Drugs affecting the incretin system and renal glucose transport: do they meet the expectations of modern therapy of type 2 diabetes?
Anna Gumieniczek 1Abstract
Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of these drugs’ action, especially the long-term effects of their use. Most questionable is their impact on the processes of cell proliferation, on the cardiovascular and immune systems, on lipids and uric acid metabolism. A summary of the most important observations on the use of three groups of new drugs – analogs of glucagon-like peptide 1 (GLP-1), inhibitors of dipeptidyl peptidase IV (DPPIV) and inhibitors of sodium glucose cotransporters (SGLT1 and SGLT2) – has been made, based on a review of the literature over the past five years (2010-2014). The information included in the present review concerns the structure and activity relationship, therapeutic efficacy, side effects and the observed additional therapeutic effects, which can determine new standards in therapy of diabetes and also facilitate the development of better antidiabetic drugs.
References
- 1. Aroda V.R., Henry R.R., Han J., Huang W., DeYoung M.B., Darsow T.,Hoogwerf B.J.: Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors:meta-analysis and systematic review. Clin. Ther., 2012; 34: 1247-1258 2 Basile J.N.: The potential of sodium glucose cotransporter 2 (SGLT2)inhibitors to reduce cardiovascular risk in patients with type 2 diabetes(T2DM). J. Diabetes Complications, 2013; 27: 280-286
Google Scholar - 1. Aroda V.R., Henry R.R., Han J., Huang W., DeYoung M.B., Darsow T.,Hoogwerf B.J.: Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors:meta-analysis and systematic review. Clin. Ther., 2012; 34: 1247-1258 2 Basile J.N.: The potential of sodium glucose cotransporter 2 (SGLT2)inhibitors to reduce cardiovascular risk in patients with type 2 diabetes(T2DM). J. Diabetes Complications, 2013; 27: 280-286
Google Scholar - 2. diabetes. Diabetes Ther., 2011; 2: 133-145
Google Scholar - 2. diabetes. Diabetes Ther., 2011; 2: 133-145
Google Scholar - 3. Bhatt D.L., Cavender M.A.: Do dipeptidyl peptidase-4 inhibitors increasethe risk of heart failure? JACC Heart Fail., 2014; 2: 583-585 4 Bloomgarden Z.: Diabetes treatment: the coming paradigm shift. J.Diabetes, 2012; 4: 315-317
Google Scholar - 3. Bhatt D.L., Cavender M.A.: Do dipeptidyl peptidase-4 inhibitors increasethe risk of heart failure? JACC Heart Fail., 2014; 2: 583-585 4 Bloomgarden Z.: Diabetes treatment: the coming paradigm shift. J.Diabetes, 2012; 4: 315-317
Google Scholar - 4. w leczeniu cukrzycy typu 2. Terapia i Leki, 2010; 66: 55-61
Google Scholar - 4. w leczeniu cukrzycy typu 2. Terapia i Leki, 2010; 66: 55-61
Google Scholar - 5. Burcelin R., Thorens B., European Club for the Study of GLP-1 (EuCSGLP-1): Incretins: what is known, new and controversial in 2013? DiabetesMetab., 2013; 39: 89-93
Google Scholar - 5. Burcelin R., Thorens B., European Club for the Study of GLP-1 (EuCSGLP-1): Incretins: what is known, new and controversial in 2013? DiabetesMetab., 2013; 39: 89-93
Google Scholar - 6. Day J.W., Gelfanov V., Smiley D., Carrington P.E., Eiermann G., ChicchiG., Erion M.D., Gidda J., Thornberry N.A., Tschӧp M.H., Marsh D.J.,SinhaRoy R., DiMarchi R., Pocai A.: Optimization of co-agonism at GLP-1and glucagon receptors to safely maximize weight reduction in DIO–rodents. Biopolymers, 2012; 98: 443-450
Google Scholar - 6. Day J.W., Gelfanov V., Smiley D., Carrington P.E., Eiermann G., ChicchiG., Erion M.D., Gidda J., Thornberry N.A., Tschӧp M.H., Marsh D.J.,SinhaRoy R., DiMarchi R., Pocai A.: Optimization of co-agonism at GLP-1and glucagon receptors to safely maximize weight reduction in DIO–rodents. Biopolymers, 2012; 98: 443-450
Google Scholar - 7. Dimarchi R., Tao M.: Patent WO 2010/011439: GIP-based mixed agonistsfor treatment of metabolic disorders and obesity. 2010
Google Scholar - 7. Dimarchi R., Tao M.: Patent WO 2010/011439: GIP-based mixed agonistsfor treatment of metabolic disorders and obesity. 2010
Google Scholar - 8. Driessen J.H., van Onzenoort H.A., Henry R.M., Lalmohamed A., vanden Bergh JP., Neef C., Leufkens H.G., de Vries F.: Use of dipeptidyl peptidase- 4 inhibitors for type 2 diabetes mellitus and risk of fracture.Bone, 2014; 68: 124-130
Google Scholar - 8. Driessen J.H., van Onzenoort H.A., Henry R.M., Lalmohamed A., vanden Bergh JP., Neef C., Leufkens H.G., de Vries F.: Use of dipeptidyl peptidase- 4 inhibitors for type 2 diabetes mellitus and risk of fracture.Bone, 2014; 68: 124-130
Google Scholar - 9. Filipek B.: Miejsce inkretynomimetykow i inhibitorów dipeptydylopeptydazy
Google Scholar - 9. Filipek B.: Miejsce inkretynomimetykow i inhibitorów dipeptydylopeptydazy
Google Scholar - 10. Fonseca V.A.: New developments in diabetes management: medicationsof the 21st century. Clin. Ther., 2014; 36: 477-484
Google Scholar - 10. Fonseca V.A.: New developments in diabetes management: medicationsof the 21st century. Clin. Ther., 2014; 36: 477-484
Google Scholar - 11. Green J.B., Bethel M.A., Paul S.K., Ring A., Kaufman K.D., ShapiroD.R., Califf R.M., Holman R.R.: Rationale, design, and organization ofa randomized, controlled Trial Evaluating Cardiovascular Outcomeswith Sitagliptin (TECOS) in patients with type 2 diabetes and establishedcardiovascular disease. Am. Heart J., 2013; 166: 983-989.e7
Google Scholar - 11. Green J.B., Bethel M.A., Paul S.K., Ring A., Kaufman K.D., ShapiroD.R., Califf R.M., Holman R.R.: Rationale, design, and organization ofa randomized, controlled Trial Evaluating Cardiovascular Outcomeswith Sitagliptin (TECOS) in patients with type 2 diabetes and establishedcardiovascular disease. Am. Heart J., 2013; 166: 983-989.e7
Google Scholar - 12. Hamilton B., Herring C., Paulik M.: Patent WO 2011/039096: Drugfusions and conjugates with extended half life. 2011
Google Scholar - 12. Hamilton B., Herring C., Paulik M.: Patent WO 2011/039096: Drugfusions and conjugates with extended half life. 2011
Google Scholar - 13. Hardman T.C., Dubrey S.W.: Development and potential role oftype-2 sodium-glucose transporter inhibitors for management of type
Google Scholar - 13. Hardman T.C., Dubrey S.W.: Development and potential role oftype-2 sodium-glucose transporter inhibitors for management of type
Google Scholar - 14. Hasan F.M., Alsahli M., Gerich J.E.: SGLT2 inhibitors in the treatmentof type 2 diabetes. Diabetes Res. Clin. Pract., 2014; 104: 297-322
Google Scholar - 14. Hasan F.M., Alsahli M., Gerich J.E.: SGLT2 inhibitors in the treatmentof type 2 diabetes. Diabetes Res. Clin. Pract., 2014; 104: 297-322
Google Scholar - 15. Inzucchi S.E., Bergenstal R.M., Buse J.B., Diamant M., Ferrannini E.,Nauck M., Peters A.L., Tsapas A., Wender R., Matthews D.R.: Managementof hyperglycemia in type 2 diabetes, 2015: a patient-centeredapproach: update to a position statement of the American DiabetesAssociation and the European Association for the Study of Diabetes.Diabetes Care, 2015; 38: 140-149
Google Scholar - 15. Inzucchi S.E., Bergenstal R.M., Buse J.B., Diamant M., Ferrannini E.,Nauck M., Peters A.L., Tsapas A., Wender R., Matthews D.R.: Managementof hyperglycemia in type 2 diabetes, 2015: a patient-centeredapproach: update to a position statement of the American DiabetesAssociation and the European Association for the Study of Diabetes.Diabetes Care, 2015; 38: 140-149
Google Scholar - 16. Jayawardene D., Ward G.M., O´Neal D.N., Theverkalam G., MacIsaacA.I., MacIsaac R.J.: New treatments for type 2 diabetes: cardiovascularprotection beyond glucose lowering? Heart Lung Circ., 2014; 23: 997-1008
Google Scholar - 16. Jayawardene D., Ward G.M., O´Neal D.N., Theverkalam G., MacIsaacA.I., MacIsaac R.J.: New treatments for type 2 diabetes: cardiovascularprotection beyond glucose lowering? Heart Lung Circ., 2014; 23: 997-1008
Google Scholar - 17. Kumar K.V., Gupta A.K.: Clinical audit of patients using DPP4 inhibitorsin longstanding type 2 diabetes. Diabetes Metab. Syndr., 2015;9: 277-279
Google Scholar - 17. Kumar K.V., Gupta A.K.: Clinical audit of patients using DPP4 inhibitorsin longstanding type 2 diabetes. Diabetes Metab. Syndr., 2015;9: 277-279
Google Scholar - 18. Kurosaki E., Ogasawara H.: Ipragliflozin and other sodium–glucosecotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes:preclinical and clinical data. Pharmacol. Ther., 2013; 139: 51-59
Google Scholar - 18. Kurosaki E., Ogasawara H.: Ipragliflozin and other sodium–glucosecotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes:preclinical and clinical data. Pharmacol. Ther., 2013; 139: 51-59
Google Scholar - 19. Lorenz M., Evers A., Wagner M.: Recent progress and future optionsin the developments of GLP-1 receptor agonists for the treatment ofdiabesity, Bioorg. Med. Chem. Lett., 2013; 23: 4011-4018
Google Scholar - 19. Lorenz M., Evers A., Wagner M.: Recent progress and future optionsin the developments of GLP-1 receptor agonists for the treatment ofdiabesity, Bioorg. Med. Chem. Lett., 2013; 23: 4011-4018
Google Scholar - 20. Lund A., Knop F.K., Vilsboll T.: Glucagon-like peptide-1 receptoragonists for the treatment of type 2 diabetes: differences and similarities.Eur. J. Intern. Med., 2014: 25: 407-414
Google Scholar - 20. Lund A., Knop F.K., Vilsboll T.: Glucagon-like peptide-1 receptoragonists for the treatment of type 2 diabetes: differences and similarities.Eur. J. Intern. Med., 2014: 25: 407-414
Google Scholar - 21. Łabuzek K., Kozłowski M., Szkudłapski D., Sikorska P., Kozłowska M.,Okopień B.: Incretin-based therapies in the treatment of type 2 diabetes– more than meets the eye? Eur. J. Intern. Med., 2013; 24: 207-212
Google Scholar - 21. Łabuzek K., Kozłowski M., Szkudłapski D., Sikorska P., Kozłowska M.,Okopień B.: Incretin-based therapies in the treatment of type 2 diabetes– more than meets the eye? Eur. J. Intern. Med., 2013; 24: 207-212
Google Scholar - 22. Monami M., Dicembrini I., Mannucci E.: Dipeptidyl peptidase-4 inhibitorsand heart failure: a meta-analysis of randomized clinical trials.Nutr. Metab. Cardiovasc. Dis., 2014; 24: 689-697
Google Scholar - 22. Monami M., Dicembrini I., Mannucci E.: Dipeptidyl peptidase-4 inhibitorsand heart failure: a meta-analysis of randomized clinical trials.Nutr. Metab. Cardiovasc. Dis., 2014; 24: 689-697
Google Scholar - 23. Monami M., Dicembrini I., Nardini C., Fiordelli I., Mannucci E.: Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysisof randomized clinical trials. Diabetes Res. Clin. Pract., 2014; 103: 269-275
Google Scholar - 23. Monami M., Dicembrini I., Nardini C., Fiordelli I., Mannucci E.: Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysisof randomized clinical trials. Diabetes Res. Clin. Pract., 2014; 103: 269-275
Google Scholar - 24. Patil H.R., Al Badarin F.J., Al Shami H.A., Bhatti S.K., Lavie C.J., BellD.S., O´Keefe J.H.: Meta-analysis of effect of dipeptidyl peptidase-4 inhibitorson cardiovascular risk in type 2 diabetes mellitus. Am. J. Cardiol.,2012; 110: 826-833
Google Scholar - 24. Patil H.R., Al Badarin F.J., Al Shami H.A., Bhatti S.K., Lavie C.J., BellD.S., O´Keefe J.H.: Meta-analysis of effect of dipeptidyl peptidase-4 inhibitorson cardiovascular risk in type 2 diabetes mellitus. Am. J. Cardiol.,2012; 110: 826-833
Google Scholar - 25. Przybysławski B., Karbowiak P., Rzeszotarski J., Walasek L.: Inhibitorykotransportera glukozowo-sodowego 2 (SGLT2): nowa grupa doustnychleków przeciwcukrzycowych. Diabetol. Klin., 2013: 2: 191-197
Google Scholar - 25. Przybysławski B., Karbowiak P., Rzeszotarski J., Walasek L.: Inhibitorykotransportera glukozowo-sodowego 2 (SGLT2): nowa grupa doustnychleków przeciwcukrzycowych. Diabetol. Klin., 2013: 2: 191-197
Google Scholar - 26. Santoprete A., Capitò E., Carrington P.E., Pocai A., Finotto M., LangellaA., Ingalinella P., Zytko K., Bufali S., Cianetti S., Veneziano M., BonelliF., Zhu L., Monteagudo E., Marsh D.J., Sinharoy R., Bianci E., PessiA.: DPP-IV-resistant, long-acting oxyntomodulin derivatives. J. Pept.Sci., 2011; 17: 270-280
Google Scholar - 26. Santoprete A., Capitò E., Carrington P.E., Pocai A., Finotto M., LangellaA., Ingalinella P., Zytko K., Bufali S., Cianetti S., Veneziano M., BonelliF., Zhu L., Monteagudo E., Marsh D.J., Sinharoy R., Bianci E., PessiA.: DPP-IV-resistant, long-acting oxyntomodulin derivatives. J. Pept.Sci., 2011; 17: 270-280
Google Scholar - 27. Sciacca L., Vigneri R., Tumminia A., Frasca F., Squatrito S., FrittittaL., Vigneri P.: Clinical and molecular mechanisms favoring cancer initiationand progression in diabetic patients. Nutr. Metab. Cardiovasc.Dis., 2013; 23: 808-815
Google Scholar - 27. Sciacca L., Vigneri R., Tumminia A., Frasca F., Squatrito S., FrittittaL., Vigneri P.: Clinical and molecular mechanisms favoring cancer initiationand progression in diabetic patients. Nutr. Metab. Cardiovasc.Dis., 2013; 23: 808-815
Google Scholar - 28. Spranger J., Gundert-Remy U., Stammschulte T.: GLP-1 based therapies:the dilemma of uncertainty. Gastroenterology, 2011; 141: 20-23
Google Scholar - 28. Spranger J., Gundert-Remy U., Stammschulte T.: GLP-1 based therapies:the dilemma of uncertainty. Gastroenterology, 2011; 141: 20-23
Google Scholar - 29. Steinhilber D., Schubert-Zsilavecz M., Roth H.J.: Chemia Medyczna,MedPharm. Polska, Wrocław 2012
Google Scholar - 29. Steinhilber D., Schubert-Zsilavecz M., Roth H.J.: Chemia Medyczna,MedPharm. Polska, Wrocław 2012
Google Scholar - 30. Verma R.: Canagliflozin-associated acute pancreatitis. Am. J. Ther., 2014 (w druku)
Google Scholar - 30. Verma R.: Canagliflozin-associated acute pancreatitis. Am. J. Ther., 2014 (w druku)
Google Scholar - 31. Vest A.R.: Incretin-related drug therapy in heart failure. Curr. HeartFail. Rep., 2015; 12: 24-32
Google Scholar - 31. Vest A.R.: Incretin-related drug therapy in heart failure. Curr. HeartFail. Rep., 2015; 12: 24-32
Google Scholar