Renal physiology of glucose handling and therapeutic implications.

Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE

Publication: Oxford : Oxford University Press
Original Publication: [Berlin ; New York, NY] : Springer International, [c1986-

Diabetes Mellitus, Type 2/*drug therapy ; Glucose/*metabolism ; Hypoglycemic Agents/*pharmacology ; Kidney/*drug effects ; Renal Insufficiency, Chronic/*prevention & control ; Sodium-Glucose Transporter 2 Inhibitors/*pharmacology; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Glomerular Filtration Rate ; Humans ; Kidney/physiopathology ; Renal Insufficiency, Chronic/pathology

The rationale for using sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) has evolved over the last decade. Due to the effects on glucosuria and body weight loss, SGLT2 inhibitors were originally approved for glycemic control in T2D. Since glucosuria is attenuated in chronic kidney disease (CKD) Stages 3-5, initial regulatory approval for SGLT2 inhibitor use was limited to patients with T2D and preserved estimated glomerular filtration rate. Over time, however, it has become increasingly apparent that these therapies have a variety of important pharmacodynamic and clinical effects beyond glycemic lowering, including antihypertensive and antialbuminuric properties, and the ability to reduce glomerular hypertension. Importantly, these sodium-related effects are preserved across CKD stages, despite attenuated glycemic effects, which are lost at CKD Stage 4. With the completion of cardiovascular (CV) outcome safety trials-EMPA-REG OUTCOME, CANVAS Program and DECLARE TIMI-58-in addition to reductions in CV events, SGLT2 inhibition consistently reduces hard renal endpoints. Importantly, these CV and renal effects are independent of glycemic control. Subsequent data from the recent CREDENCE trial-the first dedicated renal protection trial with SGLT-2 inhibition-demonstrated renal and CV benefits in albuminuric T2D patients, pivotal results that have expanded the clinical importance of these therapies. Ongoing trials will ultimately determine whether SGLT2 inhibition will have a role in renal protection in other clinical settings, including nondiabetic CKD and type 1 diabetes.
(© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Curr Med Res Opin. 2014 Jul;30(7):1245-55. (PMID: 24708292)
Cardiovasc Diabetol. 2017 Mar 3;16(1):32. (PMID: 28253918)
Nat Rev Nephrol. 2017 Jan;13(1):11-26. (PMID: 27941935)
Lancet Diabetes Endocrinol. 2019 Jun;7(6):429-441. (PMID: 30992195)
J Am Heart Assoc. 2017 May 18;6(5):null. (PMID: 28522675)
Kidney Int. 2018 Jan;93(1):231-244. (PMID: 28860019)
Kidney Int. 2014 Nov;86(5):1057-8. (PMID: 25360497)
Diabetes Obes Metab. 2016 Jun;18(6):590-7. (PMID: 26936519)
N Engl J Med. 2011 Mar 3;364(9):818-28. (PMID: 21366473)
N Engl J Med. 2016 Mar 17;374(11):1094. (PMID: 26981940)
Diabetes Obes Metab. 2018 Aug;20(8):1988-1993. (PMID: 29573529)
J Hypertens. 2008 Aug;26(8):1619-28. (PMID: 18622241)
Diabetes Obes Metab. 2014 Nov;16(11):1087-95. (PMID: 24939043)
Diabetes Care. 2018 Sep;41(9):1938-1946. (PMID: 30026335)
Clin Sci (Lond). 2018 Jun 28;132(12):1329-1339. (PMID: 29954951)
Lancet Diabetes Endocrinol. 2014 May;2(5):369-84. (PMID: 24795251)
Diabetologia. 2014 Dec;57(12):2599-602. (PMID: 25280671)
Can J Diabetes. 2015 Jun;39(3):239-46. (PMID: 25600084)
Am J Physiol Renal Physiol. 2015 Jan 15;308(2):F77-83. (PMID: 25377916)
Diabetes Technol Ther. 2017 Sep;19(9):507-512. (PMID: 28749169)
Lancet Diabetes Endocrinol. 2016 Dec;4(12):1004-1016. (PMID: 27651331)
Adv Ther. 2017 Feb;34(2):436-451. (PMID: 27981497)
Diabetologia. 2019 Jul;62(7):1154-1166. (PMID: 31001673)
Obesity (Silver Spring). 2018 Jan;26(1):70-80. (PMID: 29165885)
Diabetologia. 2016 Sep;59(9):1860-70. (PMID: 27316632)
Diabetol Metab Syndr. 2017 Oct 4;9:78. (PMID: 29034006)
Kidney Int. 2018 Jul;94(1):26-39. (PMID: 29735306)
Diabetes. 2017 Jul;66(7):1939-1949. (PMID: 28408434)
Kidney Int. 2018 Sep;94(3):524-535. (PMID: 30045814)
N Engl J Med. 2016 Nov 10;375(19):1834-1844. (PMID: 27633186)
Cardiovasc Res. 2018 Feb 1;114(2):336-346. (PMID: 29016744)
Clin Ther. 2014 May;36(5):698-710. (PMID: 24726680)
Diabetes Obes Metab. 2013 May;15(5):463-73. (PMID: 23464594)
Intern Med. 2017 Oct 15;56(20):2739-2744. (PMID: 28924123)
Diabetes Care. 2014 May;37(5):1480-3. (PMID: 24595630)
Diabetes. 2018 Jun;67(6):1182-1189. (PMID: 29602791)
Lancet Diabetes Endocrinol. 2017 Aug;5(8):610-621. (PMID: 28666775)
Cardiovasc Diabetol. 2019 Apr 5;18(1):46. (PMID: 30953516)
Cardiovasc Diabetol. 2018 Jan 4;17(1):5. (PMID: 29301520)
Am J Physiol Renal Physiol. 2019 Mar 1;316(3):F449-F462. (PMID: 30539648)
N Engl J Med. 2015 Nov 26;373(22):2117-28. (PMID: 26378978)
Diabetes Care. 2009 Nov;32(11):2068-74. (PMID: 19651921)
J Am Coll Cardiol. 2019 Apr 23;73(15):1931-1944. (PMID: 30999996)
Am J Kidney Dis. 2019 Nov;74(5):713-715. (PMID: 31255334)
J Diabetes Complications. 1999 Jul-Aug;13(4):224-31. (PMID: 10616863)
Diabetes Care. 2018 Aug;41(8):e129-e130. (PMID: 29941496)
Circulation. 2016 Sep 6;134(10):752-72. (PMID: 27470878)
BMJ. 2011 Jul 26;343:d4169. (PMID: 21791495)
Int J Mol Sci. 2019 Feb 01;20(3):null. (PMID: 30717173)
Dig Dis Sci. 2020 Feb;65(2):623-631. (PMID: 30684076)
BMJ. 2019 Apr 9;365:l1328. (PMID: 30967375)
Diabetes Care. 2016 May;39(5):694-700. (PMID: 27006512)
Diabetes Care. 2018 Feb;41(2):356-363. (PMID: 29203583)
J Transl Med. 2019 Apr 16;17(1):127. (PMID: 30992077)
J Community Hosp Intern Med Perspect. 2018 Feb 06;8(1):21-22. (PMID: 29441161)
N Engl J Med. 2015 Jun 4;372(23):2197-206. (PMID: 26039600)
Diabetes Care. 1989 Nov-Dec;12(10):686-93. (PMID: 2612303)
Circulation. 2019 Jul 23;140(4):303-315. (PMID: 30773020)
Circulation. 2018 Nov 29;:null. (PMID: 30586745)
Cardiovasc Diabetol. 2014 Jan 29;13:28. (PMID: 24475922)
Lancet Diabetes Endocrinol. 2016 Dec;4(12):963-964. (PMID: 27651332)
Postgrad Med. 2016 May;128(4):371-80. (PMID: 27002421)
Kidney Int. 2014 Apr;85(4):962-71. (PMID: 24067431)
JACC Heart Fail. 2018 Aug;6(8):633-639. (PMID: 29525327)
Ann Intern Med. 2013 Aug 20;159(4):262-74. (PMID: 24026259)
Am J Physiol Regul Integr Comp Physiol. 2012 Jan 1;302(1):R75-83. (PMID: 21940401)
Cardiovasc Diabetol. 2019 Feb 7;18(1):16. (PMID: 30732594)
Am J Nephrol. 2019;49(4):331-342. (PMID: 30921791)
Diabetes Obes Metab. 2013 Sep;15(9):853-62. (PMID: 23668478)
J Clin Med. 2019 May 31;8(6):null. (PMID: 31159350)
Diabetes Care. 2019 Aug;42(8):1454-1463. (PMID: 31186299)
Can J Diabetes. 2018 Apr;42 Suppl 1:S201-S209. (PMID: 29650098)
Diabetologia. 2009 Nov;52(11):2288-98. (PMID: 19655124)
Diabetes Ther. 2017 Aug;8(4):851-861. (PMID: 28616806)
Cardiovasc Diabetol. 2017 Oct 23;16(1):138. (PMID: 29061124)
Obes Rev. 2018 Dec;19(12):1630-1641. (PMID: 30253050)
N Engl J Med. 2014 Oct 9;371(15):1392-406. (PMID: 25234206)
BMC Pharmacol Toxicol. 2017 Apr 10;18(1):23. (PMID: 28391776)
Circulation. 2014 Feb 4;129(5):587-97. (PMID: 24334175)
Diabetologia. 2019 Apr;62(4):621-632. (PMID: 30631892)
Cardiovasc Diabetol. 2019 Apr 1;18(1):45. (PMID: 30935417)
Eur Heart J. 2016 May 14;37(19):1526-34. (PMID: 26819227)
J Am Soc Nephrol. 2017 Apr;28(4):1023-1039. (PMID: 28143897)

Canada CIHR

Keywords: cardiovascular disease; diabetes; diabetic kidney disease; heart failure

0 (Hypoglycemic Agents)
0 (Sodium-Glucose Transporter 2 Inhibitors)
IY9XDZ35W2 (Glucose)

Date Created: 20200201 Date Completed: 20200904 Latest Revision: 20200904

20231215

PMC6993194

10.1093/ndt/gfz230

32003835