While choice of AHAs may be modified in patients with T2D and moderate or severe renal insufficiency, this is generally not the case in patients with mild renal insufficiency. Clinical trial data focused on this population, which represents ∼40% of patients with T2D, are lacking.

In a randomized, double-blind, active comparator-controlled clinical trial, the safety and efficacy of adding SITA (100 mg qd) or DAPA (10 mg qd) to treatment of patients with eGFR ≥60 and <90 mL/min/1.73 m2 and A1C ≥7.0% and ≤9.5% while on MET ± SU were assessed. The primary efficacy endpoint was change from baseline A1C at Week 24 (analyzed with a constrained longitudinal data analysis model), with a primary hypothesis of non-inferiority of SITA to DAPA based on the prespecified criterion of the upper bound of the between-treatment difference 95% CI (SITA minus DAPA) <0.3%; if the upper bound was <0.0%, SITA would be declared superior.

Treatment groups were well-balanced at baseline (n = 307 and 306, mean A1C [%] = 7.7 and 7.8, mean eGFR [mL/min/1.73 m2] = 79.4 and 76.9 for SITA and DAPA, respectively). At Week 24, LS mean changes from baseline A1C were -0.51% (SITA) and -0.36% (DAPA); between-group difference = -0.15%, 95% CI (-0.26, -0.04), p=0.006, confirming both non-inferiority and superiority of SITA vs. DAPA. The pre-specified analysis of 2 hour post-prandial glycemic excursion showed no significant difference between groups. The A1C goal of <7% was met by 43% (SITA) and 27% (DAPA) of patients. Treatments were well tolerated; there were significantly fewer patients with drug-related adverse events (AEs) with SITA than with DAPA, but summary AE profiles were otherwise similar.

In summary, SITA treatment over 24 weeks resulted in greater glycemic efficacy and greater % of patients at A1C goal than DAPA in patients with T2D and mild renal impairment who were inadequately controlled on MET ± SU.


R.S. Scott: None. J.D. Morgan: Employee; Self; Merck & Co., Inc. Z. Zimmer: Employee; Self; Merck & Co., Inc. R.L.H. Lam: Employee; Self; Merck & Co., Inc. E.A. O'Neill: Employee; Self; Merck & Co., Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. A. Raji: Employee; Self; Merck & Co., Inc..

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