SGLT2 inhibitors may lower risk for adverse renal outcomes vs. DPP-IV inhibitors
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The use of SGLT2 inhibitors with type 2 diabetes is associated with lower risks for end-stage renal disease and acute renal failure compared with DPP-IV inhibitor use, according to study findings from Hong Kong.
“DPP-IV inhibitors and SGLT2 inhibitors are commonly used second-line antidiabetic medications,” Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy in the Li Ka Shing Faculty of Medicine at the University of Hong Kong, told Healio. “Given that diabetes is associated with renal complications, our study suggests that using SGLT2 inhibitors could protect diabetic patients from adverse renal outcomes compared with using DPP-IV inhibitors.”
Cheung and colleagues conducted a retrospective cohort study of people with type 2 diabetes prescribed SGLT2 inhibitors or DPP-IV inhibitors between 2015 and 2018 in Hong Kong. Data were obtained from the Hospital Authority of Hong Kong’s Clinical Data Analysis and Reporting System. Participants using SGLT2 inhibitors were matched 1:4 with DPP-IV inhibitor users using propensity score matching based on the length of previous exposure to DPP-IV inhibitors. Incidences of ESRD, albuminuria and acute renal failure were collected through the end of the follow-up period on Dec. 31, 2020. The rate of change in estimated glomerular filtration rate was calculated using measurements taken every 3 months after the start of the follow-up period for up to 2 years.
The findings were published in The Journal of Clinical Endocrinology & Metabolism.
The study cohort included 6,333 people using SGLT2 inhibitors matched with 25,332 people using DPP-IV inhibitors. Of those taking SGLT2 inhibitors, 71.3% were using dapagliflozin (Farxiga, AstraZeneca) and 27.4% used empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly). The cohort was followed for a median of 3.8 years.
Participants using SGLT2 inhibitors had a lower risk for ESRD (HR = 0.51; 95% CI, 0.42-0.62; P < .001) and acute renal failure (HR = 0.59; 95% CI, 0.48-0.73; P < .001) compared with DPP-IV inhibitor users. There was no significant difference in albuminuria risk between the two groups in the main analysis. However, in sensitivity analysis accounting for potential bias due to drug discontinuation, SGLT2 inhibitor use was associated with a lower albuminuria risk compared with DPP-IV inhibitor use (HR = 0.5; 95% CI, 0.36-0.68; P < .001).
There were 617 propensity scoring-matched pairs included in the eGFR change analysis. Participants using SGLT2 inhibitors had a lower rate of eGFR change per year compared with DPP-IV inhibitor users (mean change, –0.06 mL/min/1.73 m2 vs. –0.625 mL/min/1.73 m2; P < .001).
In subgroup analysis, SGLT2 inhibitor use was associated with a lower risk for ESRD both for participants with a rapid eGFR decline of greater than 4% per year and those without a rapid eGFR decline (P for interaction = .008). In another subgroup analysis including only those with ongoing or previous DPP-IV use at the start of the study, use of SGLT2 inhibitors was significantly associated with a lower risk for ESRD (HR = 0.54; 95% CI, 0.43-0.69; P < .001) and acute renal failure (HR = 0.51; 95% CI, 0.39-0.69; P < .001) compared with continued DPP-IV inhibitor use.
“SGLT2 inhibitors are regarded not only as an antidiabetic agent but also as a cardiac- and renal-protective agent,” Cheung said. “Thus, the investigation of the pleiotropic effect of SGLT2 inhibitors is interesting and clinically significant. A recent meta-analysis of randomized clinical trials showed that SGLT2 inhibitors use might protect diabetic patients against pneumonia. A recently published real-world study, which was conducted by my PhD student, Philip Au, further supported this finding. Thus, further research of the pleiotropic effect of SGLT2 inhibitors using both clinical trials and real-world studies should be of clinical importance.”
For more information:
Ching-Lung Cheung, PhD, can be reached at lung1212@hku.hk.
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