The role of SGLT-2 inhibitors in managing type 2 diabetes

REFERENCES

1. ↵
   1. Neumiller JJ,
   2. White JR Jr.,
   3. Campbell RK

   . Sodium-glucose co-transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 2010; 70(4):377–385. doi:10.2165/11318680-000000000-00000

   OpenUrlCrossRefPubMed
2. ↵
   1. Bakris GL,
   2. Fonseca VA,
   3. Sharma K,
   4. Wright EM

   . Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int 2009; 75(12):1272–1277. doi:10.1038/ki.2009.87

   OpenUrlCrossRefPubMed
3. ↵
   1. Jabbour SA

   . SGLT2 inhibitors to control glycemia in type 2 diabetes mellitus: a new approach to an old problem. Postgrad Med 2014; 126(1):111–117. doi:10.3810/pgm.2014.01.2731

   OpenUrlCrossRefPubMed
4. ↵
   1. Nauck MA,
   2. Del Prato S,
   3. Meier JJ,
   4. et al

   . Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011; 34(9):2015–2022. doi:10.2337/dc11-0606

   OpenUrlAbstract/FREE Full Text
5. ↵
   1. Stenlöf K,
   2. Cefalu WT,
   3. Kim KA,
   4. et al

   . Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 2013; 15(4):372–382. doi:10.1111/dom.12054

   OpenUrlCrossRefPubMed
6. 1. Roden M,
   2. Weng J,
   3. Eilbracht J,
   4. et al

   . Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 2013; 1(3):208–219. doi:10.1016/S2213-8587(13)70084-6

   OpenUrlCrossRefPubMed
7. ↵
   1. Ferrannini E,
   2. Ramos SJ,
   3. Salsali A,
   4. Tang W,
   5. List JF

   . Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010; 33(10):2217–2224. doi:10.2337/dc10-0612

   OpenUrlAbstract/FREE Full Text
8. ↵
   1. Aronson R,
   2. Frias J,
   3. Goldman A,
   4. Darekar A,
   5. Lauring B,
   6. Terra SG

   . Long-term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study. Diabetes Obes Metab 2018; 20(6):1453–1460. doi:10.1111/dom.13251

   OpenUrlCrossRef
9. ↵
   1. Cefalu WT,
   2. Leiter LA,
   3. Yoon KH,
   4. et al

   . Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2013; 382(9896):941–950. doi:10.1016/S0140-6736(13)60683-2

   OpenUrlCrossRef
10. ↵
    1. Häring HU,
    2. Merker L,
    3. Seewaldt-Becker E,
    4. et al

    . Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 2014; 37(6):1650–1659. doi:10.2337/dc13-2105

    OpenUrlAbstract/FREE Full Text
11. ↵
    1. Rosenstock J,
    2. Frias J,
    3. Páll D,
    4. et al

    . Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET). Diabetes Obes Metab 2018; 20(3):520–529. doi:10.1111/dom.13103

    OpenUrlCrossRef
12. ↵
    1. Yale JF,
    2. Bakris G,
    3. Cariou B,
    4. et al

    . Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013; 15(5):463–473. doi:10.1111/dom.12090

    OpenUrlCrossRefPubMed
13. 1. Wilding JP,
    2. Woo V,
    3. Soler NG,
    4. et al

    . Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012; 156:(6)405–415. doi:10.7326/0003-4819-156-6-201203200-00003

    OpenUrlCrossRefPubMed
14. ↵
    1. Rosenstock J,
    2. Jelaska A,
    3. Frappin G,
    4. et al

    . Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care 2014; 37(7):1815–1823. doi:10.2337/dc13-3055

    OpenUrlAbstract/FREE Full Text
15. ↵
    1. Woo VC,
    2. Berard LD,
    3. Bajaj HS,
    4. Ekoé JM,
    5. Senior PA

    . Considerations for initiating a sodium-glucose co-transporter 2 inhibitor in adults with type 2 diabetes using insulin. Can J Diabetes 2018; 42(1):88–93. doi:10.1016/j.jcjd.2017.01.009

    OpenUrlCrossRef
16. ↵
    1. Einarson TR,
    2. Acs A,
    3. Ludwig C,
    4. Panton UH

    . Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol 2018; 17(1):83. doi:10.1186/s12933-018-0728-6

    OpenUrlCrossRefPubMed
17. ↵
    1. Kristensen SL,
    2. Preiss D,
    3. Jhund PS,
    4. et al

    . Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial. Circ Heart Fail 2016; 9(1):e002560. doi:10.1161/CIRCHEARTFAILURE.115.002560

    OpenUrlAbstract/FREE Full Text
18. ↵
    1. Kristensen SL,
    2. Mogensen UM,
    3. Jhund PS,
    4. et al

    . Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction). Circulation 2017; 135(8):724–735. doi:10.1161/CIRCULATIONAHA.116.024593

    OpenUrlAbstract/FREE Full Text
19. ↵
    1. Bertoni AG,
    2. Hundley WG,
    3. Massing MW,
    4. Bonds DE,
    5. Burke GL,
    6. Goff DC Jr.

    Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care 2004; 27(3):699–703. doi:10.2337/diacare.27.3.699

    OpenUrlAbstract/FREE Full Text
20. ↵
    1. Vaur L,
    2. Gueret P,
    3. Lievre M,
    4. Chabaud S,
    5. Passa P,
    6. DIABHYCAR Study Group (type 2 DIABetes, Hypertension, CARdiovascular Events and Ramipril) study

    . Development of congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria: observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study. Diabetes Care 2003; 26(3):855–860. doi:10.2337/diacare.26.3.855

    OpenUrlAbstract/FREE Full Text
21. ↵
    1. Zinman B,
    2. Wanner C,
    3. Lachin JM,
    4. et al

    . Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22):2117–2128. doi:10.1056/NEJMoa1504720

    OpenUrlCrossRefPubMed
22. ↵
    1. Neal B,
    2. Perkovic V,
    3. Mahaffey KW,
    4. et al

    . Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7):644–657. doi:10.1056/NEJMoa1611925

    OpenUrlCrossRefPubMed
23. ↵
    1. Wiviott SD,
    2. Raz I,
    3. Bonaca MP,
    4. et al

    . Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4):347–357. doi:10.1056/NEJMoa1812389

    OpenUrlCrossRefPubMed
24. ↵
    1. Cannon CP,
    2. Pratley R,
    3. Dagogo-Jack S,
    4. et al

    . Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med 2020; 383(15):1425–1435. doi:10.1056/NEJMoa2004967

    OpenUrlCrossRefPubMed
25. ↵
    1. Zelniker TA,
    2. Wiviott SD,
    3. Raz I,
    4. et al

    . SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393(10166):31–39. doi:10.1016/S0140-6736(18)32590-X

    OpenUrlCrossRefPubMed
26. ↵
    1. Kato ET,
    2. Silverman MG,
    3. Mosenzon O,
    4. et al

    . Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation 2019; 139(22):2528–2536. doi:10.1161/CIRCULATIONAHA.119.040130

    OpenUrlCrossRefPubMed
27. ↵
    1. Yancy CW,
    2. Jessup M,
    3. Bozkurt B,
    4. et al

    . 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128(16):1810–1852. doi:10.1161/CIR.0b013e31829e8807

    OpenUrlFREE Full Text
28. ↵
    1. McMurray JJV,
    2. Solomon SD,
    3. Inzucchi SE,
    4. et al

    . Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21):1995–2008. doi:10.1056/NEJMoa1911303

    OpenUrlCrossRefPubMed
29. ↵
    1. US Food and Drug Administration (FDA)

    . FDA approves new treatment for a type of heart failure. www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure. Accessed December 1, 2020.
30. ↵
    1. Packer M,
    2. Anker SD,
    3. Butler J,
    4. et al

    . Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383(15):1413–1424. doi:10.1056/NEJMoa2022190

    OpenUrlCrossRefPubMed
31. ↵
    1. Kosiborod M,
    2. Lam CSP,
    3. Kohsaka S,
    4. et al

    . Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol 2018; 71(23):2628–2639. doi:10.1016/j.jacc.2018.03.009

    OpenUrlFREE Full Text
32. ↵
    1. Baartscheer A,
    2. Schumacher CA,
    3. Wüst RC,
    4. et al

    . Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia 2017; 60(3):568–573. doi:10.1007/s00125-016-4134-x

    OpenUrlCrossRefPubMed
33. ↵
    1. Uthman L,
    2. Baartscheer A,
    3. Bleijlevens B,
    4. et al

    . Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia 2018; 61(3):722–726. doi:10.1007/s00125-017-4509-7

    OpenUrlCrossRef
34. ↵
    1. Baartscheer A,
    2. Hardziyenka M,
    3. Schumacher CA,
    4. et al

    . Chronic inhibition of the Na+/H+ - exchanger causes regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling. Br J Pharmacol 2008; 154(6):1266–1275. doi:10.1038/bjp.2008.189

    OpenUrlCrossRefPubMed
35. ↵
    1. Kang S,
    2. Verma S,
    3. Teng G,
    4. et al

    . Direct effects of empagliflozin on extracellular matrix remodeling in human cardiac fibroblasts: novel translational clues to EMPA-REG outcome. Can J Cardiol 2017; 33(10):S169. doi:10.1016/j.cjca.2017.07.330

    OpenUrlCrossRef
36. ↵
    1. USRDS

    . ESRD quarterly update. www.usrds.org/esrd-quarterly-update. Accessed December 2, 2020.
37. ↵
    1. Naylor KL,
    2. Kim SJ,
    3. McArthur E,
    4. Garg AX,
    5. McCallum MK,
    6. Knoll GA

    . Mortality in incident maintenance dialysis patients versus incident solid organ cancer patients: a population-based cohort. Am J Kidney Dis 2019; 73(6):765–776. doi:10.1053/j.ajkd.2018.12.011

    OpenUrlCrossRefPubMed
38. ↵
    1. Wen CP,
    2. Chang CH,
    3. Tsai MK,
    4. et al

    . Diabetes with early kidney involvement may shorten life expectancy by 16 years. Kidney Int 2017; 92(2):388–396. doi:10.1016/j.kint.2017.01.030

    OpenUrlCrossRefPubMed
39. ↵
    1. Perkovic V,
    2. Jardine MJ,
    3. Neal B,
    4. et al

    . Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380(24):2295–2306. doi:10.1056/NEJMoa1811744

    OpenUrlCrossRefPubMed
40. ↵
    1. Nespoux J,
    2. Vallon V

    . SGLT2 inhibition and kidney protection. Clin Sci (Lond) 2018; 132(12):1329–1339. doi:10.1042/CS20171298

    OpenUrlAbstract/FREE Full Text
41. ↵
    1. Wanner Ch,
    2. Inzucchi SE,
    3. Zinman B

    . Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(18):1801–1802. doi:10.1056/NEJMc1611290

    OpenUrlCrossRefPubMed
42. ↵
    1. Mosenzon O,
    2. Wiviott SD,
    3. Cahn A,
    4. et al

    . Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol 2019; 7(8):606–617. doi:10.1016/S2213-8587(19)30180-9

    OpenUrlCrossRefPubMed
43. ↵
    1. American Diabetes Association

    . 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care 2020; 43(suppl 1):S98–S110. doi:10.2337/dc20-S009

    OpenUrlAbstract/FREE Full Text
44. ↵
    1. Heerspink HJL,
    2. Karasik A,
    3. Thuresson M,
    4. et al

    . Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study. Lancet Diabetes Endocrinol 2020; 8(1):27–35. doi:10.1016/S2213-8587(19)30384-5

    OpenUrlCrossRef
45. ↵
    1. Ruggenenti P,
    2. Porrini EL,
    3. Gaspari F,
    4. et al

    . Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 2012; 35(10):2061–2068. doi:10.2337/dc11-2189

    OpenUrlAbstract/FREE Full Text
46. ↵
    1. Heerspink HJ,
    2. Perkins BA,
    3. Fitchett DH,
    4. Husain M,
    5. Cherney DZ

    . Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 2016; 134(10):752–772. doi:10.1161/CIRCULATIONAHA.116.021887

    OpenUrlAbstract/FREE Full Text
47. ↵
    1. Cherney DZI,
    2. Cooper ME,
    3. Tikkanen I,
    4. et al

    . Pooled analysis of phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int 2018; 93(1):231–244. doi:10.1016/j.kint.2017.06.017

    OpenUrlCrossRefPubMed
48. ↵
    1. Hollander P,
    2. Bays HE,
    3. Rosenstock J,
    4. et al

    . Coadministration of canagliflozin and phentermine for weight management in overweight and obese individuals without diabetes: a randomized clinical trial. Diabetes Care 2017; 40(5):632–639. doi:10.2337/dc16-2427

    OpenUrlAbstract/FREE Full Text
49. ↵
    1. Castellana M,
    2. Cignarelli A,
    3. Brescia F,
    4. et al

    . Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: a meta-analysis. Sci Rep 2019; 9(1):19351. doi:10.1038/s41598-019-55524-w

    OpenUrlCrossRef
50. ↵
    1. Ranjbar G,
    2. Mikhailidis DP,
    3. Sahebkar A

    . Effects of newer antidiabetic drugs on nonalcoholic fatty liver and steatohepatitis: think out of the box!. Metabolism 2019; 101:154001. doi:10.1016/j.metabol.2019.154001

    OpenUrlCrossRef
51. ↵
    1. Genc H,
    2. Dogru T,
    3. Kara M,
    4. et al

    . Association of plasma visfatin with hepatic and systemic inflammation in nonalcoholic fatty liver disease. Ann Hepatol 2013; 12(4):548–555. pmid:23813132

    OpenUrlPubMed
52. ↵
    1. Bolinder J,
    2. Ljunggren Ö,
    3. Kullberg J,
    4. et al

    . 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 Clin Endocrinol Metab 2012; 97(3):1020–1031. doi:10.1210/jc.2011-2260

    OpenUrlCrossRefPubMed
53. ↵
    1. Möller K,
    2. Ostermann AI,
    3. Rund K,
    4. et al

    . Influence of weight reduction on blood levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and oxylipins in obese subjects. Prostaglandins Leukot Essent Fatty Acids 2016; 106:39–49. doi:10.1016/j.plefa.2015.12.001

    OpenUrlCrossRef
54. ↵
    1. Kushiyama A,
    2. Tanaka K,
    3. Hara S,
    4. Kawazu S

    . Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5(6):787–795. doi:10.4239/wjd.v5.i6.787

    OpenUrlCrossRefPubMed
55. ↵
    1. Fralick M,
    2. Chen SK,
    3. Patorno E,
    4. Kim SC

    . Assessing the risk for gout with sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: a population-based cohort study. Ann Intern Med 2020; 172(3):186–194. doi:10.7326/M19-2610

    OpenUrlCrossRefPubMed
56. ↵
    1. US Food and Drug Administration (FDA)

    . FDA removes boxed warning about risk of leg and foot amputations for the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin. Accessed December 2, 2020.
57. ↵
    1. Bersoff-Matcha SJ,
    2. Chamberlain C,
    3. Cao C,
    4. Kortepeter C,
    5. Chong WH

    . Fournier gangrene associated with sodium-glucose cotransporter-2 inhibitors: a review of spontaneous postmarketing cases. Ann Intern Med 2019; 170(11):764–769. doi:10.7326/M19-0085

    OpenUrlCrossRefPubMed
58. ↵
    1. Handelsman Y,
    2. Henry RR,
    3. Bloomgarden ZT,
    4. et al

    . American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the association of SGLT-2 INHIBITORS and diabetic ketoacidosis. Endocr Pract 2016; 22(6):753–762. doi:10.4158/EP161292.PS

    OpenUrlCrossRefPubMed
59. ↵
    1. Ogawa W,
    2. Sakaguchi K

    . Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig 2016; 7(2):135–138. doi:10.1111/jdi.12401

    OpenUrlCrossRefPubMed
60. ↵
    1. Kibbey RG

    . SGLT-2 inhibition and glucagon: Cause for alarm? Trends Endocrinol Metab 2015; 26(7):337–338. doi:10.1016/j.tem.2015.05.011

    OpenUrlCrossRefPubMed
61. ↵
    1. Thiruvenkatarajan V,
    2. Meyer EJ,
    3. Nanjappa N,
    4. Van Wijk RM,
    5. Jesudason D

    . Perioperative diabetic ketoacidosis associated with sodium-glucose co-transporter-2 inhibitors: a systematic review. Br J Anaesth 2019; 123(1):27–36. doi:10.1016/j.bja.2019.03.028

    OpenUrlCrossRef
62. ↵
    Drug Topics. FDA approves label changes to SGLT2 inhibitors. https://www.drugtopics.com/view/fda-approves-safety-labeling-changes-sglt2-inhibitors. Accessed November 2, 2020.
63. ↵
    1. Garber AJ,
    2. Handelsman Y,
    3. Grunberger G,
    4. et al

    . Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2020 Executive Summary. Endocr Pract 2020; 26(1):107–139. doi:10.4158/CS-2019-0472

    OpenUrlCrossRef
64. ↵
    1. Dandona P,
    2. Mathieu C,
    3. Phillip M,
    4. et al

    . Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study. Diabetes Care 2018; 41(12):2552–2559. doi:10.2337/dc18-1087

    OpenUrlAbstract/FREE Full Text
65. ↵
    1. Rosenstock J,
    2. Marquard J,
    3. Laffel LM,
    4. et al

    . Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE Trials. Diabetes Care 2018; 41(12):2560–2569. doi:10.2337/dc18-1749

    OpenUrlAbstract/FREE Full Text
66. ↵
    1. Henry RR,
    2. Thakkar P,
    3. Tong C,
    4. Polidori D,
    5. Alba M

    . Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type 1 diabetes. Diabetes Care 2015; 38(12):2258–2265. doi:10.2337/dc15-1730

    OpenUrlAbstract/FREE Full Text
67. ↵
    1. Garg SK,
    2. Henry RR,
    3. Banks P,
    4. et al

    . Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med 2017; 377(24):2337–2348. doi:10.1056/NEJMoa1708337

    OpenUrlCrossRefPubMed