Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study

<jats:sec><jats:title>Aims</jats:title><jats:p>Dapagliflozin is a selective inhibitor of sodium glucose co‐transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45–59 mL/min/1.73 m<jats:sup>2</jats:sup>; chronic kidney disease [CKD] stage 3A).</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>In this double‐blind, parallel group, Phase 3 study (NCT02413398, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</jats:ext-link>) patients with inadequately controlled T2D (HbA1c 7.0%‐11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N = 160) or matching placebo (N = 161) for 24 weeks. Randomization was stratified by pre‐enrolment glucose‐lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], −0.34% [−0.53, −0.15]; <jats:italic>P</jats:italic> < 0.001), body weight (difference [95% CI], −1.25 kg [−1.90, −0.59]; <jats:italic>P</jats:italic> < 0.001), fasting plasma glucose (difference [95% CI], −0.9 mmol/L [−1.5, −0.4]; <jats:italic>P</jats:italic> = 0.001) and systolic blood pressure (difference [95% CI], −3.1 mm Hg [−6.3, 0.0]; <jats:italic>P</jats:italic> < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (−2.49 mL/min/1.73 m<jats:sup>2</jats:sup> [−4.96, −0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post‐treatment) (0.61 mL/min/1.73 m<jats:sup>2</jats:sup> [−1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The findings of this study (NCT02413398, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</jats:ext-link>) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.</jats:p></jats:sec>