OPTIMISE-CKD: Dapagliflozin is Effective for Patients with CKD, Low Albuminuria

Navdeep Tangri, MD, PhD

Credit: University of Manitoba

Dapagliflozin 10 mg may be an effective treatment option for patients with chronic kidney disease (CKD) and urinary albumin-to-creatinine ratio (UACR) < 200 mg/g, a patient population in which its use had not been extensively studied despite the treatment’s broad indication.¹

Results from OPTIMISE-CKD, billed as the first study to assess the real-world effectiveness of dapagliflozin 10 mg in patients with CKD and UACR < 200 mg/g, showed dapagliflozin initiation was associated with a clinically meaningful attenuation of estimated glomerular filtration rate (eGFR) slope, a finding further replicated in a subgroup of patients without type 2 diabetes.¹

According to the US Centers for Disease Control and Prevention, an estimated 37 million adults in the US have CKD, most of whom are undiagnosed. CKD can progress to kidney failure, early cardiovascular disease, and even death, underscoring the importance of prevention and management efforts. In 2021, dapagliflozin became the first sodium-glucose cotransporter 2 inhibitor to be approved by any regulatory agency for patients with CKD irrespective of diabetes status, but its use in certain patient populations remains underexplored.^2,3

“Despite its broad indication, use of dapagliflozin 10 mg for CKD among patients with urinary albumin-to-creatinine ratio < 200 mg/g may be hindered by the limited number of studies performed in this group of patients, particularly among those without type 2 diabetes,” wrote Navdeep Tangri, MD, PhD, associate professor in the division of nephrology at the University of Manitoba, and colleagues.¹

Seeking to gain a better understanding of the real-world utilization of dapagliflozin 10 mg following its approval for CKD in the US and Japan, investigators examined de-identified data from Optum’s Clinformatics® Data Mart database, Medical Data Vision Co. Ltd database, and Real World Data Co. Ltd databases.¹

Additionally, investigators assessed the effect of initiating versus not initiating dapagliflozin 10 mg on kidney function decline in patients with UACR < 200 mg/g by matching dapagliflozin initiators in a 1:1 ratio to a potential comparator who had not initiated treatment on the same date and had the closest matching propensity score. Up to 5 potential comparators were randomly sampled for each dapagliflozin initiator in chronological order of their index dates and matched based on age, sex, heart failure diagnosis, type 2 diabetes diagnosis, and RASi prescription.¹

Patients were followed from index date until they were lost to follow-up, died, or the study period ended, whichever came first. The primary outcome was eGFR slope between index and the end of follow-up.¹

In total, 20,407 dapagliflozin initiators were included in the analysis, with a median age of 73 (US), 77 (Japan, Real World Data database) and 71 years (Japan, Medical Data Vision database). Investigators noted dapagliflozin 10 mg was initiated in patients across all CKD stages, but mostly in those with stage 3–4 CKD (69–81% across databases).¹

In general, the most commonly recorded comorbidities were type 2 diabetes, hypertension, heart failure, and other cardiovascular diseases. At baseline, a RASi was prescribed in 53–81% of patients.¹

Eligible but untreated patients were older and had a higher eGFR and lower comorbidity burden than initiators. Fewer patients in this group had a RASi prescription.¹

After propensity score matching 2972 dapagliflozin 10 mg initiators at a 1:1 ratio with a comparator, baseline characteristics were well balanced between the groups. Following dapagliflozin initiation, the difference in median eGFR slope between initiators and matched non-initiators was 1.07 mL/min/1.73 m2/year (95% confidence interval [CI], 0.40 to 1.74) in all patients with UACR < 200 mg/g. Of note, the benefit of dapagliflozin 10 mg initiation was observed across the entire eGFR slope distribution among patients with UACR < 200 mg/g.¹

A subgroup analysis was performed among patients who did not have a recorded diagnosis of type 2 diabetes, diabetic kidney disease, or a prescription for glucose-lowering drugs in their history. In total, 275 dapagliflozin initiators were matched in a 1:1 ratio using propensity scores. Upon analysis, the difference was 1.28 mL/min/1.73 m2/year (95% CI, −1.56 to 4.12) in favor of dapagliflozin 10 mg initiation.¹

Despite the significance of these findings, investigators pointed out several limitations that may have impacted the study’s results. These included, but were not limited to, heterogeneity between the US and Japanese populations included in the analysis, missing variables due to database design, potential differences in follow-up practices between initiators and comparators, the short observation window, and lack of safety data for review.¹

“In a real-world cohort of patients with CKD and UACR < 200 mg/g, initiating dapagliflozin 10 mg was associated with a clinically meaningful attenuation of eGFR slope, supplementing available clinical efficacy evidence and suggesting that dapagliflozin effectiveness may extend to patients with lower levels of albuminuria," investigators concluded.¹

References:

1. Tangri N, Rastogi A, Nekeman-Nan C, et al. Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan. Adv Ther (2024). https://doi.org/10.1007/s12325-023-02773-x
2. US Centers for Disease Control and Prevention. Chronic Kidney Disease Basics. Chronic Kidney Disease Initiative. February 28, 2022. Accessed January 26, 2024. https://www.cdc.gov/kidneydisease/basics.html
3. US Food and Drug Administration. FDA Approves Treatment for Chronic Kidney Disease. Press Announcements. April 30, 2021. Accessed January 26, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease