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Empagliflozin protects kidney function in Asian adults with type 2 diabetes

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January 10, 2019

The SGLT2 inhibitor empagliflozin can limit worsening nephropathy and slow the loss of kidney function in Asian adults with type 2 diabetes and cardiovascular disease, according to findings published in the Journal of Diabetes Investigation.

“Type 2 diabetes mellitus is frequently perceived as a disease of the Western world, and while it is widely known that the incidence of diabetes in Asian countries is predicted to increase over the coming years, it is less often recognized that the incidence is in fact already high throughout the Asian region,” Takashi Kadowaki, MD, PhD, professor and chairman of the department of diabetes and metabolic diseases in the graduate school of medicine at the University of Tokyo, and colleagues wrote. “An increasing body of evidence suggests that Asian individuals with type 2 diabetes mellitus are at greater risk of [diabetic kidney disease] than other racial groups. Unfortunately, options to prevent or treat [diabetic kidney disease] are limited. ... Given the pressing need for additional treatments, there has been extensive interest in possible kidney benefits of the type 2 diabetes mellitus drugs known as SGLT2 inhibitors.”

A subset of participants (n = 1,517; mean age, 61 years; 26.3%; mean HbA1c, 8.07%; mean estimated glomerular filtration rate, 73.9 mL/min/1.73 m2) who self-identified as of Asian ethnicity in the EMPA-REG OUTCOME study was used in the post hoc analysis conducted by Kadowaki and colleagues. All participants in the EMPA-REG OUTCOME study had type 2 diabetes, a BMI of 45 kg/m2 or less, some form of CVD and eGFR of 30 mL/min/1.73 m2 or more. The original study recruited participants from centers in Hong Kong, India, Indonesia, Japan, Korea, Malaysia, the Philippines, Singapore, Sri Lanka, Taiwan and Thailand, but any participant who self-reported Asian ethnicity was included as part of Kadowaki and colleagues’ analysis.

Participants were randomly assigned to empagliflozin (Jardiance, Boehringer Ingelheim) 10 mg, empagliflozin 25 mg or placebo daily. Serum creatinine and urine albumin to creatinine ratio were measured at the time of randomization and at 4, 12, 28 and 52 weeks, as well as every 14 weeks until the study’s conclusion and at a follow-up visit 30 days after the end of the study. Kadowaki and colleagues performed post hoc analysis of kidney outcomes in the subset of Asian participants, specifically focusing on incident or worsening nephropathy, progression to macroalbuminuria, composition doubling of serum creatinine and kidney function over time, which was measured by changes in eGFR. For participants with Asian ethnicity, the median observation time was 3.3 years.

Worsening nephropathy was reported in 15.5% of participants who were taking empagliflozin compared with 21.8% of participants in the placebo group (HR = 0.64; 95% CI, 0.49-0.83). The researchers also found that 13.7% of participants in the empagliflozin group progressed to macroalbuminuria compared with 19.3% of those taking placebo (HR = 0.64; 95% CI, 0.49-0.85). Additionally, the researchers said 1.8% of participants in the empagliflozin group had a doubling of serum creatinine accompanied by eGFR of 45 mL/min/1.73 m2 or less, initiation of renal-replacement therapy or death due to renal disease compared with 3.6% in the placebo group (HR = 0.48; 95% CI, 0.25-0.92).

In terms of kidney function during the 192 weeks of the study, the researchers reported that those in the empagliflozin group had a 5 mL/min/1.73 m2 increase in eGFR compared with the placebo group (95% CI, 3.7-6.3). Empagliflozin treatment also led to a reduction in urine albumin to creatinine ratio at week 12 and through week 164.

“These analyses of kidney outcomes in Asian patients from EMPA-REG OUTCOME showed improvements with empagliflozin across the various outcomes studied, with results consistent with those of the overall trial population,” the researchers wrote. “These results suggest the potential for empagliflozin to reduce the burden of early morbidity and mortality from [diabetic kidney disease] associated with Asian race in patients with type 2 diabetes mellitus.” – by Phil Neuffer

Disclosures: The EMPA-REG OUTCOME trial was funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Kadowaki reports that he has served as a consultant/speaker for Astellas, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Kowa, Kyowa Hakko Kirin, MSD, Novo Nordisk, Novartis, Ono, Sanofi, Sanwa, Sumitomo Dainippon Pharma, Taisho, Takeda and Tanabe-Mitsubishi, and has received research support from AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Kowa, MSD, Novo Nordisk, Ono, Sanofi, Takeda and Tanabe-Mitsubishi. Please see the study for all other authors’ relevant financial disclosures.