Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials

被引:28
作者
Tuttle, Katherine R. [1 ]
Levin, Adeera [2 ]
Nangaku, Masaomi [3 ]
Kadowaki, Takashi [3 ,4 ]
Agarwal, Rajiv [5 ]
Hauske, Sibylle J. [6 ,7 ]
Elsasser, Amelie [6 ]
Ritter, Ivana [6 ]
Steubl, Dominik [6 ,8 ]
Wanner, Christoph [9 ]
Wheeler, David C. [10 ]
机构
[1] Univ Washington, Providence Hlth Care, Spokane, WA 98195 USA
[2] Univ British Columbia, Vancouver, BC, Canada
[3] Univ Tokyo, Grad Sch Med, Tokyo, Japan
[4] Toranomon Gen Hosp, Tokyo, Japan
[5] Indiana Univ, Indianapolis, IN USA
[6] Boehringer Ingelheim Pharma GmbH Co KG, Ingelheim, Germany
[7] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med 5, Heidelberg, Germany
[8] Tech Univ Munich, Dept Nephrol, Fac Med, Munich, Germany
[9] Wurzburg Univ Clin, Wurzburg, Germany
[10] UCL, London, England
基金
美国国家卫生研究院;
关键词
GLOMERULAR-FILTRATION-RATE; SGLT2; INHIBITOR; OUTCOMES; CANAGLIFLOZIN; MORTALITY; MELLITUS;
D O I
10.2337/dc21-2034
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials. RESEARCH DESIGN AND METHODS This analysis pooled data from 19 randomized, placebo-controlled, phase 1-4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models. RESULTS Among a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37-0.96, P = 0.0323] and 0.48 [0.26-0.91, P = 0.0243], respectively) and edema (0.47 [0.33-0.68, P < 0.0001] and 0.44 [0.28-0.68, P = 0.0002], respectively). CONCLUSIONS Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.
引用
收藏
页码:1445 / 1452
页数:8
相关论文
共 33 条
  • [1] Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial
    Agarwal, Rajiv
    Joseph, Amer
    Anker, Stefan D.
    Filippatos, Gerasimos
    Rossing, Peter
    Ruilope, Luis M.
    Pitt, Bertram
    Kolkhof, Peter
    Scott, Charlie
    Lawatscheck, Robert
    Wilson, Daniel J.
    Bakris, George L.
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2022, 33 (01): : 225 - 237
  • [2] Diabetic Kidney Disease Challenges, Progress, and Possibilities
    Alicic, Radica Z.
    Rooney, Michele T.
    Tuttle, Katherine R.
    [J]. CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 12 (12): : 2032 - 2045
  • [4] [Anonymous], 2020, JARDIANCE PACK INS
  • [5] Chronic kidney disease in US adults with type 2 diabetes: An updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging
    Bailey R.A.
    Wang Y.
    Zhu V.
    Rupnow M.F.
    [J]. BMC Research Notes, 7 (1)
  • [6] Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes
    Bakris, George L.
    Agarwal, Rajiv
    Anker, Stefan D.
    Pitt, Bertram
    Ruilope, Luis M.
    Rossing, Peter
    Kolkhof, Peter
    Nowack, Christina
    Schloemer, Patrick
    Joseph, Amer
    Filippatos, Gerasimos
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (23) : 2219 - 2229
  • [7] Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial
    Barnett, Anthony H.
    Mithal, Ambrish
    Manassie, Jenny
    Jones, Russell
    Rattunde, Henning
    Woerle, Hans J.
    Broedl, Uli C.
    [J]. LANCET DIABETES & ENDOCRINOLOGY, 2014, 2 (05) : 369 - 384
  • [8] Predictors of chronic kidney disease in type 2 diabetes A longitudinal study from the AMD Annals initiative
    De Cosmo, Salvatore
    Viazzi, Francesca
    Pacilli, Antonio
    Giorda, Carlo
    Ceriello, Antonio
    Gentile, Sandro
    Russo, Giuseppina
    Rossi, Maria C.
    Nicolucci, Antonio
    Guide, Pietro
    Pontremoli, Roberto
    [J]. MEDICINE, 2016, 95 (27)
  • [9] Eknoyan G., 2013, Kidney Int Suppl, V3, P5
  • [10] Genital and urinary tract infections in diabetes: Impact of pharmacologically-induced glucosuria
    Geerlings, Suzanne
    Fonseca, Vivian
    Castro-Diaz, David
    List, James
    Parikh, Shamik
    [J]. DIABETES RESEARCH AND CLINICAL PRACTICE, 2014, 103 (03) : 373 - 381