钠-葡萄糖共转运蛋白2抑制剂埃格列净研究进展
|
摘要
钠-葡萄糖共转运蛋白2抑制剂(Sodium glucose co-transporter-2 inhibitors,SGLT-2i)是近年来上市的用于治疗2型糖尿病(Type 2 diabetes,T2DM)的一类新药。埃格列净是第4个批准上市的用于治疗T2DM的SGLT-2i。本文对该药的降糖机制、药动学、临床试验、药品不良反应等进行综述。
Sodium glucose co-transporter-2 inhibitor( SGLT-2 i) is a newclass of drugs marketed in recent years for the treatment of type 2 diabetes. Ertugliflozin is the 4 th SGLT-2 i approved for the treatment of type 2 diabetes. This article reviews the hypoglycemic mechanism,pharmacokinetics,clinical trials,adverse drug reactions and other aspects of the drug.
Sodium glucose co-transporter-2 inhibitor( SGLT-2 i) is a newclass of drugs marketed in recent years for the treatment of type 2 diabetes. Ertugliflozin is the 4 th SGLT-2 i approved for the treatment of type 2 diabetes. This article reviews the hypoglycemic mechanism,pharmacokinetics,clinical trials,adverse drug reactions and other aspects of the drug.
引文
[1] International Diabetes Federation. Diabetes Atlas. Sixth Edition. 2014[EB/OL]. http://w w w. idf. org/diabetesatlas.[2015-6-1]
[2] Centers for Disease Control and Prevention. Diabetes Report Card,2012[EB/OL]. Atlanta,GA:Centers for Disease Control and Prevention,US Department of Health and Human Services; 2012. http://w w w. cdc. gov/diabetes/pubs/pdf/diabetesreportcard. pdf.[2015-6-1].
[3] Yang L,Shao J,Bian Y,et al. Prevalence of type 2 diabetes mellitus among inland residents in China(2000-2014):a meta-analysis[J]. J Diabetes Investig,2016,7(6):845-852.
[4] DeFronzo RA,Davidson JA,Del PS. The role of the kidneys in glucose homeostasis:a new path tow ards normalizing glycaemia[J]. Diabetes Obes M etab,2012,14(1):5-14.
[5] Thomas MC,Jandeleit-Dahm K,Bonnet F. Beyond glycosuria:exploring the intrarenal effects of SGLT-2 inhibition in diabetes[J]. Diabetes M etab,2014,40(6 Suppl 1):S17-S22.
[6] Sahasrabudhe V,Saur D,Matschke K,et al. A phase 1,randomized,placebo-and active-controlled crossover study to determine the effect of single-dose ertugliflozin on QTc interval in healthy volunteers[J]. Clin Pharmacol Drug Dev,2018,7(5):513-523.
[7] Miao Z,Nucci G,Amin N,et al. Pharmacokinetics,metabolism,and excretion of the antidiabetic agent ertugliflozin(PF-04971729)in healthy male subjects[J]. Drug M etab Dispos,2013,41(2):445-456.
[8] Kalgutkar AS,Tugnait M,Zhu T,et al. Preclinical species and human disposition of PF-04971729,a selective inhibitor of the sodium-dependent glucose cotransporter 2 and clinical candidate for the treatment of type 2 diabetes mellitus[J]. Drug M etab Dispos,2011,39(9):1609-1619.
[9] Sha S,Polidori D,Heise T,et al. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients w ith type 2 diabetes mellitus[J]. Diabetes Obes M etab,2014,16(11):1087-1095.
[10] Amin NB,Wang X,Jain SM,et al. Dose-ranging efficacy and safety study of ertugliflozin,a sodium-glucose co-transporter 2inhibitor,in patients w ith type 2 diabetes on a background of metformin[J]. Diabetes Obes M etab,2015,17(6):591-598.
[11] Terra SG,Focht K,Davies M,et al. Phase III,efficacy and safety study of ertugliflozin monotherapy in people w ith type 2diabetes mellitus inadequately controlled w ith diet and exercise alone[J]. Diabetes Obes M etab,2017,19(5):721-728.
[12] Rosenstock J,Frias J,Páll D,et al. Effect of ertugliflozin on glucose control,body w eight,blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy(VERTIS M ET)[J]. Diabetes Obes M etab,2018,20(3):520-529.
[13] Pratley RE,Eldor R,Raji A,et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 w eeks in patients w ith type 2 diabetes mellitus inadequately controlled w ith metformin:the VERTIS FACTORIAL randomized trial[J]. Diabetes Obes M etab,2018,20(5):1111-1120.
[14] Miller S,Krumins T,Zhou H,et al. Ertugliflozin and sitagliptin Co-initiation in patients with type 2 diabetes:the VERTIS SITA randomized study[J]. Diabetes Ther,2018,9(1):253-268.
[15] Dagogojack S,Liu J,Eldor R,et al. Efficacy and safety of the addition of ertugliflozin in patients w ith type 2 diabetes mellitus inadequately controlled w ith metformin and sitagliptin:the VERTIS SITA2 placebo-controlled randomized study[J]. Diabetes Obes M etab,2018,20(3):530-540.
[16] Hollander P,Liu J,Hill J,et al. Ertugliflozin compared with glimepiride in patients w ith type 2 diabetes mellitus inadequately controlled on metformin:the VERTIS SU randomized study[J]. Diabetes Ther,2018,9(1):193-207.
[17] Grunberger G,Camp S,Johnson J,et al. Ertugliflozin in patients w ith stage 3 chronic kidney disease and type 2 diabetes mellitus:the VERTIS RENAL randomized study[J]. Diabetes Ther,2018,9(1):49-66.
[18] Zinman B,Wanner C,Lachin JM,et al. Empagliflozin,cardiovascular outcomes,and mortality in type 2 diabetes[J]. N Engl J M ed,2015,373(22):2117-2128.
[19] Chao EC,Henry RR. SGLT2 inhibition--a novel strategy for diabetes treatment[J]. Nat Rev Drug Discov,2010,9(7):551-559.
[20] Cinti F,Moffa S,Impronta F,et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes:evidence to date[J]. Drug Des Devel Ther,2017,11:2905-2919.
[2] Centers for Disease Control and Prevention. Diabetes Report Card,2012[EB/OL]. Atlanta,GA:Centers for Disease Control and Prevention,US Department of Health and Human Services; 2012. http://w w w. cdc. gov/diabetes/pubs/pdf/diabetesreportcard. pdf.[2015-6-1].
[3] Yang L,Shao J,Bian Y,et al. Prevalence of type 2 diabetes mellitus among inland residents in China(2000-2014):a meta-analysis[J]. J Diabetes Investig,2016,7(6):845-852.
[4] DeFronzo RA,Davidson JA,Del PS. The role of the kidneys in glucose homeostasis:a new path tow ards normalizing glycaemia[J]. Diabetes Obes M etab,2012,14(1):5-14.
[5] Thomas MC,Jandeleit-Dahm K,Bonnet F. Beyond glycosuria:exploring the intrarenal effects of SGLT-2 inhibition in diabetes[J]. Diabetes M etab,2014,40(6 Suppl 1):S17-S22.
[6] Sahasrabudhe V,Saur D,Matschke K,et al. A phase 1,randomized,placebo-and active-controlled crossover study to determine the effect of single-dose ertugliflozin on QTc interval in healthy volunteers[J]. Clin Pharmacol Drug Dev,2018,7(5):513-523.
[7] Miao Z,Nucci G,Amin N,et al. Pharmacokinetics,metabolism,and excretion of the antidiabetic agent ertugliflozin(PF-04971729)in healthy male subjects[J]. Drug M etab Dispos,2013,41(2):445-456.
[8] Kalgutkar AS,Tugnait M,Zhu T,et al. Preclinical species and human disposition of PF-04971729,a selective inhibitor of the sodium-dependent glucose cotransporter 2 and clinical candidate for the treatment of type 2 diabetes mellitus[J]. Drug M etab Dispos,2011,39(9):1609-1619.
[9] Sha S,Polidori D,Heise T,et al. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients w ith type 2 diabetes mellitus[J]. Diabetes Obes M etab,2014,16(11):1087-1095.
[10] Amin NB,Wang X,Jain SM,et al. Dose-ranging efficacy and safety study of ertugliflozin,a sodium-glucose co-transporter 2inhibitor,in patients w ith type 2 diabetes on a background of metformin[J]. Diabetes Obes M etab,2015,17(6):591-598.
[11] Terra SG,Focht K,Davies M,et al. Phase III,efficacy and safety study of ertugliflozin monotherapy in people w ith type 2diabetes mellitus inadequately controlled w ith diet and exercise alone[J]. Diabetes Obes M etab,2017,19(5):721-728.
[12] Rosenstock J,Frias J,Páll D,et al. Effect of ertugliflozin on glucose control,body w eight,blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy(VERTIS M ET)[J]. Diabetes Obes M etab,2018,20(3):520-529.
[13] Pratley RE,Eldor R,Raji A,et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 w eeks in patients w ith type 2 diabetes mellitus inadequately controlled w ith metformin:the VERTIS FACTORIAL randomized trial[J]. Diabetes Obes M etab,2018,20(5):1111-1120.
[14] Miller S,Krumins T,Zhou H,et al. Ertugliflozin and sitagliptin Co-initiation in patients with type 2 diabetes:the VERTIS SITA randomized study[J]. Diabetes Ther,2018,9(1):253-268.
[15] Dagogojack S,Liu J,Eldor R,et al. Efficacy and safety of the addition of ertugliflozin in patients w ith type 2 diabetes mellitus inadequately controlled w ith metformin and sitagliptin:the VERTIS SITA2 placebo-controlled randomized study[J]. Diabetes Obes M etab,2018,20(3):530-540.
[16] Hollander P,Liu J,Hill J,et al. Ertugliflozin compared with glimepiride in patients w ith type 2 diabetes mellitus inadequately controlled on metformin:the VERTIS SU randomized study[J]. Diabetes Ther,2018,9(1):193-207.
[17] Grunberger G,Camp S,Johnson J,et al. Ertugliflozin in patients w ith stage 3 chronic kidney disease and type 2 diabetes mellitus:the VERTIS RENAL randomized study[J]. Diabetes Ther,2018,9(1):49-66.
[18] Zinman B,Wanner C,Lachin JM,et al. Empagliflozin,cardiovascular outcomes,and mortality in type 2 diabetes[J]. N Engl J M ed,2015,373(22):2117-2128.
[19] Chao EC,Henry RR. SGLT2 inhibition--a novel strategy for diabetes treatment[J]. Nat Rev Drug Discov,2010,9(7):551-559.
[20] Cinti F,Moffa S,Impronta F,et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes:evidence to date[J]. Drug Des Devel Ther,2017,11:2905-2919.