Assessment of Adverse Renal Effects in Patients with Type 2 Diabetes Mellitus (T2DM) Receiving Ertugliflozin

Ertugliflozin (ERTU) is a SGLT2 inhibitor for the treatment of T2DM. Adverse renal effects were assessed in adults with T2DM receiving ERTU relative to placebo (PBO) or active comparators in pooled analyses of 7 randomized, double-blind, Phase 3 trials. Patients (N=4859) received ERTU 5 mg (n=1716), ERTU 15 mg (n=1693), or non-ERTU (PBO, glimepiride or sitagliptin; n=1450) for up to 2 years. Mean age was 57.8 years, 25.8% were ≥65 years old and 51.8% were males. Mean eGFR was 85.3 mL/min/1.73 m² and ∼12% had moderate renal impairment (RI; eGFR <60 mL/min/1.73 m²). The mean duration of T2DM was 7.9 years and mean baseline A1C was 8.2%.

The incidence of renal-related AEs was low across the groups (ERTU 5 mg, 0.6%; ERTU 15 mg, 0.8%; non-ERTU, 0.4%); few were serious (0.1% in all groups) or led to treatment discontinuation (0.1%, 0.2% and 0.1%, respectively). Subgroup analyses demonstrated that in patients with moderate RI, renal-related AEs were more frequent in the ERTU groups relative to the non-ERTU group (ERTU 5 mg, 3.6%; ERTU 15 mg, 2.1%; non-ERTU, 1.1%). Incidence of renal-related AEs was similar across groups for patients ≥65 years old (excluding those with moderate RI at baseline) (ERTU 5 mg, 0.3%; ERTU 15 mg, 1.0%; non-ERTU, 0.8%) or those using diuretics (ERTU 5 mg, 1.2%; ERTU 15 mg, 0.8%; non-ERTU, 0.8%) or ACE/ARB (ERTU 5 mg, 0.9%; ERTU 15 mg, 0.9%; non-ERTU, 0.5%).

Independent blinded adjudication for causality was performed for pre-specified renal-related AEs and renal laboratory changes from baseline. Four patients had renal events that were adjudicated as causally related to study medication (“possible” or “very likely”; 1 in the ERTU 5 mg group, 2 in the ERTU 15 mg group and 1 in the non-ERTU group).

In conclusion, there was no increased risk of adverse renal effects in patients with T2DM receiving ERTU relative to PBO or active comparators, except in those with baseline moderate RI.