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Clinical Trial
. 2018 Nov;20(11):2532-2540.
doi: 10.1111/dom.13413. Epub 2018 Jul 10.

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

Paola Fioretto  1 , Stefano Del Prato  2 , John B Buse  3 , Ronald Goldenberg  4 , Francesco Giorgino  5 , Daniel Reyner  6 , Anna Maria Langkilde  7 , C David Sjöström  7 , Peter Sartipy  7   8 ; DERIVE Study Investigators
Affiliations
Clinical Trial

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

Paola Fioretto et al. Diabetes Obes Metab. 2018 Nov.

Erratum in

  • CORRIGENDUM.
    [No authors listed] [No authors listed] Diabetes Obes Metab. 2019 Jan;21(1):203. doi: 10.1111/dom.13563. Epub 2018 Nov 8. Diabetes Obes Metab. 2019. PMID: 30516008 Free PMC article. No abstract available.

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 m2 ; 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 m2 [-4.96, -0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post-treatment) (0.61 mL/min/1.73 m2 [-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.

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Conflict of interest statement

P. F. has served as an advisory board member and speaker for AstraZeneca, Eli Lilly and Boehringer Ingelheim. S. D. P. has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Intarcia, Janssen, Merck, Novartis, Novo Nordisk A/S, Laboratoires Servier, Sanofi and Takeda; has been a research investigator for Merck, Novartis and Takeda; and has been a speaker for Boehringer Ingelheim, Novartis and Takeda. J. B. B. has received contracted consulting fees, paid to his institution, and travel support from Adocia, AstraZeneca, Dexcom, Elcelyx Therapeutics, Eli Lilly, Intarcia Therapeutics, Lexicon, Metavention, NovaTarg, Novo Nordisk, Sanofi, and vTv Therapeutics; has received grant support from AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Lexicon, Novo Nordisk, Sanofi, Theracos and vTv Therapeutics; has served on the board of the AstraZeneca HealthCare Foundation; and holds stock options in Mellitus Health and PhaseBio. R. G. has served on advisory boards for Amgen, Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Takeda and Valeant; has served as a research investigator for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi and Takeda; and has been a speaker for Amgen, Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Mylan, Novo Nordisk, Sanofi, Laboratoires Servier and Valeant. F. G. has served as an advisory board member for AstraZeneca; has served as a research investigator for Eli Lilly; has served as a speaker for AstraZeneca and Eli Lilly; has received consulting fees from AstraZeneca, Sanofi, Abbott, Boehringer Ingelheim, Eli Lilly, MedImmune, Merck Sharp & Dohme and Roche Diabetes Care; and has received grants from Lifescan, Eli Lilly and Takeda. D. R. is an employee of AstraZeneca. A. M. L., C. D. S. and P. S. are employees of and shareholders in AstraZeneca.

Figures

Figure 1
Figure 1
Adjusted mean change from baseline (95% CI) in A, HbA1c; B, body weight; C, FPG; and D, Seated SBP, over 24 weeks (full analysis set). A, Mean baseline HbA1c (SD), 8.35% (1.06) with dapagliflozin and 8.03% (1.09) with placebo; adjusted mean change from baseline in HbA1c at Week 24 (95% CI), −0.37% (−0.56, −0.18) with dapagliflozin and −0.03% (−0.22, 0.16) with placebo. B, Mean baseline body weight (SD), 92.51 (16.73) kg with dapagliflozin and 88.30 (16.23) kg with placebo; adjusted mean change from baseline at Week 24 (95% CI), −3.17 kg (−3.76, −2.58) with dapagliflozin and −1.92 kg (−2.51, −1.34) with placebo. C, Mean baseline FPG (SD), 10.2 (3.7) mmol/L with dapagliflozin and 9.6 (3.0) mmol/L with placebo; adjusted mean change from baseline at Week 24 (95% CI), −1.2 mmol/L (−1.8, −0.6) and −0.3 mmol/L (−0.8, 0.3) with placebo. (D) Mean baseline seated SBP (SD), 135.7 (14.6) mm Hg with dapagliflozin and 135.0 (15.6) mm Hg with placebo; adjusted mean change from baseline at Week 24 (95% CI), −4.8 mm Hg (−7.7, −1.8) and −1.7 mm Hg (−4.6, 1.3) with placebo. CI, confidence interval; FPG, fasting plasma glucose; SBP, systolic blood pressure; SD, standard deviation
Figure 2
Figure 2
Adjusted mean change from baseline in eGFR (95% CI) during 24‐week treatment period and 3‐week follow‐up period (safety analysis set). †Data analysed with missing data assumptions specific to the repeated measures model, with missing data considered to be missing at random. ‡Data analysed separately using an extension of the analysis model to include Week 27, enabling the pattern in missing data to change with the inclusion of post‐treatment follow‐up. CI, confidence interval; eGFR, estimated glomerular filtration rate; SD, standard deviation
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References

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