Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study. Issue 11 (10th July 2018)

• Record Type: Journal Article
• Authors: Fioretto, Paola; Del Prato, Stefano; Buse, John B.; Goldenberg, Ronald; Giorgino, Francesco; Reyner, Daniel; Langkilde, Anna Maria; Sjöström, C. David; Sartipy, Peter
• Is Part Of: Diabetes, obesity & metabolism. Volume 20:Issue 11(2018)
• Page Start: 2532
• Page End: 2540
• Publication Date: 2018-07-10
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13413
• Languages: English
• ISSNs: 1462-8902

Abstract

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, 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, clinicaltrials.gov ) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.