Evaluation of Osmotic Diuresis and Volume Depletion Events in Patients with Type 2 Diabetes Mellitus (T2DM) Receiving Ertugliflozin

Abstract

Ertugliflozin (ERTU) is an SGLT2 inhibitor for the treatment of T2DM. Osmotic diuresis (OD), volume depletion (VD) and change in renal function were assessed in adults with T2DM. Pooled analyses were performed on data from 7 randomized, double blind, Phase 3 trials in patients receiving ERTU or non-ERTU (placebo [PBO] or active comparator) for at least 26 weeks, including a PBO pool (subset; n=1544) and a broad pool (all studies; N=4859; ERTU 5 mg: n=1716; ERTU 15 mg: n=1693; non-ERTU: n=1450). Mean age was 57.8 years, 25.8% were ≥65 years old, 51.8% were male and 27.7% were on diuretics. Mean eGFR was 85.3 mL/min/1.73 m2. Mean duration of T2DM was 7.9 years and mean baseline (BL) A1C was 8.2%. BL characteristics were similar in the PBO pool. In the broad pool, the incidence of OD events was 2.7%, 2.2%, and 1.4% with ERTU 5 mg, ERTU 15 mg, and non-ERTU, respectively; none were serious and ≤0.2% led to treatment discontinuation. The incidence of VD events was 1.9%, 1.4%, and 1.2% with ERTU 5 mg, ERTU 15 mg and non-ERTU, respectively; 0.2%, 0% and 0%, respectively, were serious and ≤0.1% led to treatment discontinuation. In patients with moderate renal impairment (RI; n=575, ∼12%), ≥65 years old, or on diuretics, ERTU led to a higher incidence of VD events than non-ERTU. In the PBO pool, the incidence of OD events was 2.9%, 2.4%, and 1.0% and the incidence of VD events was 0.8%, 1.0%, and 1.7% with ERTU 5 mg, ERTU 15 mg and PBO, respectively. There was no increase in the proportion of patients with orthostatic hypotension with ERTU treatment. ERTU was associated with small, early decreases in eGFR that returned to or towards BL during treatment. Mean decreases in eGFR were larger in patients with BL moderate RI and returned to BL after treatment discontinuation (recently published). ERTU is associated with OD, but does not generally lead to VD events or orthostatic hypotension. Consistent with this, observed decreases in eGFR were reversible during treatment or after discontinuation. Disclosure S.M. Patel: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; GlaxoSmithKline plc.. Stock/Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc. M.A. Hickman: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc. R. Frederich: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc., Bristol-Myers Squibb Company. B. Lauring: Employee; Self; Merck & Co., Inc. S. Terra: Employee; Self; Pfizer Inc. S.L. Johnson: Employee; Self; Pfizer Inc. S. Huyck: Employee; Self; Merck & Co., Inc. J.P. Mancuso: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc.. Employee; Spouse/Partner; Pfizer Inc.. Stock/Shareholder; Spouse/Partner; Pfizer Inc..