Orlando, Fla. — Results from the EMPA-Kidney Trial of SGLT2 Inhibitors Empagliflozin people with chronic kidney disease With or without diabetes (CKD) more than added a second positive result from a large trial in this patient population.
EMPA-Kidney also tripled his overall research experience with the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of drugs. type 2 diabetes We have greatly expanded our knowledge of this class of patients across the spectrum of CKD severity and causes.
Main results EMPA-kidney It was publish online in the New England Journal of Medicine Announced on November 4th, here at Kidney Week 2022. previously reportedRegarding the trial’s primary efficacy outcome, treatment with empagliflozin (Jardiance) for a median of 2.0 years in patients with CKD compared the composite outcome of progression of CKD or death from cardiovascular causes to placebo. significantly reduced by 28%.
“Importantly, EMPA-Kidney expands the population at risk,” especially those with CKD without diabetes, proteinuriaand patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2Janani Langaswami, M.D., Ph.D., professor and nephrologist at The George Washington University School of Medicine and Health Sciences, Washington, DC. “This is a win for her stage 4 CKD patients,” she declared, reversing the “stage 4 nihilism” revealed by the low proportion of these patients in treatment trials in the past.
“EMPA-Kidney is a very welcome addition to the already strong evidence supporting SGLT2 inhibitor therapy for CKD patients,” she added.
The Oxford University-based research team that ran EMPA-Kidney quickly incorporated the results into a meta-analysis. This meta-analysis included 12 additional trials involving her SGLT2 inhibitors in more than 90,000 patients with all 13 trials involving tens of thousands of people with type 2 diabetes and high levels.risk of cardiovascular disease, or heart failure (reduced or maintained ejection fraction) or with CKD.
This new meta-analysis concluded that “SGLT-2 inhibitors safely reduce the risk of kidney disease progression and acute kidney injury [AKI] Regardless of your diabetes status,” said Dr. Natalie Staplin at Kidney Week 2022 hosted by the American Society of Nephrology.
Benefits of CKD regardless of diabetic status or type of CKD
The absolute benefits of SGLT2 inhibitor treatment in CKD patients outweigh the harms, and “the relative benefits do not appear to be altered by the first renal diagnosis that causes CKD,” says the Renal Research Group, University of Oxford, UK. said Staplin, a senior statistician at .
Two days after Staplin published its meta-analysis at Kidney Week 2022, the results Report publication of lancetshared with delegates at the American Heart Association (AHA) Science Session 2022 in Chicago.
“Before the EMPA-Kidney results, we knew that SGLT2 inhibitors were effective in patients with diabetes and CKD, but we found that CKD patients without diabetes, CKD subtypes, and minimal-to-normal It’s proteinuria,” commented Naveed Sattar, MBChB, PhD, Professor of Metabolic Medicine at the University of Glasgow, UK, who was nominated to discuss the report at the AHA conference.
fill the data gap
The EMPA-Kidney results filled many of these data gaps.The majority (54%) of his 6609 participants randomized had no history of diabetes, and the proportion of these patients in his SGLT2 study of patients with CKD was approximately 1400 in his previous CKD study. Since then he has more than tripled (mainly DAPA-CKD) to over 4900.
As far as etiology-based subgroups of CKD are concerned, EMPA-Kidney includes, in addition to patients with diabetic kidney disease, a significant number of patients with ischemic and hypertensive CKD, and patients with glomerular disease, including IgA nephropathy. was included, but polycystic kidney disease was an exclusion criterion, Satar noted.
Another important subgroup of CKD patients included in EMPA-Kidney was stage 4 CKD patients with eGFR between 20 and 29 mL/min/1.73m.2, accounting for 35% of the registrants. Also, patients with normal albuminuria levels with a urinary albumin-to-creatinine ratio (UACR) <30 mg/g accounted for 20% of the enrolled cohort, and a further 28% had a UACR between 30 and 300 mg/g. was.
By confirming the efficacy of SGLT2 inhibitors in this broadly representative sample of CKD patients, regardless of diabetic status, the EMPA-Kidney results suggest that SGLT2 inhibitors may serve as a ‘basic’ treatment for CKD patients. Sattar emphasized that this class, along with the results of established meta-analyses, is the cornerstone for treating virtually all patients with heart failure.
Expect guidelines to change
The results of the meta-analysis are “expected to change guidelines for chronic kidney disease,” write Sattar and co-author Patrick B. Mark, MBChB, PhD. Accompanying editorial.
They also suggest initiating treatment of CKD patients with SGLT2 inhibitors prior to or in parallel with renin-angiotensin system inhibitors. And they call on the nephrologist to “work with and empower primary care providers” to ensure early and widespread use of her SGLT2 inhibitors in CKD patients.
“The point of the meta-analysis is [for nephrologists] We need to work with primary care to introduce SGLT2 inhibitors and not hesitate when prescribing these agents,” Sattar said in an AHA talk.
Construction of DAPA-CKD to improve uptake of SGLT2 inhibitors in the US
Rangaswami, who was the second meta-analytical debater at the AHA conference, agreed.
“EMPA-Kidney will support DAPA-CKD and CREDENCE exam [the latter with canagliflozin]’ she emphasized.
“Hopefully, it builds on the signals from DAPA-CKD.” Additional data from EMPA-Kidney will facilitate US uptake of this class of therapy in patients with CKD. , this uptake was “unfortunately low,” she noted.
Evidence also suggests that empagliflozin and Dapagliflozin Rangaswami concluded that the SGLT2 inhibitors tested in DAPA-CKD (Farxiga) were similar in terms of benefit to CKD patients.
EMPA-Kidney was sponsored by Boehringer Ingelheim and Lilly, who co-market empagliflozin (Jardiance). Staplin reports receiving research funding from Boehringer Ingelheim, Lilly, and Novo Nordisk. Sattar reports being a consultant and speaker for Boehringer Ingelheim, Lilly and others. Rangaswamy has not reported any related financial relationships.
Kidney Week 2022. Summary of FR-OR69. Announced November 4, 2022.
Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @Mitchell Zoller