SGLT2 inhibitors in the management of type 2 diabetes

Endocrine

Volumn 53, Issue 2, 2016, Pages 364-372

  Monica Reddy, R P ^a   Inzucchi, Silvio E ^b  

^a GRIFFIN HOSPITAL   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Antihyperglycemic therapy; SGLT2 inhibitors; Type 2 diabetes mellitus

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; HEMOGLOBIN A1C; PLACEBO; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; ANTIDIABETIC AGENT; GLYCOSYLATED HEMOGLOBIN; METFORMIN; SODIUM GLUCOSE COTRANSPORTER 2;

ADVERSE OUTCOME; DEHYDRATION; DIABETIC KETOACIDOSIS; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG TOLERABILITY; GENITAL TRACT INFECTION; GLOMERULUS FILTRATION RATE; HEMODYNAMICS; HUMAN; HYPOGLYCEMIA; HYPOVOLEMIA; MYCOSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; RISK FACTOR; URINARY TRACT INFECTION; ANTAGONISTS AND INHIBITORS; BLOOD; COMBINATION DRUG THERAPY; DIABETES MELLITUS, TYPE 2; TREATMENT OUTCOME;

DIABETES MELLITUS, TYPE 2; DRUG THERAPY, COMBINATION; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; SODIUM-GLUCOSE TRANSPORTER 2; TREATMENT OUTCOME;

EID: 84976259091     PISSN: 1355008X     EISSN: 15590100     Source Type: Journal    
DOI: 10.1007/s12020-016-0943-4     Document Type: Review

References (51)

1. J.R. Ehrenkranz, N.G. Lewis, C.R. Kahn, J. Roth, Phlorizin: a review. Diabetes Metab. Res. Rev. 21(1), 31–38 (2005). doi:10.1002/dmrr.532
2. A.C. Guyton, J. Hall, Urine formation and the kidneys. Textbook of Medical Physiology, 9th edn. (WB Saunders, Philadelphia, 1996), pp. 332–335
3. R.D. Lawrence, Renal threshold for glucose: normal and in diabetics. Br. Med. J. 1(4140), 766–768 (1940)
4. R. DeFronzo, J. Davidson, S. Del Prato, The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes. Metab. 14(1), 5–14 (2012)
5. G. You, W.S. Lee, E.J. Barros, Y. Kanai, T.L. Huo, S. Khawaja, R.G. Wells, S.K. Nigam, M.A. Hediger, Molecular characteristics of Na(+)-coupled glucose transporters in adult and embryonic rat kidney. J. Biol. Chem. 270(49), 29365–29371 (1995)
6. G.L. Bakris, V.A. Fonseca, K. Sharma, E.M. Wright, Renal sodium–glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int. 75(12), 1272–1277 (2009)
7. R. Santer, J. Calado, Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin. J. Am. Soc. Nephrol. 5(1), 133–141 (2010). doi:10.2215/CJN.04010609
8. J. Calado, J. Loeffler, O. Sakallioglu, F. Gok, K. Lhotta, J. Barata, J. Rueff, Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Kidney Int. 69(5), 852–855 (2006)
9. E. Ottosson-Laakso, T. Tuomi, B. Forsén, M. Gullström, P.-H. Groop, L. Groop, P. Vikman, Influence of familial renal glycosuria due to mutations in the SLC5A2 gene on changes in glucose tolerance over time. PLoS ONE 11(1), e0146114 (2016)
10. A.T. Sands, B.P. Zambrowicz, J. Rosenstock, P. Lapuerta, B.W. Bode, S.K. Garg, J.B. Buse, P. Banks, R. Heptulla, M. Rendell, Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct therapy to insulin in type 1 diabetes. Diabetes Care 38(7), 1181–1188 (2015)
11. E. Ferrannini, S.J. Ramos, A. Salsali, W. Tang, J.F. List, 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 33(10), 2217–2224 (2010). doi:10.2337/dc10-0612
12. N. Inagaki, K. Kondo, T. Yoshinari, N. Maruyama, Y. Susuta, H. Kuki, Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes. Metab. 15(12), 1136–1145 (2013)
13. K. Stenlof, W.T. Cefalu, K.A. Kim, M. Alba, K. Usiskin, C. Tong, W. Canovatchel, G. Meininger, Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes. Metab. 15(4), 372–382 (2013). doi:10.1111/dom.12054
14. J. Rosenstock, M. Vico, L. Wei, A. Salsali, J.F. List, Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 35(7), 1473–1478 (2012). doi:10.2337/dc11-1693
15. J. Rosenstock, N. Aggarwal, D. Polidori, Y. Zhao, D. Arbit, K. Usiskin, G. Capuano, W. Canovatchel, Canagliflozin DIA 2001 Study Group, Dose-ranging effects of canagliflozin, a sodium–glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 35(6), 1232–1238 (2012)
16. C.J. Bailey, J.L. Gross, D. Hennicken, N. Iqbal, T.A. Mansfield, J.F. List, Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med. 11, 43 (2013). doi:10.1186/1741-7015-11-43
17. J.P. Wilding, G. Charpentier, P. Hollander, G. Gonzalez-Galvez, C. Mathieu, F. Vercruysse, K. Usiskin, G. Law, S. Black, W. Canovatchel, G. Meininger, Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int. J. Clin. Pract. 67(12), 1267–1282 (2013). doi:10.1111/ijcp.12322
18. J. Bolinder, Ö. Ljunggren, L. Johansson, J. Wilding, A. Langkilde, C. Sjöström, J. Sugg, S. Parikh, Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes. Metab. 16(2), 159–169 (2014)
19. J.P. Wilding, V. Woo, K. Rohwedder, J. Sugg, S. Parikh, Dapagliflozin 006 Study Group, Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes. Metab. 16(2), 124–136 (2014). doi:10.1111/dom.12187
20. E. Ferrannini, A. Berk, S. Hantel, S. Pinnetti, T. Hach, H.J. Woerle, U.C. Broedl, Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes. Diabetes Care 36(12), 4015–4021 (2013). doi:10.2337/dc13-0663
21. M. Ridderstråle, K.R. Andersen, C. Zeller, G. Kim, H.J. Woerle, U.C. Broedl, EMPA-REG H2H-SU trial investigators, Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2(9), 691–700 (2014)
22. S.E. Inzucchi, R.M. Bergenstal, J.B. Buse, M. Diamant, E. Ferrannini, M. Nauck, A.L. Peters, A. Tsapas, R. Wender, D.R. Matthews, Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38(1), 140–149 (2015). doi:10.2337/dc14-2441
23. T. Kadowaki, M. Haneda, N. Inagaki, Y. Terauchi, A. Taniguchi, K. Koiwai, H. Rattunde, H.J. Woerle, U.C. Broedl, Empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, 12-week, double-blind, placebo-controlled, phase II trial. Adv. Ther. 31(6), 621–638 (2014). doi:10.1007/s12325-014-0126-8
24. J. Bolinder, O. Ljunggren, J. Kullberg, L. Johansson, J. Wilding, A.M. Langkilde, J. Sugg, S. Parikh, 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. 97(3), 1020–1031 (2012). doi:10.1210/jc.2011-2260
25. G. Ferrannini, T. Hach, S. Crowe, A. Sanghvi, K.D. Hall, E. Ferrannini, Energy balance after sodium–glucose cotransporter 2 inhibition. Diabetes Care 38(9), 1730–1735 (2015). doi:10.2337/dc15-0355
26. D. Vasilakou, T. Karagiannis, E. Athanasiadou, M. Mainou, A. Liakos, E. Bekiari, M. Sarigianni, D.R. Matthews, A. Tsapas, Sodium–glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann. Intern. Med. 159(4), 262–274 (2013). doi:10.7326/0003-4819-159-4-201308200-00007
27. R. Chilton, I. Tikkanen, C.P. Cannon, S. Crowe, T. Hach, H.J. Woerle, U.C. Broedl, O.E. Johansen, 4b.02: the sodium glucose cotransporter 2 inhibitor empagliflozin reduces blood pressure and markers of arterial stiffness and vascular resistance in type 2 diabetes. J. Hypertens. 33(Suppl 1), e53 (2015). doi:10.1097/01.hjh.0000467486.05191.41
28. M.J. Davies, A. Trujillo, U. Vijapurkar, C.V. Damaraju, G. Meininger, Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus. Diabetes Obes. Metab. 17(4), 426–429 (2015). doi:10.1111/dom.12439
29. E. Hardy, A. Ptaszynska, T. de Bruin, E. Johnsson, S. Parikh, J. List, Changes in lipid profiles of patients with type 2 diabetes mellitus on dapagliflozin therapy. in Diabetologia, (Springer 233 Spring st, New York, NY 10013 USA, 2013), pp. S379–S379
30. J.F. Yale, G. Bakris, B. Cariou, D. Yue, E. David-Neto, L. Xi, K. Figueroa, E. Wajs, K. Usiskin, G. Meininger, Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes. Metab. 15(5), 463–473 (2013)
31. D.Z. Cherney, B.A. Perkins, N. Soleymanlou, M. Maione, V. Lai, A. Lee, N.M. Fagan, H.J. Woerle, O.E. Johansen, U.C. Broedl, M. von Eynatten, Renal hemodynamic effect of sodium–glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129(5), 587–597 (2014). doi:10.1161/CIRCULATIONAHA.113.005081
32. S.E. Inzucchi, B. Zinman, C. Wanner, R. Ferrari, D. Fitchett, S. Hantel, R.-M. Espadero, H.-J. Woerle, U.C. Broedl, O.E. Johansen, SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diabetes Vasc. Dis. Res. 12(2), 90–100 (2015)
33. N. Inagaki, K. Kondo, T. Yoshinari, H. Kuki, Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: a 52-week open-label study. J. Diabetes Investig. 6(2), 210–218 (2015)
34. H.J. Lambers Heerspink, D. de Zeeuw, L. Wie, B. Leslie, J. List, Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes. Metab. 15(9), 853–862 (2013). doi:10.1111/dom.12127
35. N. Erondu, M. Desai, K. Ways, G. Meininger, Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 38(9), 1680–1686 (2015). doi:10.2337/dc15-1251
36. S.I. Taylor, J.E. Blau, K.I. Rother, SGLT2 inhibitors may predispose to ketoacidosis. J. Clin. Endocrinol. Metab. 100(8), 2849–2852 (2015)
37. S.I. Taylor, J.E. Blau, K.I. Rother, Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 3(1), 8–10 (2015). doi:10.1016/S2213-8587(14)70227-X
38. B. Zinman, C. Wanner, J.M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O.E. Johansen, H.J. Woerle, U.C. Broedl, S.E. Inzucchi, E.-R.O. Investigators, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373(22), 2117–2128 (2015). doi:10.1056/NEJMoa1504720
39. J. McMurray, EMPA-REG-the “diuretic hypothesis”. J. Diabetes Complicat. 30(1), 3–4 (2015)
40. R.A. DeFronzo, The EMPA-REG study: what has it told us? a diabetologist’s perspective. J. Diabetes Complicat. 30(1), 1–2 (2016). doi:10.1016/j.jdiacomp.2015.10.013
41. P.D. Home, S.J. Pocock, H. Beck-Nielsen, R. Gomis, M. Hanefeld, N.P. Jones, M. Komajda, J.J. McMurray, Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N. Engl. J. Med. 357(1), 28–38 (2007)
42. S.E. Nissen, K. Wolski, Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356(24), 2457–2471 (2007). doi:10.1056/NEJMoa072761
43. A. Patel, ADVANCE Collaborative Group, S. MacMahon, J. Chalmers, B. Neal, M. Woodward, L. Billot, S. Harrap, N. Poulter, M. Marre, M. Cooper, P. Glasziou, D.E. Grobbee, P. Hamet, S. Heller, L.S. Liu, G. Mancia, C.E. Mogensen, C.Y. Pan, A. Rodgers, B. Williams, Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370(9590), 829–840 (2007). doi:10.1016/S0140-6736(07)61303-8
44. W. Duckworth, C. Abraira, T. Moritz, D. Reda, N. Emanuele, P.D. Reaven, F.J. Zieve, J. Marks, S.N. Davis, R. Hayward, S.R. Warren, S. Goldman, M. McCarren, M.E. Vitek, W.G. Henderson, G.D. Huang, VADT Investigators, Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 360(2), 129–139 (2009). doi:10.1056/NEJMoa0808431
45. R. Pop-Busui, G.W. Evans, H.C. Gerstein, V. Fonseca, J.L. Fleg, B.J. Hoogwerf, S. Genuth, R.H. Grimm, M.A. Corson, R. Prineas, Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 33(7), 1578–1584 (2010)
46. O.T. Investigators, H.C. Gerstein, J. Bosch, G.R. Dagenais, R. Diaz, H. Jung, A.P. Maggioni, J. Pogue, J. Probstfield, A. Ramachandran, M.C. Riddle, L.E. Ryden, S. Yusuf, Basal insulin and cardiovascular and other outcomes in dysglycemia. N. Engl. J. Med. 367(4), 319–328 (2012). doi:10.1056/NEJMoa1203858
47. W.B. White, C.P. Cannon, S.R. Heller, S.E. Nissen, R.M. Bergenstal, G.L. Bakris, A.T. Perez, P.R. Fleck, C.R. Mehta, S. Kupfer, C. Wilson, W.C. Cushman, F. Zannad, EXAMINE Investigators, Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369(14), 1327–1335 (2013). doi:10.1056/NEJMoa1305889
48. R. Bentley-Lewis, D. Aguilar, M.C. Riddle, B. Claggett, R. Diaz, K. Dickstein, H.C. Gerstein, P. Johnston, L.V. Kober, F. Lawson, E.F. Lewis, A.P. Maggioni, J.J. McMurray, L. Ping, J.L. Probstfield, S.D. Solomon, J.C. Tardif, Y. Wu, M.A. Pfeffer, EXAMINE Investigators, Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo. Am. Heart J. 169(5), 631–638 (2015). doi:10.1016/j.ahj.2015.02.002
49. J.B. Green, M.A. Bethel, P.W. Armstrong, J.B. Buse, S.S. Engel, J. Garg, R. Josse, K.D. Kaufman, J. Koglin, S. Korn, J.M. Lachin, D.K. McGuire, M.J. Pencina, E. Standl, P.P. Stein, S. Suryawanshi, F. Van de Werf, E.D. Peterson, R.R. Holman, TECOS Study Group, Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373(3), 232–242 (2015). doi:10.1056/NEJMoa1501352
50. J.A. Dormandy, B. Charbonnel, D.J. Eckland, E. Erdmann, M. Massi-Benedetti, I.K. Moules, A.M. Skene, M.H. Tan, P.J. Lefebvre, G.D. Murray, E. Standl, R.G. Wilcox, L. Wilhelmsen, J. Betteridge, K. Birkeland, A. Golay, R.J. Heine, L. Koranyi, M. Laakso, M. Mokan, A. Norkus, V. Pirags, T. Podar, A. Scheen, W. Scherbaum, G. Schernthaner, O. Schmitz, J. Skrha, U. Smith, J. Taton, PROactive investigators, Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366(9493), 1279–1289 (2005). doi:10.1016/S0140-6736(05)67528-9
51. S.E. Inzucchi, R.M. Bergenstal, J.B. Buse, M. Diamant, E. Ferrannini, M. Nauck, A.L. Peters, A. Tsapas, R. Wender, D.R. Matthews. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Update to a position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 58(3), 429–442 (2015)