Sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i), or gliflozins, block SGLT2 cotransporters in the proximal tubules and reduce renal glucose and sodium reabsorption.1 Reduced reabsorption of sodium results in natriuresis, which, through tubuloglomerular feedback, causes a reduction of intraglomerular pressure. SGLT2i have been shown to not only slow kidney progression in patients with chronic kidney disease regardless of diabetes status, but also improve glucose control, reduce the risk of heart failure, and reduce blood pressure, and they do so in a cost-effective manner.2
The use of SGLT2i has been limited despite approval in the United States since 2013 (canagliflozin). One important factor, which research suggests might be a myth, is that underutilization of SGLT2i therapy is due to their high cost or high copayments.
Two recent studies have reported on utilization of SGLT2i where cost was not a factor, namely the US Department of Veterans Affairs (VA), where prescriptions are free. The first study by Mahtta et al looked at SGLT2i use in 537,980 patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM) in 130 VA facilities.3 They reported that approximately 11% of patients were on SGLT2i therapy. Surprisingly, among individuals with an estimated glomerular filtration rate of >30 mL/min/1.73m2, only 14% of individuals were being treated with an SGLT2i.
The second study was presented by Hussain and colleagues on March 3, 2023, at the American College of Cardiology meeting in New Orleans.4 The authors evaluated 105,799 patients with ASCVD, heart failure, and T2DM across 130 VA facilities; 14.6% of those patients received SGLT2i. There was significant facility-level variability in both analyses, suggesting that practice patterns may be an important factor.
Some argue that underutilization of SGLT2i is not surprising because adoption of novel therapies often takes several years. This “therapeutic inertia,”5,6 defined as continuing an older clinical treatment despite less efficacy and failing to start a new medication that has proven more effective,6 has been ascribed to both patient and provider factors.7 For patients, old habits die hard, and they become comfortable with an older medication. Changing medications can sometimes be confusing and adds to pill burden. In the case of SGLT2i, a conversation about the risk of genital infections and the importance of genital hygiene could be viewed as awkward.
Providers, on the other hand, may have inertia because of the work involved in starting and up-titrating the SGLT2i. Another common refrain could be that “there isn’t enough time in the day” to complete all the paperwork required to get the patient’s insurance to approve initiation of SGLT2i. In addition to these factors, I’ve also wondered whether there is confusion among providers about who owns the therapy—the diabetologist, the cardiologist, or the nephrologist?
Things could change over the next 2 years as the main product patents on SGLT2 inhibitors expire between 2023 and 2025. With generics on the market, the price of SGLT2i is likely to fall dramatically. Still, reducing the price could have other inadvertent effects. With less revenue from SGLT2i, pharma may decide to spend money on the promotion, education, and research of other emerging products. Lack of financial incentives may also influence prescribing patterns.8 The VA analyses point to considerable practice-level variability and suggest that some providers are reluctant, perhaps because of inertia, to use SGLT2i. Here, education and guideline-directed care are likely to be key. The American Diabetes Association and Kidney Disease: Improving Global Outcomes, among other organizations, have published guidelines, which should make a difference.
The bottom line is that we should be disappointed that 10 years after the first approval of SGLT2i therapy, less than 15% of patients are receiving treatment with them. These agents have been demonstrated to reduce progression of kidney disease and delay end-stage kidney disease. They have clear cardioprotective benefits. We all need to pull up our socks and start using them.
- Vallon V, Verma S. Effects of SGLT2 inhibitors on kidney and cardiovascular function. Annu Rev Physiol. 2021;83:503-528. doi:10.1146/annurev-physiol-031620-095920
- McEwan P, Foos V, Martin B, Chen J, Evans M. Estimating the value of SGLT2 inhibitors within the context of contemporary guidelines and totality of evidence. Diabetes Obes Metab. 2023. doi:10.1111/dom.15040
- Mahtta D, Ramsey DJ, Lee MT, et al. Utilization rates of SGLT2 inhibitors and GLP-1 receptor agonists and their facility-level variation among patients with atherosclerotic cardiovascular disease and type 2 diabetes: insights from the Department of Veterans Affairs. Diabetes Care. 2022;45(2):372-380. doi:10.2337/dc21-1815
- Hussain A, Ramsey D, Mahtta D, et al. Utilization rates of SGLT2 inhibitors and their facility-level variation among patients with type 2 diabetes (T2DM), heart failure, (HF) and atherosclerotic cardiovascular disease (ASCVD): insights from the Department of Veteran Affairs (VA). J Am Coll Cardiol. 2023;81(8_Supplement):1645. doi:10.1016/S0735-1097(23)02089-2
- Okemah J, Peng J, Quiñones M. Addressing clinical inertia in type 2 diabetes mellitus: a review. Adv Ther. 2018;35(11):1735-1745. doi:10.1007/s12325-018-0819-5
- Steinman MA, Landefeld CS. Overcoming inertia to improve medication use and deprescribing. JAMA. 2018;320(18):1867-1869. doi:10.1001/jama.2018.16473
- Bergethon KE, Wasfy JH. Increasing the adoption and diffusion of a novel pharmacological therapy that is both mortality reducing and cost-effective. J Am Heart Assoc. 2019;8(3):e011783. doi:10.1161/JAHA.118.011783
- Bergethon KE, Blumenthal DM. The interplay between financial incentives, institutional culture, and physician behavior: an incompletely understood relationship worth elucidating. J Hosp Med. 2019;14(1):60-62. doi:10.12788/jhm.3098