Diabetes and its Complications and SGLT-2 Inhibitors: A Novel Therapy for Type 2 Diabetes Mellitus
Keywords:
SGLT2 inhibitors, dapagliflozin, sergliflozin, canagliflozin, remogliflozin, new antidiabetic drug
Abstract
The incidence of type 2 diabetes mellitus is increasing worldwide. The pharmacotherapy for type 2 diabetes until the last decade only consisted of biguanides, sulphonylureas, and insulin. The existing therapeutic classes of antidiabetic drugs are not adequately effective in maintaining long-term glycemic control in most patients, even when used in combination. One emerging novel therapeutic class of antidiabetic drugs is sodium glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 accounts for 90% of the glucose reabsorption in the kidney. The SGLT2 inhibitors increase urinary excretion of glucose and lower plasma glucose levels in an insulin-independent manner. Forxiga (Dapagliflozin) the most prominent molecule in this class is currently approved by USFDA. Other members of this class (eg, sergliflozin, remogliflozin) are also effective. This class of novel agents can effectively control blood sugar level without producing weight gain or hypoglycemia.
References
1.IDF diabetes atlas, international diabetes federation internet site. 2009, 4th edn October.
2.Amos A., Mccarty D. The rising global burden of diabetes and its complications: Estimates and projections to the year 2010. Diabetic med, 1987; 14: s1- s 85.
3.Geneva: WHO; 2005. Preventing chronic disease; a vital investment; WHO global report-2.
4.King H., Aubert R., Herman W. Global burden of diabetes, 1995-2025, prevalence, Numerical Estimates and Projections. Diabetes care, 1998; 21: 141-31.
5.WHO: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Department of non communicable disease Surveillance, Geneva, 1999.
6.Wild S., Roglic G., Green A., Sicreer., King H. Global prevalence of diabetes: Estimates of 2000 and Projections for 2030- Diabetes Care 2004 ; 27: 1047-53.
7.Stam D. M., Graham J. P. Important aspects of self management education in patients with Diabetes. Pharm. Pract Mange a. 1997; 17: 12-25.
8.Kuzuya, T., Nakagava S., Satoh,J., kanazawa Y., et al. Report of the committee on the Classification and diagnostic criteria of diabetes mellitus, Diabetes Research and Clinical Practice, 2004; 55: 65-85.
9.Satish K., Srivastava, Kota V. Ramana., Aruni Bhatnagar. Role of aldose reductase and oxidative damage in diabetes and consequent potential for therapeutic option. Endocrine Review 2005; 3: 380-392.
10.Prentki, M. Islet cell failure in type II diabetes. J. Clin Invest. 2006; 116: 1802-1812.
11.Biarnes M., Montolio M., Nacher V., Raurell M., Soler J., Montanya E. ß- cell death and mass in syngenically transplanted islets exposed to short and long term hyperglycemia.
12.U.K. prospective diabetes study 16. Overview of 6 years “therapy of type II diabetes: a Prospective disease study group. No authors listed diabetes. 1995; 44: 249-1258.
13.Douglas A., Martin J., Irina Obrosova., Eva L. Feldman. Glucose- induced oxidative stress and programmed cell death in diabetic neuropathy. European Journal of Pharmacology. 1999; 217-223.
14. American diabetes association (ADA): consensus development conference on insulin Resistance. Diabetes Care, 1998; 2:310-14.
15. Reaven G. M: Role of insulin resistance in human disease. Diabetes. 1988; 37: 1595- 609.
16. Kido Y., Burks D. J., et al. Tissue specific insulin resistance in mice with mutations in the insulin receptor, IRS-I and IRS-2. J. Clinical Invest, 2000; 105: 199-205.
17. Pessin J. E., Thurmond D. C., Elmendorf J. S et al. Molecular basis of insulin stimulated GLUT4 vesicle trafficking and location. J. Biol Chem. 1999; 274: 2593-96.
18. Hotamisligil G. S., peraldi P. IRS-I mediated inhibition of insulin receptor tyrosine kinase activity in TNF-a and obesity- induced insulin. 1996; 665-68.
19. Newgard insky F. M: In the Endocrine pancreas and regulation of metabolism, oxford university press, oxford 2001; 125-51.
20. Zhang C., Baffy G., perret p., et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, cell dysfunction, and type 2 diabetes. Cell,2001; 105: 745-55.
21. Horikawa Y., Oda N., Cox N. J., et al. Genetic variation in the gene encoding calpin 10 ispe 2 diabetes mellitus. Nat Genet. 2000; 26: 163-75.
22. Brajendra kumar., Arvind k. Diabetes mellitus; complications and therapeutics. Med. Sci Monit, 2006; 12, (7): RA 130-147.
23. Aiello L. P., Gardner T. W. Diabetic retinopathy. Diabetes care, 1998 ; 21:143-56.
24. Chen Y. D. Insulin resistance and atherosclerosis. Diabetes Rev, 2011; 5: 331-43.
25. Ritz E, Orth S. R. Nephropathy in patients with type 2 diabetes. N Engl J med, 1997; 341:1127-33.
26. Grundy S. M., Benjamin I. J., Burke G. L.,et al. Diabetes and cardiovascular disease. A statement for health care professionals from the American Heart Association, Circulation. 1999; 100: 1134-46.
27. Consensus development of conference on diabetic foot wound care, (American Diabetes Association, 7-8 April 1999; Boston) Diabetes Care 22: 1354-60.
28. Srivastava S. K., Ansari NH., Hair G. A., et al. Hyperglycemia induced activation of human erythrocyte aldose reductase and alterations in kinetic properties. Biochim Biophys Acta, 2001; 870, 302-11.
29. Isii H., Jirousek M. R., Koya D., et al. Amelioration of vascular dysfunctions in Diabetic rats by an oral PKC-ß inhibitor. Science, 1996; 272: 728-31.
30. Koya D., Handea M., Nakagawa H., et al. Amelioration of accelerated diabetic mesangal expansion by treatment with a PKC ß- inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. FASEB, 2000; 14: 439-47.
31. Kolm Litty V., Squer U., Nerlich A., et al. High glucose induced transforming growth factor betal production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J. Clin Invest, 1998; 101: 160-69.
32. Inzucchi, S.E. Oral antihyperglycemic therapy for type 2 DM. 2002; 287, 360 372.
33. Buse, J.B. et al. Effects of exendin-4 on glycemic control over 30 weeks in sulfonylurea’s treated with type 2 diabetes. Diabetes care 27. 2004; 2628-2635.
34. G. Perenz Lopez., O. Gonzalez., Albarran, M. Cano Megias. SGLT2 inhibitor: from renal glycosuria to the treatment of type 2 DM: Nefrologia 30, 2010; (6): 618-25.
35. Brown G. K. Glucose trasporters: structure, function and consequences of deficiency. J. Inherit Metab Dis 2000; 23: 237-246.
36. Wood I. S., Trayhurn P. Glucose trasporters (GLUT and SGLT): expanded families of sugar transport proteins. Br. J Nutr 2003; 89: 3-9.
37. Wright E. M., Loo D. D., Hirayama B. A., Turk E. Surprising versatility of Na+ glucose co-transporters: SLC5. Physiology(Bethesdo) 2004; 19: 370-376.
38. Turk E., Martin M. G. Wright EM. Structure of human Na+/ glucose cotrasporter gene SGLT1. J. Biol Chem 1994; 269: 15204-15209.
39. Wright E. M., Turk E. The sodium/ glucose cotrasporter family SLC5. Pflugers Arch 2004; 447: 510-518.
40. Wright E. M., Hirayama B. A., Loo D. F. Active sugar transport in health and disease. J. Intern Med 2007; 261:32-43.
41. Hirayama B. A., Lostao M. P., Panayotova Heiermann M., Loo D. D., turk E. Wright E. M. Kinetic and specificity differences between rat, human and rabbit Na+- glucose cotrasporters (SGLT-1) Am. J Physiol 1996; 270: G 919-G 926.
42. Kanai Y., Lee W. S., You G., Brown D., Hediger M. A. The human kidney low affinity Na+/glucose cotrasporter SGLT2. Delineation of major renal reabsorptive mechanism for D- glucose. J. Clin Invest 1994; 93: 397-404.
43. Elsas L. J., Rosenberg L. E. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J. Clin Invest 1969; 48: 1845-1854.
44. Santer R., Kinner M., et al. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J. Amsoc Nephrol 2003; 14: 2873-2882.
45. Vallon V., Platt K. A., Cunard R., Schroth J., Whaley J., Thomson S. C., Koepsell H., Rieg T. SGLT2 mediates glucoses reabsorption in the early proximal tubule. Am Soc Nephrol. 2011; 22: 104-112.
46. Dominguez J. H., Camp K., Maianu L., Feister H., Garvey W. T. Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats. Am J Physiol 1994; 266: F283-F290.
47. Rahmoune H., Thompson P. W., Ward J. M., Smith C. D., Hong G., Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54:3427-3434.
48. Kamran M., Peterson R. G., Dominguez J. H. Over expression of GLUT2 gene in renal proximal tubules of diabetic zucker rats. J Am Soc Nephrol 1997; 8: 943-948.
49. Gribble F. M., Williams L., Simpson A. K., Reimann F. A novel glucose- sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUT ag cell line. Diabetes 2003; 52:1147-1154.
50. Freitas H. S., Anhe G.F., Melo K. F., Okamoto M. M., Oliveira-Souza M., Bordin S., Machado U. F. Na+ glucose trasporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1 α expression and activity. Endocrinology 2008; 149: 717-724.
51. Yoojin Kim., Ambika R. Baby. Clinical potential of sodium- glucose cotrasporter 2 inhibitors in the management of type 2 diabetes. Diabetes, metabolic syndrome and obesity: Targets and Therapy 2012; 5: 313-327.
52. Farber S. J., Berger E. Y., Earle D. P. Effect of diabetes and insulin of the maximum capacity of the renal tubules to reabsorb glucose. J. Clin. Invest. 1951; 30: 125-129.
53. Rahmoune, H. et al. Glucose transporters in human renal proximal tubular cells Isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54: 3427-3434.
54. Edward C. Chao., Robert R. Henry. SGLT2 inhibition, a novel stratergy for diabetes treatment. Nature Review Drug Discovery/ AOP, Published online 28 may 2010; doi: 10. 1038/ nrd 3180.
55. Ehrenkranz, J. R., Lewis, N. G., Kahn. C. R., Roth J., Phlorizin:a review. Diabetes Metab.Res. Revs. 2005; 21: 31-38.
2.Amos A., Mccarty D. The rising global burden of diabetes and its complications: Estimates and projections to the year 2010. Diabetic med, 1987; 14: s1- s 85.
3.Geneva: WHO; 2005. Preventing chronic disease; a vital investment; WHO global report-2.
4.King H., Aubert R., Herman W. Global burden of diabetes, 1995-2025, prevalence, Numerical Estimates and Projections. Diabetes care, 1998; 21: 141-31.
5.WHO: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Department of non communicable disease Surveillance, Geneva, 1999.
6.Wild S., Roglic G., Green A., Sicreer., King H. Global prevalence of diabetes: Estimates of 2000 and Projections for 2030- Diabetes Care 2004 ; 27: 1047-53.
7.Stam D. M., Graham J. P. Important aspects of self management education in patients with Diabetes. Pharm. Pract Mange a. 1997; 17: 12-25.
8.Kuzuya, T., Nakagava S., Satoh,J., kanazawa Y., et al. Report of the committee on the Classification and diagnostic criteria of diabetes mellitus, Diabetes Research and Clinical Practice, 2004; 55: 65-85.
9.Satish K., Srivastava, Kota V. Ramana., Aruni Bhatnagar. Role of aldose reductase and oxidative damage in diabetes and consequent potential for therapeutic option. Endocrine Review 2005; 3: 380-392.
10.Prentki, M. Islet cell failure in type II diabetes. J. Clin Invest. 2006; 116: 1802-1812.
11.Biarnes M., Montolio M., Nacher V., Raurell M., Soler J., Montanya E. ß- cell death and mass in syngenically transplanted islets exposed to short and long term hyperglycemia.
12.U.K. prospective diabetes study 16. Overview of 6 years “therapy of type II diabetes: a Prospective disease study group. No authors listed diabetes. 1995; 44: 249-1258.
13.Douglas A., Martin J., Irina Obrosova., Eva L. Feldman. Glucose- induced oxidative stress and programmed cell death in diabetic neuropathy. European Journal of Pharmacology. 1999; 217-223.
14. American diabetes association (ADA): consensus development conference on insulin Resistance. Diabetes Care, 1998; 2:310-14.
15. Reaven G. M: Role of insulin resistance in human disease. Diabetes. 1988; 37: 1595- 609.
16. Kido Y., Burks D. J., et al. Tissue specific insulin resistance in mice with mutations in the insulin receptor, IRS-I and IRS-2. J. Clinical Invest, 2000; 105: 199-205.
17. Pessin J. E., Thurmond D. C., Elmendorf J. S et al. Molecular basis of insulin stimulated GLUT4 vesicle trafficking and location. J. Biol Chem. 1999; 274: 2593-96.
18. Hotamisligil G. S., peraldi P. IRS-I mediated inhibition of insulin receptor tyrosine kinase activity in TNF-a and obesity- induced insulin. 1996; 665-68.
19. Newgard insky F. M: In the Endocrine pancreas and regulation of metabolism, oxford university press, oxford 2001; 125-51.
20. Zhang C., Baffy G., perret p., et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, cell dysfunction, and type 2 diabetes. Cell,2001; 105: 745-55.
21. Horikawa Y., Oda N., Cox N. J., et al. Genetic variation in the gene encoding calpin 10 ispe 2 diabetes mellitus. Nat Genet. 2000; 26: 163-75.
22. Brajendra kumar., Arvind k. Diabetes mellitus; complications and therapeutics. Med. Sci Monit, 2006; 12, (7): RA 130-147.
23. Aiello L. P., Gardner T. W. Diabetic retinopathy. Diabetes care, 1998 ; 21:143-56.
24. Chen Y. D. Insulin resistance and atherosclerosis. Diabetes Rev, 2011; 5: 331-43.
25. Ritz E, Orth S. R. Nephropathy in patients with type 2 diabetes. N Engl J med, 1997; 341:1127-33.
26. Grundy S. M., Benjamin I. J., Burke G. L.,et al. Diabetes and cardiovascular disease. A statement for health care professionals from the American Heart Association, Circulation. 1999; 100: 1134-46.
27. Consensus development of conference on diabetic foot wound care, (American Diabetes Association, 7-8 April 1999; Boston) Diabetes Care 22: 1354-60.
28. Srivastava S. K., Ansari NH., Hair G. A., et al. Hyperglycemia induced activation of human erythrocyte aldose reductase and alterations in kinetic properties. Biochim Biophys Acta, 2001; 870, 302-11.
29. Isii H., Jirousek M. R., Koya D., et al. Amelioration of vascular dysfunctions in Diabetic rats by an oral PKC-ß inhibitor. Science, 1996; 272: 728-31.
30. Koya D., Handea M., Nakagawa H., et al. Amelioration of accelerated diabetic mesangal expansion by treatment with a PKC ß- inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. FASEB, 2000; 14: 439-47.
31. Kolm Litty V., Squer U., Nerlich A., et al. High glucose induced transforming growth factor betal production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J. Clin Invest, 1998; 101: 160-69.
32. Inzucchi, S.E. Oral antihyperglycemic therapy for type 2 DM. 2002; 287, 360 372.
33. Buse, J.B. et al. Effects of exendin-4 on glycemic control over 30 weeks in sulfonylurea’s treated with type 2 diabetes. Diabetes care 27. 2004; 2628-2635.
34. G. Perenz Lopez., O. Gonzalez., Albarran, M. Cano Megias. SGLT2 inhibitor: from renal glycosuria to the treatment of type 2 DM: Nefrologia 30, 2010; (6): 618-25.
35. Brown G. K. Glucose trasporters: structure, function and consequences of deficiency. J. Inherit Metab Dis 2000; 23: 237-246.
36. Wood I. S., Trayhurn P. Glucose trasporters (GLUT and SGLT): expanded families of sugar transport proteins. Br. J Nutr 2003; 89: 3-9.
37. Wright E. M., Loo D. D., Hirayama B. A., Turk E. Surprising versatility of Na+ glucose co-transporters: SLC5. Physiology(Bethesdo) 2004; 19: 370-376.
38. Turk E., Martin M. G. Wright EM. Structure of human Na+/ glucose cotrasporter gene SGLT1. J. Biol Chem 1994; 269: 15204-15209.
39. Wright E. M., Turk E. The sodium/ glucose cotrasporter family SLC5. Pflugers Arch 2004; 447: 510-518.
40. Wright E. M., Hirayama B. A., Loo D. F. Active sugar transport in health and disease. J. Intern Med 2007; 261:32-43.
41. Hirayama B. A., Lostao M. P., Panayotova Heiermann M., Loo D. D., turk E. Wright E. M. Kinetic and specificity differences between rat, human and rabbit Na+- glucose cotrasporters (SGLT-1) Am. J Physiol 1996; 270: G 919-G 926.
42. Kanai Y., Lee W. S., You G., Brown D., Hediger M. A. The human kidney low affinity Na+/glucose cotrasporter SGLT2. Delineation of major renal reabsorptive mechanism for D- glucose. J. Clin Invest 1994; 93: 397-404.
43. Elsas L. J., Rosenberg L. E. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J. Clin Invest 1969; 48: 1845-1854.
44. Santer R., Kinner M., et al. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J. Amsoc Nephrol 2003; 14: 2873-2882.
45. Vallon V., Platt K. A., Cunard R., Schroth J., Whaley J., Thomson S. C., Koepsell H., Rieg T. SGLT2 mediates glucoses reabsorption in the early proximal tubule. Am Soc Nephrol. 2011; 22: 104-112.
46. Dominguez J. H., Camp K., Maianu L., Feister H., Garvey W. T. Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats. Am J Physiol 1994; 266: F283-F290.
47. Rahmoune H., Thompson P. W., Ward J. M., Smith C. D., Hong G., Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54:3427-3434.
48. Kamran M., Peterson R. G., Dominguez J. H. Over expression of GLUT2 gene in renal proximal tubules of diabetic zucker rats. J Am Soc Nephrol 1997; 8: 943-948.
49. Gribble F. M., Williams L., Simpson A. K., Reimann F. A novel glucose- sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUT ag cell line. Diabetes 2003; 52:1147-1154.
50. Freitas H. S., Anhe G.F., Melo K. F., Okamoto M. M., Oliveira-Souza M., Bordin S., Machado U. F. Na+ glucose trasporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1 α expression and activity. Endocrinology 2008; 149: 717-724.
51. Yoojin Kim., Ambika R. Baby. Clinical potential of sodium- glucose cotrasporter 2 inhibitors in the management of type 2 diabetes. Diabetes, metabolic syndrome and obesity: Targets and Therapy 2012; 5: 313-327.
52. Farber S. J., Berger E. Y., Earle D. P. Effect of diabetes and insulin of the maximum capacity of the renal tubules to reabsorb glucose. J. Clin. Invest. 1951; 30: 125-129.
53. Rahmoune, H. et al. Glucose transporters in human renal proximal tubular cells Isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54: 3427-3434.
54. Edward C. Chao., Robert R. Henry. SGLT2 inhibition, a novel stratergy for diabetes treatment. Nature Review Drug Discovery/ AOP, Published online 28 may 2010; doi: 10. 1038/ nrd 3180.
55. Ehrenkranz, J. R., Lewis, N. G., Kahn. C. R., Roth J., Phlorizin:a review. Diabetes Metab.Res. Revs. 2005; 21: 31-38.
Published
2014-06-01
How to Cite
[1]
Kide, S., Kide, R., Thakare, L. and Ambulkar, K. 2014. Diabetes and its Complications and SGLT-2 Inhibitors: A Novel Therapy for Type 2 Diabetes Mellitus. PharmaTutor. 2, 6 (Jun. 2014), 75-94.
Section
Articles
