Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

被引:0
|
作者
André J. Scheen
机构
[1] University of Liège,Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM)
[2] CHU Liège,Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine
来源
Clinical Pharmacokinetics | 2015年 / 54卷
关键词
Chronic Kidney Disease; Glycaemic Control; Normal Renal Function; SGLT2 Inhibitor; Canagliflozin;
D O I
暂无
中图分类号
学科分类号
摘要
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin). These SGLT2 inhibitors share similar pharmacokinetic characteristics with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug. Pharmacokinetic parameters are slightly altered in the case of chronic kidney disease (CKD). While no dose adjustment is required in the case of mild CKD, SGLT2 inhibitors may not be used or only at a lower daily dose in patients with moderate CKD. Furthermore, the pharmacodynamic response to SGLT2 inhibitors as assessed by urinary glucose excretion declines with increasing severity of renal impairment as assessed by a reduction in the estimated glomerular filtration rate. Nevertheless, the glucose-lowering efficacy and safety of SGLT2 inhibitors are almost comparable in patients with mild CKD as in patients with normal kidney function. In patients with moderate CKD, the efficacy tends to be dampened and safety concerns may occur. In patients with severe CKD, the use of SGLT2 inhibitors is contraindicated. Thus, prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor. The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention because of preliminary favourable results in animal models.
引用
收藏
页码:691 / 708
页数:17
相关论文
共 50 条
  • [21] Clinical and Economic Rationale for the Early use of SGLT2 Inhibitors in Patients with Type 2 Diabetes
    Mannucci, Edoardo
    Mangia, Pier Paolo
    Pradelli, Lorenzo
    FARMECONOMIA-HEALTH ECONOMICS AND THERAPEUTIC PATHWAYS, 2020, 21 : 3 - 20
  • [22] RISK OF KIDNEY DISEASE PROGRESSION AND EFFICACY OF SGLT2 INHIBITION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
    Moura, Filipe
    Berg, David
    Bellavia, Andrea
    Mosenzon, Ofri
    Dwyer, Jamie
    Scirica, Benjamin M.
    Wiviott, Stephen
    Bhatt, Deepak L.
    Raz, Itamar
    Feinberg, Mark William
    Morrow, David A.
    Sabatine, Marc Steven
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2023, 81 (08) : 1808 - 1808
  • [23] SGLT2 inhibitors for treatment of chronic kidney disease
    Davis, S.
    SA PHARMACEUTICAL JOURNAL, 2024, 91 (02) : 26 - 28
  • [24] Effects of SGLT2 inhibitors on weight loss in patients with type 2 diabetes mellitus
    Ribola, F. A.
    Cancado, F. B.
    Schoueri, J. H. M.
    De Toni, V. F.
    Medeiros, V. H. R.
    Feder, D.
    EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2017, 21 (01) : 199 - 211
  • [25] The effect of SGLT2 inhibitors on drugnaive obese type 2 diabetes mellitus patients
    Chikazawa, Shinji
    Matsuhashi, Yuki
    Tando, Yusuke
    Daimon, Makoto
    DIABETES RESEARCH AND CLINICAL PRACTICE, 2016, 120 : S103 - S103
  • [27] Role of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus
    Anna Solini
    Acta Diabetologica, 2016, 53 : 863 - 870
  • [28] PRIMARY CARE USE OF SGLT2 INHIBITORS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CARDIOVASCULAR DISEASE - ARE WE MISSING A TRICK?
    Higson, David
    Turley, Andrew
    HEART, 2021, 107 : A153 - A154
  • [29] SGLT2 inhibitors: the future for treatment of type 2 diabetes mellitus and other chronic diseases
    Christoph Wanner
    Nikolaus Marx
    Diabetologia, 2018, 61 : 2134 - 2139
  • [30] Clinical implication of SGLT2 inhibitors in type 2 diabetes
    Go Woon Kim
    Sung Hyun Chung
    Archives of Pharmacal Research, 2014, 37 : 957 - 966