GLP-1s, SGLT2 Inhibitors Reduce Progression of CKD

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In a session presented at the 2024 Heart in Diabetes Conference, Matthew Weir, MD, discussed the potential benefits of GLP-1s and SGLT2 inhibitors for improved chronic kidney disease and cardiovascular outcomes.

Despite limited data on outcomes for patients with glomerular filtration rates (GFR) and urine albumin-creatinine ratios (uACR) of under 30, researchers reported consistent benefits of glucagon-like peptide-1 receptor agonists (GLP-1s) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of chronic kidney disease (CKD) and cardiovascular (CV) complications.

Kidney disease is diagnosed using an estimated GFR test. According to Matthew Weir, MD, advanced CKD is diagnosed when a patient’s GFR is below 30. The lower the GFR, the closer a patient’s kidney is to failing.1,2

“The main issue with available data is the absence of clear data, because many of these people in large part either have been included because of low GFR or excluded because they have no microalbuminuria and to find people that have both is problematic,” said Weir during a presentation at the 2024 Heart in Diabetes Conference.2

Key Takeaways

  • In a study presented at the 2024 Heart in Diabetes conference, Matthew Weir, MD, explored a cohort of patients with low GFR and uACR scores and examined their CKD outcomes after GLP-1 and SGLT2 inhibitor treatment.
  • Researchers reported consistent benefits of GLP-1s and SGLT2 inhibitors for the treatment of CKD and cardiovascular complications.

Microalbuminuria is when the albumin protein is detected in an individual’s urine, which indicates improper kidney functioning and can also mean kidney disease.3 Weir said it’s very uncommon for individuals to have a low GFR of under 30 but not have microalbuminuria.

To diagnose microalbuminuria, patients must complete a uACR test. Unlike GFR rates that diagnose CKD, uACR levels must be high in order to diagnose microalbuminuria; the higher the uACR, the higher risk patients have of microalbuminuria and other kidney complications.4

Kidney disease is diagnosed using an estimated GFR test—the lower the GFR, the closer a patient’s kidney is to failing. | image credit: Kiattisak / stock.adobe.com

Kidney disease is diagnosed using an estimated GFR test—the lower the GFR, the closer a patient’s kidney is to failing. | image credit: Kiattisak / stock.adobe.com

Because low GFR and high uACR rates ultimately go hand in hand regarding CKD, Weir wanted to explore the unlikely combination of low GFRs and low uACRs under 30. Using this unexplored cohort, he and colleagues analyzed the CKD outcomes of GLP-1s and SGLT2 inhibitors.

Weir approached this group by first analyzing CV outcome studies. “People with diabetes and kidney disease don't die from kidney disease, they die from cardiovascular disease,” he said.2 “Outcomes really need to look at both.”

Weir first explored the benefits of SGLT2 inhibitors for CKD outcomes.

“Start with the SGLT2 inhibitors first. There is abundant data from all of these different trials indicating that there is an advantage to the use of these drugs as part of our clinical regimen to delay progression of kidney disease,” continued Weir. He also said that, despite unavailable data featuring individuals with low uACRs and low GFRs, the benefits of SGLT2 medications are “very, very consistent.”2

He then explored the benefits of GLP-1s, such as semaglutide, and their benefits for treating type 2 diabetes (T2D), obesity, and most recently, CV outcomes. Since CKD can lead to death by CV complications, Weir also wanted to see how CV and CKD outcomes could be improved with the use of GLP-1s for patients with low GFR.

Despite only examining individuals with GFRs under 30, and not uACRs of under 30 as well, a study from Taiwan found a significant advantage of GLP-1s compared with dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of T2D and CKD. Researchers also found a significant improvement of all-cause mortality for low GFR individuals using GLP-1s.2

“The consistency I think is the key issue here. Whether you're looking at estimated GFR change or not, there's always an advantage to the therapy and this is very consistently seen whether you look overall 30 to 60 or 60,” said Weir when discussing GLP-1s.

Offering several examples from various studies, Weir presents data that explores the benefits of both GLP-1s and SGLT2 inhibitors. Despite issues in identifying the desired cohorts for each study, specifically individuals with low GFRs and uACRs, Weir maintains his recommendation of these therapies to treat CKD and improve CV outcomes.

“I would put into perspective for both the GLP-1s as well as the SGLT2 inhibitors, although there is limited data on people with both less than 30 for GFR and less than 30 for uACR, there is consistently available evidence of benefit on CKD progression across the board, and of course, some secondary analyses showing advantages with regard to cardiovascular outcome. Both therapies appear to offer consistency of cardio and kidney disease progression, regardless of estimated GFR and uACR, and I think that's the way we need to operate with our thinking right now until more conclusive data is available,” concluded Weir’s presentation.2

READ MORE: FDA Approves Vadadustat For Treatment of Anemia Due to CKD

For more on the 2024 Heart in Diabetes conference, check out our ongoing coverage.

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References
1. Estimated glomerular filtration rate (eGFR). National Kidney Foundation. Accessed June 10, 2024. https://www.kidney.org/atoz/content/gfr
2. Weir M. Outcome of advanced CKD without albuminuria; impact of SGLT2i & GLP-1ra. Presented at: 2024 Heart in Diabetes Conference; June 7-9; Philadelphia, PA.
3. Hickman RJ. What’s Important to Know About Microalbuminuria. Verywell Health. Published August 4, 2023. Accessed June 11, 2024. https://www.verywellhealth.com/microalbuminuria-overview-4684503
4. Kidney Failure Risk Factor: Urine Albumin-to-Creatinine Ration (UACR). National Kidney Foundation. Accessed June 11, 2024. https://www.kidney.org/content/kidney-failure-risk-factor-urine-albumin-to-creatinine-ration-uacr
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