Pharmacists and SGLT2 Inhibitors are the “Superheroes” Who Treat CKM Syndrome

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and pharmacists are the “superheroes” when managing cardiovascular-kidney-metabolic (CKM) syndrome, according to moderators of a 2025 ASHP Midyear Clinical Meeting Exhibition presentation, “And the Beat Goes On: Improving Heart Failure and Chronic Kidney Disease Outcomes with SGLT2 Inhibitors.”

The moderators, Leo F. Buckley, PharmD, MPH, BCCP, assistant professor in the Division of Cardiology at the University of Texas Southwestern Medical Center, Dallas, Texas, and Susan Cornell, PharmD, CDCES, FAPhA, FADCES, diabetes care and education specialist and consultant at Bolingbrook Christian Health Center and Will Grundy Medical Clinic in Illinois, noted these agents’ benefits extend beyond glucose control to reduce cardiovascular events and slow chronic kidney disease (CKD) progression in patients with and without diabetes.¹

What is CKM Syndrome?

The American Heart Association (AHA) defines CKM syndrome as a systemic disorder characterized by pathophysiologic interactions among metabolic risk factors (eg, obesity, diabetes, hypertension), CKD, and the cardiovascular system. These interactions ultimately lead to multiorgan dysfunction and result in a high rate of adverse cardiovascular outcomes. Additionally, the AHA packaged these overlapping conditions into a “formal syndrome” to provide a common framework for discussion among health care professionals and patients and to drive research into patient care.²

CKM syndrome is fundamentally linked by a reciprocal relationship between its core components. As an example, patients who have heart failure are at a 4 times higher risk of developing CKD. Conversely, the risk of developing heart failure increases as kidney function worsens because estimated glomerular filtration rate (eGFR) declines and urine albumin-to-creatinine ratio (UACR) rises. Buckley explained that this interconnectedness emphasizes that if a person has 1 condition, they are likely to develop the others if they are not already present.^1,2

The Impact of CKD on CKM Syndrome

CKD is one of the main core components of CKM syndrome. Not only does CKD increase one’s risk of heart failure, but the opposite is also true—those who have heart failure are at a 4.5 times higher risk of developing kidney failure compared with someone who does not have heart failure. The speakers explained that the kidney has 2 “arch enemies,” high blood pressure and high sugar. By lowering these 2 factors, the kidney is in a “happy state.”¹

The Use of SGLT-2 Inhibitors in CKM Syndrome

SGLT2 inhibitors, which are often considered in the first-line treatment setting, have emerged as a key disease-modifying therapy to prevent the progression of disease, particularly among those with CKD. Not only are these drugs effective in the treatment of CKD, but they address the other components or factors of CKM syndrome, such as heart failure and diabetes.^1,3

The decision to use an SGLT2 inhibitor is often based on eGFR and UACR, Cornell explained. In patients with CKD, an SGLT2 inhibitor is indicated if the patient is in the eGFR range of 25 to 90 mL/min/1.73 m² and has a UACR of 200 mg/g or greater. For those with reduced eGFR without albuminuria, an SGLT2 inhibitor is indicated even if albuminuria is not required, provided that the eGFR is in the range of 20 to 45 mL/min/1.73 m². The minimum eGFR requirements for initiation or continuation are the following¹:

• initiation is generally not recommended if eGFR is < 20 mL/min/1.73 m² for empagliflozin (Jardiance; Boehringer Ingelheim, Eli Lilly & Co);
• eGFR must be greater than 25 mL/min/1.73 m² for dapagliflozin (Farxiga; AstraZeneca) and sotagliflozin (Inpefa; Lexicon Pharmaceuticals);
• and a minimum eGFR for initiation is greater than 30 mL/min/1.73 m² for canagliflozin (Invokana; Janssen Pharmaceuticals).

The speakers emphasized that not all SGLT2 inhibitors are made alike and their approved indications differ. Specifically, dapagliflozin and empagliflozin, along with sotagliflozin, are approved for both reduced and preserved ejection fraction in heart failure, and canagliflozin, dapagliflozin, and empagliflozin are approved for CKD. Importantly, it is estimated that up to a quarter of adult patients with CKD in the US have an indication for an SGLT2 inhibitor; therefore, the potential impact of widespread use is large, with the number of heart failure and cardiovascular death events among people with CKD and albuminuria estimated to be nearly cut in half annually.¹

SGLT2 inhibitors lower the renal threshold for glucose excretion. Buckley and Cornell explained that, normally, the kidneys start excreting sugar when blood glucose reaches 180 mg/dL. SGLT2 inhibitors are able to lower this threshold, causing sugar to be excreted at a lower level (140 mg/dL), which means the patient urinates more glucose and water. This provides a diuretic effect by causing the loss of water, sodium, and electrolytes. By reducing inflammation and oxidative stress, improving signaling to decrease myocardial stiffness, and reducing renal dysfunction, SGLT2 inhibitors improve both kidney and cardiovascular function. The overall effect includes reducing glucose toxicity from the kidney, which subsequently improves kidney function by lowering blood pressure and sugar.¹

Social Determinants of Health and Treating CKM Syndrome: The Pharmacist’s Role

Furthermore, the speakers emphasize the crucial influence of social determinants of health (SDOH) and lifestyle modifications as foundational elements alongside guideline-directed medical therapy. SDOH are a critical component of providing person-centered, individualized care for those with CKM syndrome and are significant risk factors for adverse outcomes.¹

“[Pharmacists] are that superhero to pull all these guidelines together and work with [the] patient as a whole, but all of that does no good if the patient can't get to us. And this is where SDOH comes in, and we're seeing more and more of it,” Cornell said.¹

Different SDOH include financial barriers, food insecurity and/or housing Insecurity, health insurance status or access, environmental and neighborhood factors, as well as other Disparities, such as race, ethnicity, preferred language for health discussions, and disabilities that must be assessed to address disparities in care and outcomes.¹

The speakers urged that pharmacists and health care professionals must incorporate methods for providing holistic, person-centered care through addressing individualized SDOH barriers. Finally, screening patients with CKM syndrome for SDOH can allow providers to better address the individual patient and their needs.¹

REFERENCES

1. Buckley LF, Cornell SC. And the Beat Goes On: Improving Heart Failure and Chronic Kidney Disease Outcomes with SGLT2 Inhibitors. Presented at: 2025 ASHP Midyear Clinical Meeting Exhibition. December 7–10; Las Vegas, Nevada.

2. Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20). Published online October 9, 2023. doi:10.1161/CIR.0000000000001184

3. Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations. Kidney Int Rep. 2022;7(7):1463-1476. Published 2022 May 5. doi:10.1016/j.ekir.2022.04.094