Physicians' Academy for Cardiovascular Education
Acute reversible decline in eGFR seen with SGTL2 inhibitor in T2DM patients with or without HF

Acute reversible decline in eGFR seen with SGTL2 inhibitor in T2DM patients with or without HF

Apr. 30, 2017 - news

Paris, France | Empagliflozin decreases risk of kidney function decline in type 2 diabetes: slope analyses in patients with and without heart failure at baseline from the EMPA-REG OUTCOME trial

Presented at ESC Heart Failure 2017 by Alfred CHUENG (Salt Lake City, UT, USA)

Background

The EMPA-REG OUTCOME trial evaluated the effect of the SGLT2 inhibitor empagliflozin (10 mg qd or 25 mgqd), in comparison to placebo, in 7020 patients with type 2 diabetes (T2DM) and established CV disease, for a median follow-up of 3.1 years. According to inclusion criteria, patients had eGFR (MDRD) ≥30 mL/min/1.73m2. Baseline characteristics overall were quite similar in placebo- or empagliflozin-treated patients, including the percentage of persons with eGFR <60 mL/ min/1.73m2, namely 26% in both groups.

The major results of the EMPA-REG OUTCOME trial included that compared to placebo, empagliflozin decreased the primary composite outcome of CV death, nonfatal MI or nonfatal stroke (HR: 0.86, 95%CI: 0.74-0.99, P=0.04) and the composite outcome of CV death or adjudicated heart failure (HF) hospitalisation (HR: 0.66, 95%CI: 0.55-0.79, P<0.0001).

The current study focusses on the observation that empagliflozin caused an acute, apparently reversible decline in eGFR, followed by long-term renoprotection. This study aims to assess effects of empagliflozin on the rate of change in eGFR over time in patients with (n=654) or without (n=6013) HF at baseline in the EMPA-REG OUTCOME trial. To this end, eGFR slopes were calculated using random-intercept and time-coefficient models, accounting for multiple baseline factors. eGFR slopes were calculated for three pre-specified time periods: acute phase (baseline to week 4 of treatment), chronic phase (week 4 to end of treatment) and post-treatment (to 1 month after the end of treatment).

Main results

Conclusion

These analyses show that eGFR slope analyses represent a useful method to investigate the effect of SGLT2 inhibitors on kidney function. Furthermore, it showed that the SGLT2 inhibitor empagliflozin caused an acute decline in eGFR (on a high background of ACEi/ARB use), which is apparently reversible upon stopping treatment. Empagliflozin appeared to prevent a decline in eGFR seen in patients receiving placebo. This pattern of eGFR changes was similar in patients with and without pre-existing HF.

Ongoing trials are further investigating the effects of empagliflozin on kidney function in patients (with or without diabetes) with HFrEF (EMPEROR-reduced) and with HFpEF (EMPEROR-preserved).

During the discussion, dr. Giuseppe M C ROSANO (London, GB) postulated that maybe an initial diuretic effect may explain the observations, as also an initial reduction of body weight was seen. Thus, the effect on eGFR may represent a diuretic effect rather than an effect of the drug itself. Also, he noted that while one would like to keep renal function in good shape, the drug lowers mortality and morbidity, which is outweighs the effects on renal function.

Disclosures

Our coverage of ESC HF 2017 is based on the information provided during the congress.