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

Abstract

Aims

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 ²; chronic kidney disease [CKD] stage 3A).

Materials and methods

In this double‐blind, parallel group, Phase 3 study (NCT02413398, http://clinicaltrials.gov) 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.

Results

At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], −0.34% [−0.53, −0.15]; P < 0.001), body weight (difference [95% CI], −1.25 kg [−1.90, −0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], −0.9 mmol/L [−1.5, −0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], −3.1 mm Hg [−6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (−2.49 mL/min/1.73 m ² [−4.96, −0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post‐treatment) (0.61 mL/min/1.73 m ² [−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.

Conclusions

The findings of this study (NCT02413398, http://clinicaltrials.gov) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.