benefit from an SGLT2 inhibitor, Black patients were prescribed the medication significantly less. In academic medical centers, there was no difference in prescribing between Black and White patients, but Black patients were less likely to be prescribed SGLT2 inhibitors at community medical centers. As far as sex disparities, nearly all subgroups of women had lower prescribing than men.

There are multiple possible reasons for the reasons for the findings in the study. Unconscious bias likely plays a role, as it seems providers recognize the value in prescribing SGLT2 inhibitors to Black patients more once their disease and comorbidities are advanced, as opposed to earlier on, when these drugs have just as much if not more benefit. Additionally, it’s likely that providers associated with academic medical centers may be more updated with recent evidence that supports prescribing of the SGLT2 inhibitors, compared to their counterparts working in community settings. It should also be noted that trainees at teaching (ie. academic) facilities are being precepted, meaning that there is an active review process for patients that they see. Having multiple providers involved in the decision-making process may lead to improved prescribing. As far as the sex disparities seen in the trial, it’s important to note that the VA population is predominantly male, including >98% of patients in this study. That being said, the lack of prescribing in women is notable, and may be partially attributable to the concern for the SGLT2 inhibitors to cause urinary tract infections, specifically in peri- and post-menopausal women. This concern may be exacerbated by the fact that these female patients are being seen by providers who may not used to be seeing many female patients, and hence may be more hesitant to prescribe these medications that those providers in the community setting.

In conclusion, providers need to do a better job of prescribing SGLT2 inhibitors to all patients. It is especially concerning that racial and ethnic minority individuals, including Black and Hispanic patients, are being prescribed these medications at lower rates than their White brethren, when they are already at a higher risk of progressing to end stage kidney disease. We explored multiple factors that may be associated with reduced prescribing, some of which affect only patients in the VA or the civilian world, but most of which affect all patients:

Possible Reasons for Lack of SGLT2 inhibitor Prescribing In VA vs Civilian Systems. © Torain, Sinclair

Clearly, more studies are needed to better understand all reasons for lack of prescribing of these life-saving medications, so that we may do a better job of addressing the barriers to adequate prescribing and get these medications into the hands of the patients who need them most.

– Post prepared by James Torain and Matthew Sinclair @mattysincs


To view Gregg et al (subscription required)please visit AJKD.org.
Title: Predictors, Disparities, and Facility-Level Variation: SGLT2 Inhibitor Prescription Among US Veterans With CKD
Authors: L. Parker Gregg, David J. Ramsey, Julia M. Akeroyd, Shehrezade A. Jafry, Michael E. Matheny, Salim S. Virani, and Sankar D. Navaneethan
DOI: 10.1053/j.ajkd.2022.11.017



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