SGLT2-INHIBITORS: A NOVEL CLASS FOR THE TREATMENT OF TYPE 2 DIABETES INTRODUCTION OF SGLT2-INHIBITORS IN CLINICAL PRACTICE

被引:31
作者
Cuypers, J. [1 ]
Mathieu, C. [2 ]
Benhalima, K. [2 ]
机构
[1] Katholieke Univ Leuven, UZ Gasthuisberg, Dept Internal Med, Louvain, Belgium
[2] Katholieke Univ Leuven, UZ Gasthuisberg, Dept Endocrinol, Louvain, Belgium
关键词
type; 2; diabetes; SGLT2-inhibitors; dapagliflozin; glycosuria; INADEQUATE GLYCEMIC CONTROL; SGLT2; INHIBITOR; DOUBLE-BLIND; DAPAGLIFLOZIN MONOTHERAPY; ADD-ON; INSULIN; MELLITUS; CANAGLIFLOZIN; HYPERGLYCEMIA; GLUCOSURIA;
D O I
10.2143/ACB.3349
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Treatment of type 2 diabetes (T2DM) continues to present challenges, with significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefit-risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiologicalconditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron, principally via the sodium-glucose cotransporter 2 (SGLT2). SGLT2- inhibitors are a new class of oral antidiabetics, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion, or action:Clinical results are promising with significant lowering of HbA1c without increased risk of hypoglycemia, reduction of body weight and reduction of systolic blood pressure. Dapagliflozin is the first highly selective SGLT2-inhibitor approved by the European Medecine Agency. Canagliflozin and empagliflozin are undergoing phase III trials. Actual safety issues are an increased risk for genital- and urinary tract infections and a possible increased risk for bladder and breast cancer. This led to refusal of dapagliflozin by the Food and Drug Administration (FDA). A large randomized control trial is therefore warranted by the FDA. This review, provides an overview of the Current evidence available so far on the therapeutic potential of the SGLT2-inhibitors for the treatment of T2DM.
引用
收藏
页码:287 / 293
页数:7
相关论文
共 37 条
[1]  
[Anonymous], 2011, ADV COMM M JUL 19
[2]   Dapagliflozin monotherapy in drug-naive patients with diabetes: a randomized-controlled trial of low-dose range [J].
Bailey, C. J. ;
Iqbal, N. ;
T'joen, C. ;
List, J. F. .
DIABETES OBESITY & METABOLISM, 2012, 14 (10) :951-959
[3]   Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial [J].
Bailey, Clifford J. ;
Gross, Jorge L. ;
Pieters, Anne ;
Bastien, Arnaud ;
List, James F. .
LANCET, 2010, 375 (9733) :2223-2233
[4]   Effects of Dapagliflozin on Body Weight, Total Fat Mass, and Regional Adipose Tissue Distribution in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin [J].
Bolinder, Jan ;
Ljunggren, Osten ;
Kullberg, Joel ;
Johansson, Lars ;
Wilding, John ;
Langkilde, Anna Maria ;
Sugg, Jennifer ;
Parikh, Shamik .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (03) :1020-1031
[5]   Sodium-dependent glucose transporter protein as a potential therapeutic target for improving glycemic control in diabetes [J].
Castaneda-Sceppa, Carmen ;
Castaneda, Francisco .
NUTRITION REVIEWS, 2011, 69 (12) :720-729
[6]   Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes [J].
Clar, Christine ;
Gill, James Alexander ;
Court, Rachel ;
Waugh, Norman .
BMJ OPEN, 2012, 2 (05)
[7]   The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia [J].
DeFronzo, R. A. ;
Davidson, J. A. ;
Del Prato, S. .
DIABETES OBESITY & METABOLISM, 2012, 14 (01) :5-14
[8]   Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies [J].
Del Prato, S. .
DIABETIC MEDICINE, 2009, 26 (12) :1185-1192
[9]   Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin [J].
Devineni, D. ;
Morrow, L. ;
Hompesch, M. ;
Skee, D. ;
Vandebosch, A. ;
Murphy, J. ;
Ways, K. ;
Schwartz, S. .
DIABETES OBESITY & METABOLISM, 2012, 14 (06) :539-545
[10]   MOLECULAR ADAPTATIONS OF GLUT1 AND GLUT2 IN RENAL PROXIMAL TUBULES OF DIABETIC RATS [J].
DOMINGUEZ, JH ;
CAMP, K ;
MAIANU, L ;
FEISTER, H ;
GARVEY, WT .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (02) :F283-F290