Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2013

Open Access 01-12-2013 | Review

The cardiovascular safety of incretin-based therapies: a review of the evidence

Author: John R Petrie

Published in: Cardiovascular Diabetology | Issue 1/2013

Login to get access

Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in people with diabetes and therefore managing cardiovascular (CV) risk is a critical component of diabetes care. As incretin-based therapies are effective recent additions to the glucose-lowering treatment armamentarium for type 2 diabetes mellitus (T2D), understanding their CV safety profiles is of great importance. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with beneficial effects on CV risk factors, including weight, blood pressure and lipid profiles. Encouragingly, mechanistic studies in preclinical models and in patients with acute coronary syndrome suggest a potential cardioprotective effect of native GLP-1 or GLP-1 receptor agonists following ischaemia. Moreover, meta-analyses of phase 3 development programme data indicate no increased risk of major adverse cardiovascular events (MACE) with incretin-based therapies. Large randomized controlled trials designed to evaluate long-term CV outcomes with incretin-based therapies in individuals with T2D are now in progress, with the first two reporting as this article went to press.
Appendix
Available only for authorised users
Literature
2.
go back to reference Mak KH, Moliterno DJ, Granger CB, Miller DP, White HD, Wilcox RG, Califf RM, Topol EJ, for the GUSTO-I Investigators: Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. J Am Coll Cardiol. 1997, 30: 171-179. 10.1016/S0735-1097(97)00118-6.PubMedCrossRef Mak KH, Moliterno DJ, Granger CB, Miller DP, White HD, Wilcox RG, Califf RM, Topol EJ, for the GUSTO-I Investigators: Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. J Am Coll Cardiol. 1997, 30: 171-179. 10.1016/S0735-1097(97)00118-6.PubMedCrossRef
3.
go back to reference Lind M, Garcia-Rodriguez LA, Booth GL, Cea-Soriano L, Shah BR, Ekeroth G, Lipscombe LL: Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study. Diabetologia. 2013, 10.1007/s00125-013-2949-2. Lind M, Garcia-Rodriguez LA, Booth GL, Cea-Soriano L, Shah BR, Ekeroth G, Lipscombe LL: Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study. Diabetologia. 2013, 10.1007/s00125-013-2949-2.
4.
go back to reference Aryangat AV, Gerich JE: Type 2 diabetes: postprandial hyperglycemia and increased cardiovascular risk. Vasc Health Risk Manag. 2010, 6: 145-155.PubMedCentralPubMed Aryangat AV, Gerich JE: Type 2 diabetes: postprandial hyperglycemia and increased cardiovascular risk. Vasc Health Risk Manag. 2010, 6: 145-155.PubMedCentralPubMed
5.
go back to reference Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000, 321 (7258): 405-412. 10.1136/bmj.321.7258.405.PubMedCentralPubMedCrossRef Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000, 321 (7258): 405-412. 10.1136/bmj.321.7258.405.PubMedCentralPubMedCrossRef
6.
go back to reference Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH, Byington RP, Rosenberg YD, Friedewald WT, ACCORD Study Group: Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011, 364 (9): 818-828.PubMedCrossRef Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH, Byington RP, Rosenberg YD, Friedewald WT, ACCORD Study Group: Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011, 364 (9): 818-828.PubMedCrossRef
7.
go back to reference Singh S, Loke YK, Furberg CD: Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care. 2007, 30: 2148-2153. 10.2337/dc07-0141.PubMedCrossRef Singh S, Loke YK, Furberg CD: Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care. 2007, 30: 2148-2153. 10.2337/dc07-0141.PubMedCrossRef
8.
go back to reference Singh S, Loke YK, Furberg CD: Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007, 298: 1189-1195. 10.1001/jama.298.10.1189.PubMedCrossRef Singh S, Loke YK, Furberg CD: Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007, 298: 1189-1195. 10.1001/jama.298.10.1189.PubMedCrossRef
10.
go back to reference Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, Ali F, Sholley C, Worrall C, Kelman JA: Risk of acute myocardial infarction, stroke, heart failure, and death in elderly medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010, 304: 411-418. 10.1001/jama.2010.920.PubMedCrossRef Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, Ali F, Sholley C, Worrall C, Kelman JA: Risk of acute myocardial infarction, stroke, heart failure, and death in elderly medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010, 304: 411-418. 10.1001/jama.2010.920.PubMedCrossRef
12.
go back to reference White J: Efficacy and safety of incretin based therapies: clinical trial data. Assoc J Am Pharm (2003). 2009, 49 (1): S30-S40.CrossRef White J: Efficacy and safety of incretin based therapies: clinical trial data. Assoc J Am Pharm (2003). 2009, 49 (1): S30-S40.CrossRef
13.
go back to reference Jellinger PS: Focus on incretin-based therapies: targeting the core defects of type 2 diabetes. Postgrad Med. 2011, 123: 53-65. 10.3810/pgm.2011.01.2245.PubMedCrossRef Jellinger PS: Focus on incretin-based therapies: targeting the core defects of type 2 diabetes. Postgrad Med. 2011, 123: 53-65. 10.3810/pgm.2011.01.2245.PubMedCrossRef
15.
go back to reference Ray KK, Petrie J, Bengus M, Bengus M, Ekman S, Dixon M, Herz M, Buse J: Individual participant meta analysis of the cardiovascular safety of taspoglutide among individuals with diabetes. Circulation. 2012, 126 (21 Suppl): A15282 Ray KK, Petrie J, Bengus M, Bengus M, Ekman S, Dixon M, Herz M, Buse J: Individual participant meta analysis of the cardiovascular safety of taspoglutide among individuals with diabetes. Circulation. 2012, 126 (21 Suppl): A15282
22.
go back to reference Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desal NR, Mozenson O, McGuire DK, Ray KK, Leiter LA, Raz I, the SAVOR-TIMI 53 Steering Committee and Investigators: Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013, 10.1053/NEJMoa1307684. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desal NR, Mozenson O, McGuire DK, Ray KK, Leiter LA, Raz I, the SAVOR-TIMI 53 Steering Committee and Investigators: Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013, 10.1053/NEJMoa1307684.
24.
go back to reference White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris G, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F, the EXAMINE Investigators: Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013, 10.1056/NEJMoa1305889. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris G, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F, the EXAMINE Investigators: Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013, 10.1056/NEJMoa1305889.
26.
go back to reference Baggio LL, Drucker DJ: Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007, 132: 2131-2157. 10.1053/j.gastro.2007.03.054.PubMedCrossRef Baggio LL, Drucker DJ: Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007, 132: 2131-2157. 10.1053/j.gastro.2007.03.054.PubMedCrossRef
27.
go back to reference Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsbøll T: Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011, 96: 737-745. 10.1210/jc.2010-2435.PubMedCrossRef Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsbøll T: Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011, 96: 737-745. 10.1210/jc.2010-2435.PubMedCrossRef
28.
go back to reference Nauck M, Stöckmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986, 29: 46-52. 10.1007/BF02427280.PubMedCrossRef Nauck M, Stöckmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986, 29: 46-52. 10.1007/BF02427280.PubMedCrossRef
29.
go back to reference Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W: Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993, 91: 301-307. 10.1172/JCI116186.PubMedCentralPubMedCrossRef Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W: Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993, 91: 301-307. 10.1172/JCI116186.PubMedCentralPubMedCrossRef
30.
go back to reference Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001, 50: 609-613. 10.2337/diabetes.50.3.609.PubMedCrossRef Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001, 50: 609-613. 10.2337/diabetes.50.3.609.PubMedCrossRef
31.
go back to reference Nauck MA, Vardarli I, Deacon CF, Holst JJ, Meier JJ: Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?. Diabetologia. 2011, 54 (1): 10-18. 10.1007/s00125-010-1896-4.PubMedCrossRef Nauck MA, Vardarli I, Deacon CF, Holst JJ, Meier JJ: Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?. Diabetologia. 2011, 54 (1): 10-18. 10.1007/s00125-010-1896-4.PubMedCrossRef
32.
go back to reference Larsen J, Hylleberg B, Ng K, Damsbo P: Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment. Diabetes Care. 2001, 24: 1416-1421. 10.2337/diacare.24.8.1416.PubMedCrossRef Larsen J, Hylleberg B, Ng K, Damsbo P: Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment. Diabetes Care. 2001, 24: 1416-1421. 10.2337/diacare.24.8.1416.PubMedCrossRef
35.
go back to reference Vila Petroff MG, Egan JM, Wang X, Sollott SJ: Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res. 2001, 89: 445-452. 10.1161/hh1701.095716.PubMedCrossRef Vila Petroff MG, Egan JM, Wang X, Sollott SJ: Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res. 2001, 89: 445-452. 10.1161/hh1701.095716.PubMedCrossRef
36.
go back to reference Gros R, You X, Baggio LL, Kabir MG, Sadi AM, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M: Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology. 2003, 144: 2242-2252. 10.1210/en.2003-0007.PubMedCrossRef Gros R, You X, Baggio LL, Kabir MG, Sadi AM, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M: Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology. 2003, 144: 2242-2252. 10.1210/en.2003-0007.PubMedCrossRef
37.
go back to reference Anagnostis P, Athyros VG, Adamidou F, Panagiotou A, Kita M, Karagiannis A, Mikhailidis DP: Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control. Diab Obes Metab. 2011, 13: 302-312. 10.1111/j.1463-1326.2010.01345.x.CrossRef Anagnostis P, Athyros VG, Adamidou F, Panagiotou A, Kita M, Karagiannis A, Mikhailidis DP: Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control. Diab Obes Metab. 2011, 13: 302-312. 10.1111/j.1463-1326.2010.01345.x.CrossRef
38.
go back to reference Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M: Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008, 117: 2340-2350. 10.1161/CIRCULATIONAHA.107.739938.PubMedCrossRef Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M: Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008, 117: 2340-2350. 10.1161/CIRCULATIONAHA.107.739938.PubMedCrossRef
39.
go back to reference Wei Y, Mojsov S: Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995, 358: 219-224. 10.1016/0014-5793(94)01430-9.PubMedCrossRef Wei Y, Mojsov S: Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995, 358: 219-224. 10.1016/0014-5793(94)01430-9.PubMedCrossRef
40.
go back to reference Erdogdu O, Nathanson D, Sjöholm A, Nyström T, Zhang Q: Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor. Mol Cell Endocrinol. 2010, 325 (1–2): 26-35.PubMedCrossRef Erdogdu O, Nathanson D, Sjöholm A, Nyström T, Zhang Q: Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor. Mol Cell Endocrinol. 2010, 325 (1–2): 26-35.PubMedCrossRef
41.
go back to reference Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP: Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004, 109: 962-965. 10.1161/01.CIR.0000120505.91348.58.PubMedCrossRef Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP: Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004, 109: 962-965. 10.1161/01.CIR.0000120505.91348.58.PubMedCrossRef
42.
go back to reference Treiman M, Elvekjaer M, Engstrøm T, Jensen JS: Glucagon-like peptide 1 – a cardiologic dimension. Trends Cardiovasc Med. 2010, 20: 8-12. 10.1016/j.tcm.2010.02.012.PubMedCrossRef Treiman M, Elvekjaer M, Engstrøm T, Jensen JS: Glucagon-like peptide 1 – a cardiologic dimension. Trends Cardiovasc Med. 2010, 20: 8-12. 10.1016/j.tcm.2010.02.012.PubMedCrossRef
43.
go back to reference Nyström T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, Sjöholm A: Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004, 287 (6): E1209-E1215. 10.1152/ajpendo.00237.2004.PubMedCrossRef Nyström T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, Sjöholm A: Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004, 287 (6): E1209-E1215. 10.1152/ajpendo.00237.2004.PubMedCrossRef
44.
go back to reference Sjöholm A: Impact of glucagon-like peptide-1 on endothelial function. Diab Obes Metab. 2009, 11 (Suppl 3): 19-25.CrossRef Sjöholm A: Impact of glucagon-like peptide-1 on endothelial function. Diab Obes Metab. 2009, 11 (Suppl 3): 19-25.CrossRef
45.
go back to reference Logue J, Walker JJ, Leese G, Lindsay R, McKnight J, Morris A, Philip S, Wild S, Sattar N, on behalf of The Scottish Diabetes Research Network Epidemiology Group: The association between BMI measured within a year after diagnosis of type 2 diabetes and mortality. Diabetes Care. 2012, 36 (4): 887-893.PubMedCrossRef Logue J, Walker JJ, Leese G, Lindsay R, McKnight J, Morris A, Philip S, Wild S, Sattar N, on behalf of The Scottish Diabetes Research Network Epidemiology Group: The association between BMI measured within a year after diagnosis of type 2 diabetes and mortality. Diabetes Care. 2012, 36 (4): 887-893.PubMedCrossRef
47.
go back to reference Ratner R, Goldberg R, Haffner S, Marcovina S, Orchard T, Fowler S, Temprosa M, Diabetes Prevention Program Research Group: Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care. 2005, 28: 888-894.PubMedCrossRef Ratner R, Goldberg R, Haffner S, Marcovina S, Orchard T, Fowler S, Temprosa M, Diabetes Prevention Program Research Group: Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care. 2005, 28: 888-894.PubMedCrossRef
48.
go back to reference Horton ES, Silberman C, Davis KL, Berria R: Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010, 33: 1759-1765. 10.2337/dc09-2062.PubMedCentralPubMedCrossRef Horton ES, Silberman C, Davis KL, Berria R: Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010, 33: 1759-1765. 10.2337/dc09-2062.PubMedCentralPubMedCrossRef
49.
go back to reference Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P, Sitagliptin Study 019 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006, 28: 1556-1568. 10.1016/j.clinthera.2006.10.007.PubMedCrossRef Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P, Sitagliptin Study 019 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006, 28: 1556-1568. 10.1016/j.clinthera.2006.10.007.PubMedCrossRef
50.
go back to reference Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE, Sitagliptin 036 Study Group: Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007, 30: 1979-1987. 10.2337/dc07-0627.PubMedCrossRef Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE, Sitagliptin 036 Study Group: Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007, 30: 1979-1987. 10.2337/dc07-0627.PubMedCrossRef
51.
go back to reference Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP, Sitagliptin Study 024 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007, 9: 194-205. 10.1111/j.1463-1326.2006.00704.x.PubMedCrossRef Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP, Sitagliptin Study 024 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007, 9: 194-205. 10.1111/j.1463-1326.2006.00704.x.PubMedCrossRef
52.
go back to reference Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P, Sitagliptin Study 035 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diab Obes Metab. 2007, 9 (5): 733-745. 10.1111/j.1463-1326.2007.00744.x.CrossRef Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P, Sitagliptin Study 035 Group: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diab Obes Metab. 2007, 9 (5): 733-745. 10.1111/j.1463-1326.2007.00744.x.CrossRef
53.
go back to reference Rosenstock J, Sankoh S, List JF: Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diab Obes Metab. 2008, 10: 376-386. 10.1111/j.1463-1326.2008.00876.x.CrossRef Rosenstock J, Sankoh S, List JF: Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diab Obes Metab. 2008, 10: 376-386. 10.1111/j.1463-1326.2008.00876.x.CrossRef
54.
go back to reference Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, CHen R, CV181-040 Investigators: Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract. 2009, 63: 1395-1406. 10.1111/j.1742-1241.2009.02143.x.PubMedCentralPubMedCrossRef Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, CHen R, CV181-040 Investigators: Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract. 2009, 63: 1395-1406. 10.1111/j.1742-1241.2009.02143.x.PubMedCentralPubMedCrossRef
55.
go back to reference DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS, Saxagliptin 014 Study Group: The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009, 32: 1649-1655. 10.2337/dc08-1984.PubMedCentralPubMedCrossRef DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS, Saxagliptin 014 Study Group: The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009, 32: 1649-1655. 10.2337/dc08-1984.PubMedCentralPubMedCrossRef
56.
go back to reference Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R, CV181-039 Investigators: Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diab Obes Metab. 2009, 11: 611-622. 10.1111/j.1463-1326.2009.01056.x.CrossRef Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R, CV181-039 Investigators: Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diab Obes Metab. 2009, 11: 611-622. 10.1111/j.1463-1326.2009.01056.x.CrossRef
57.
go back to reference Mathieu C, Degrande E: Vildagliptin: a new oral treatment for type 2 diabetes mellitus. Vasc Health Risk Manag. 2008, 4: 1349-1360.PubMedCentralPubMed Mathieu C, Degrande E: Vildagliptin: a new oral treatment for type 2 diabetes mellitus. Vasc Health Risk Manag. 2008, 4: 1349-1360.PubMedCentralPubMed
58.
go back to reference DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005, 28: 1092-1100. 10.2337/diacare.28.5.1092.PubMedCrossRef DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005, 28: 1092-1100. 10.2337/diacare.28.5.1092.PubMedCrossRef
59.
go back to reference Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD, Exenatide-113 Clinical Study Group: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004, 27: 2628-2635. 10.2337/diacare.27.11.2628.PubMedCrossRef Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD, Exenatide-113 Clinical Study Group: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004, 27: 2628-2635. 10.2337/diacare.27.11.2628.PubMedCrossRef
60.
go back to reference Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005, 28: 1083-1091. 10.2337/diacare.28.5.1083.PubMedCrossRef Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005, 28: 1083-1091. 10.2337/diacare.28.5.1083.PubMedCrossRef
61.
go back to reference Drucker DJ, Buse JB, Taylor K, Trautmann M, Zhuang D, Porter L, DURATION-1 Study Group: Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008, 372 (9645): 1240-1250. 10.1016/S0140-6736(08)61206-4.PubMedCrossRef Drucker DJ, Buse JB, Taylor K, Trautmann M, Zhuang D, Porter L, DURATION-1 Study Group: Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008, 372 (9645): 1240-1250. 10.1016/S0140-6736(08)61206-4.PubMedCrossRef
62.
go back to reference Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE, DURATION-2 Study Group: Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010, 376 (9739): 431-439. 10.1016/S0140-6736(10)60590-9.PubMedCrossRef Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE, DURATION-2 Study Group: Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010, 376 (9739): 431-439. 10.1016/S0140-6736(10)60590-9.PubMedCrossRef
63.
go back to reference Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M: Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010, 375 (9733): 2234-2243. 10.1016/S0140-6736(10)60406-0.PubMedCrossRef Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M: Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010, 375 (9733): 2234-2243. 10.1016/S0140-6736(10)60406-0.PubMedCrossRef
64.
go back to reference Boardman MK, Hanefeld M, Kumar A, Gonzalez JG, de Teresa L, Northrup J, Chan M, Russell-Jones DL: DURATION-4: improvements in glucose control and cardiovascular risk factors in patients with type 2 diabetes treated with exenatide once weekly, metformin, pioglitazone, or sitagliptin. Diabetologia. 2011, 54 (1): S314-Abstract 779 Boardman MK, Hanefeld M, Kumar A, Gonzalez JG, de Teresa L, Northrup J, Chan M, Russell-Jones DL: DURATION-4: improvements in glucose control and cardiovascular risk factors in patients with type 2 diabetes treated with exenatide once weekly, metformin, pioglitazone, or sitagliptin. Diabetologia. 2011, 54 (1): S314-Abstract 779
65.
go back to reference Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L: DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011, 96: 1301-1310. 10.1210/jc.2010-2081.PubMedCrossRef Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L: DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011, 96: 1301-1310. 10.1210/jc.2010-2081.PubMedCrossRef
66.
go back to reference Buse JB, Nauck MA, Forst T, Sheu WHH, Hoogwerf BJ, Shenouda SK, Heilmann CR, Boardman MK, Fineman M, Porter L, Schernthaner G: Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomised, open-label study. Diabetologia. 2011, 54 (1): S38-Abstract 75 Buse JB, Nauck MA, Forst T, Sheu WHH, Hoogwerf BJ, Shenouda SK, Heilmann CR, Boardman MK, Fineman M, Porter L, Schernthaner G: Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomised, open-label study. Diabetologia. 2011, 54 (1): S38-Abstract 75
67.
go back to reference Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE, EFC6018 GetGoal-Mono Study Investigators: Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-mono). Diabetes Care. 2012, 35: 1225-1231. 10.2337/dc11-1935.PubMedCentralPubMedCrossRef Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE, EFC6018 GetGoal-Mono Study Investigators: Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-mono). Diabetes Care. 2012, 35: 1225-1231. 10.2337/dc11-1935.PubMedCentralPubMedCrossRef
68.
go back to reference Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Hanefeld M: Efficacy and safety of lixisenatide once-daily versus placebo in patients with type 2 diabetes mellitus insufficiently controlled on metformin (GetGoal-F1). Diabetologia. 2011, 54 (1): S316-Abstract 784-P Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Hanefeld M: Efficacy and safety of lixisenatide once-daily versus placebo in patients with type 2 diabetes mellitus insufficiently controlled on metformin (GetGoal-F1). Diabetologia. 2011, 54 (1): S316-Abstract 784-P
69.
go back to reference Ahren B, Leguizamo Dimas A, Miossec P, Saubadu S, Aronson R, IDF: DF 2011 21th world congress abstract book. 2011, Dubai: IDF, 193-Oral 0591 Ahren B, Leguizamo Dimas A, Miossec P, Saubadu S, Aronson R, IDF: DF 2011 21th world congress abstract book. 2011, Dubai: IDF, 193-Oral 0591
70.
go back to reference Rosenstock J, Raccah D, Koranyi L, Maffei L, Boka G, Miossec P, Gerich JE: Efficacy and safety of lixisenatide once-daily vs exenatide twice-daily in type 2 DM inadequately controlled on metformin (GetGoal-X). Diabetes. 2011, 60 (1A): LB10-33-LB Rosenstock J, Raccah D, Koranyi L, Maffei L, Boka G, Miossec P, Gerich JE: Efficacy and safety of lixisenatide once-daily vs exenatide twice-daily in type 2 DM inadequately controlled on metformin (GetGoal-X). Diabetes. 2011, 60 (1A): LB10-33-LB
71.
go back to reference Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Aronson R: Efficacy and safety of lixisenatide once daily versus placebo in patients with type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes. 2012, 55 (1): 1010-P. Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Aronson R: Efficacy and safety of lixisenatide once daily versus placebo in patients with type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes. 2012, 55 (1): 1010-P.
72.
go back to reference Ratner RE, Hanefeld M, Shamanna P, Min K, Boka G, Miossec P, Muehlen-Bartmer I, Rosenstock J: Efficacy and safety of lixisenatide once-daily versus placebo in patients with type 2 diabetes mellitus insufficiently controlled on sulfonylurea ± metformin (GetGoal-S). Diabetologia. 2011, 54 (1): S317-Abstract 785-P Ratner RE, Hanefeld M, Shamanna P, Min K, Boka G, Miossec P, Muehlen-Bartmer I, Rosenstock J: Efficacy and safety of lixisenatide once-daily versus placebo in patients with type 2 diabetes mellitus insufficiently controlled on sulfonylurea ± metformin (GetGoal-S). Diabetologia. 2011, 54 (1): S317-Abstract 785-P
73.
go back to reference Rosenstock J, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Ping L, Riddle MC: Efficacy and safety of once-daily lixisenatide added on to titrated glargine plus oral agents in type 2 diabetes: GetGoal-Duo 1 study. Diabetes. 2012, 61 (1): 62-OR. Rosenstock J, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Ping L, Riddle MC: Efficacy and safety of once-daily lixisenatide added on to titrated glargine plus oral agents in type 2 diabetes: GetGoal-Duo 1 study. Diabetes. 2012, 61 (1): 62-OR.
74.
go back to reference Riddle MC, Home P, Marre M, Niemoeller E, Ping L, Rosenstock J: Efficacy and safety of once-daily lixisenatide in type 2 diabetes insufficiently controlled with basal insulin ± metformin: GetGoal-L study. Diabetes. 2012, 61 (1): 983-P. Riddle MC, Home P, Marre M, Niemoeller E, Ping L, Rosenstock J: Efficacy and safety of once-daily lixisenatide in type 2 diabetes insufficiently controlled with basal insulin ± metformin: GetGoal-L study. Diabetes. 2012, 61 (1): 983-P.
75.
go back to reference Seino Y, Min KW, Niemoeller E, Takami A, EFC10887 GETGOAL-L Asia Study Investigators: Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). Diab Obes Metab. 2012, 14: 910-917. 10.1111/j.1463-1326.2012.01618.x.CrossRef Seino Y, Min KW, Niemoeller E, Takami A, EFC10887 GETGOAL-L Asia Study Investigators: Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). Diab Obes Metab. 2012, 14: 910-917. 10.1111/j.1463-1326.2012.01618.x.CrossRef
76.
go back to reference Marre M, Shaw J, Brändle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S, LEAD-1 SU study group: Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med. 2009, 26: 268-278. 10.1111/j.1464-5491.2009.02666.x.PubMedCentralPubMedCrossRef Marre M, Shaw J, Brändle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S, LEAD-1 SU study group: Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med. 2009, 26: 268-278. 10.1111/j.1464-5491.2009.02666.x.PubMedCentralPubMedCrossRef
77.
go back to reference Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, Düring M, MAtthews DR, LEAD-2 Study Group: Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009, 32: 84-90. 10.2337/dc08-1355.PubMedCentralPubMedCrossRef Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, Düring M, MAtthews DR, LEAD-2 Study Group: Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009, 32: 84-90. 10.2337/dc08-1355.PubMedCentralPubMedCrossRef
78.
go back to reference Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B, LEAD-3 (Mono) Study Group: Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009, 373 (9662): 473-481. 10.1016/S0140-6736(08)61246-5.PubMedCrossRef Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B, LEAD-3 (Mono) Study Group: Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009, 373 (9662): 473-481. 10.1016/S0140-6736(08)61246-5.PubMedCrossRef
79.
go back to reference Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L, LEAD-4 Study Investigators: Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met + TZD). Diabetes Care. 2009, 32: 1224-1230. 10.2337/dc08-2124.PubMedCentralPubMedCrossRef Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L, LEAD-4 Study Investigators: Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met + TZD). Diabetes Care. 2009, 32: 1224-1230. 10.2337/dc08-2124.PubMedCentralPubMedCrossRef
80.
go back to reference Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Simó R, Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met + SU Study Group: Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met + SU): a randomised controlled trial. Diabetologia. 2009, 52: 2046-2055. 10.1007/s00125-009-1472-y.PubMedCentralPubMedCrossRef Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Simó R, Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met + SU Study Group: Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met + SU): a randomised controlled trial. Diabetologia. 2009, 52: 2046-2055. 10.1007/s00125-009-1472-y.PubMedCentralPubMedCrossRef
81.
go back to reference Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L, LEAD-6 Study Group: Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009, 374 (9683): 39-47. 10.1016/S0140-6736(09)60659-0.PubMedCrossRef Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L, LEAD-6 Study Group: Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009, 374 (9683): 39-47. 10.1016/S0140-6736(09)60659-0.PubMedCrossRef
82.
go back to reference Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Søndergaard RE, Davies M, 1860-LIRA-DPP-4 Study Group: Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010, 375 (9724): 1447-1456. 10.1016/S0140-6736(10)60307-8.PubMedCrossRef Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Søndergaard RE, Davies M, 1860-LIRA-DPP-4 Study Group: Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010, 375 (9724): 1447-1456. 10.1016/S0140-6736(10)60307-8.PubMedCrossRef
83.
go back to reference Pratley R, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Garber A, Thomsen AB, Hartvig H, Davies M, 1860-LIRA-DPP-4 Study Group: One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract. 2011, 65: 397-407. 10.1111/j.1742-1241.2011.02656.x.PubMedCentralPubMedCrossRef Pratley R, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Garber A, Thomsen AB, Hartvig H, Davies M, 1860-LIRA-DPP-4 Study Group: One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract. 2011, 65: 397-407. 10.1111/j.1742-1241.2011.02656.x.PubMedCentralPubMedCrossRef
84.
go back to reference Niswender K, Pi-Sunyer X, Buse J, Jensen KH, Toft AD, Russell-Jones D, Zinman B: Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab. 2013, 15: 42-54. 10.1111/j.1463-1326.2012.01673.x.PubMedCrossRef Niswender K, Pi-Sunyer X, Buse J, Jensen KH, Toft AD, Russell-Jones D, Zinman B: Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab. 2013, 15: 42-54. 10.1111/j.1463-1326.2012.01673.x.PubMedCrossRef
85.
go back to reference Padwal R, Straus SE, McAlister FA: Evidence based management of hypertension. Cardiovascular risk factors and their effects on the decision to treat hypertension: evidence based review. BMJ. 2001, 322 (7292): 977-980. 10.1136/bmj.322.7292.977.PubMedCentralPubMedCrossRef Padwal R, Straus SE, McAlister FA: Evidence based management of hypertension. Cardiovascular risk factors and their effects on the decision to treat hypertension: evidence based review. BMJ. 2001, 322 (7292): 977-980. 10.1136/bmj.322.7292.977.PubMedCentralPubMedCrossRef
86.
go back to reference Ferrannini E, Cushman WC: Diabetes and hypertension: the bad companions. Lancet. 2012, 380 (9841): 601-610. 10.1016/S0140-6736(12)60987-8.PubMedCrossRef Ferrannini E, Cushman WC: Diabetes and hypertension: the bad companions. Lancet. 2012, 380 (9841): 601-610. 10.1016/S0140-6736(12)60987-8.PubMedCrossRef
87.
go back to reference Ogawa S, Ishiki M, Nako K, Okamura M, Senda M, Mori T, Ito S: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes. Tohoku J Exp Med. 2011, 223: 133-135. 10.1620/tjem.223.133.PubMedCrossRef Ogawa S, Ishiki M, Nako K, Okamura M, Senda M, Mori T, Ito S: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes. Tohoku J Exp Med. 2011, 223: 133-135. 10.1620/tjem.223.133.PubMedCrossRef
88.
go back to reference Kubota A, Maeda H, Kanamori A, Matoba K, Jin Y, Minagawa F, Obana M, Iemitsu K, Ito S, Amemiya H, Kaneshiro M, Takai M, Kaneshige H, Hoshino K, Ishikawa M, Minami N, Takuma T, Sasai N, Aoyagi S, Kawata T, Mokubo A, Takeda H, Honda S, Machimura H, Motomiya T, Waseda M, Naka Y, Tanaka Y, Terauchi Y, Matsuba I: Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients. J Clin Med Res. 2012, 4: 309-313.PubMedCentralPubMed Kubota A, Maeda H, Kanamori A, Matoba K, Jin Y, Minagawa F, Obana M, Iemitsu K, Ito S, Amemiya H, Kaneshiro M, Takai M, Kaneshige H, Hoshino K, Ishikawa M, Minami N, Takuma T, Sasai N, Aoyagi S, Kawata T, Mokubo A, Takeda H, Honda S, Machimura H, Motomiya T, Waseda M, Naka Y, Tanaka Y, Terauchi Y, Matsuba I: Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients. J Clin Med Res. 2012, 4: 309-313.PubMedCentralPubMed
89.
go back to reference Koren S, Shemesh-Bar L, Tirosh A, Peleg RK, Berman S, Hamad RA, Vinker S, Golik A, Efrati S: The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients. Diabetes Technol Ther. 2012, 14: 561-567. 10.1089/dia.2011.0296.PubMedCrossRef Koren S, Shemesh-Bar L, Tirosh A, Peleg RK, Berman S, Hamad RA, Vinker S, Golik A, Efrati S: The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients. Diabetes Technol Ther. 2012, 14: 561-567. 10.1089/dia.2011.0296.PubMedCrossRef
90.
go back to reference von Eynatten M, Gong Y, Emser A, Woerle HJ: Efficacy and safety of linagliptin in type 2 diabetes subjects at high risk for renal and cardiovascular disease: a pooled analysis of six phase III clinical trials. Cardiovasc Diabetol. 2013, 12: 60-10.1186/1475-2840-12-60.PubMedCentralPubMedCrossRef von Eynatten M, Gong Y, Emser A, Woerle HJ: Efficacy and safety of linagliptin in type 2 diabetes subjects at high risk for renal and cardiovascular disease: a pooled analysis of six phase III clinical trials. Cardiovasc Diabetol. 2013, 12: 60-10.1186/1475-2840-12-60.PubMedCentralPubMedCrossRef
91.
go back to reference Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008, 24: 275-286.PubMedCrossRef Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008, 24: 275-286.PubMedCrossRef
92.
go back to reference Gallwitz B, Vaag A, Falahati A, Madsbad S: Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time. Int J Clin Pract. 2010, 64: 267-276.PubMedCrossRef Gallwitz B, Vaag A, Falahati A, Madsbad S: Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time. Int J Clin Pract. 2010, 64: 267-276.PubMedCrossRef
93.
go back to reference Fonseca V, Falahati A, Zychma M, Madsbad S, Plutzky J: Liraglutide, a once-daily human GLP-1 analogue, reduces systolic blood pressure within 2 weeks in patients with type 2 diabetes. 2009, Montreal: IDF 2009 20th World Congress Abstract Book. IDF, 310-Poster D-0908 Fonseca V, Falahati A, Zychma M, Madsbad S, Plutzky J: Liraglutide, a once-daily human GLP-1 analogue, reduces systolic blood pressure within 2 weeks in patients with type 2 diabetes. 2009, Montreal: IDF 2009 20th World Congress Abstract Book. IDF, 310-Poster D-0908
94.
go back to reference Fonseca V, Plutzky J, Montanya E, Colagiuri S, Hansen CT, Falahati A, DeVries JH: Liraglutide, a once-daily human GLP-1 analog, lowers systolic blood pressure (SBP) independently of concomitant antihypertensive treatment. Diabetes. 2010, 59 (1): A78-Abstract 296-OR Fonseca V, Plutzky J, Montanya E, Colagiuri S, Hansen CT, Falahati A, DeVries JH: Liraglutide, a once-daily human GLP-1 analog, lowers systolic blood pressure (SBP) independently of concomitant antihypertensive treatment. Diabetes. 2010, 59 (1): A78-Abstract 296-OR
95.
go back to reference Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, Simpson JA, Drucker DJ: GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med. 2013, 19 (5): 567-575. 10.1038/nm.3128.PubMedCrossRef Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, Simpson JA, Drucker DJ: GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med. 2013, 19 (5): 567-575. 10.1038/nm.3128.PubMedCrossRef
96.
go back to reference Nyström T, Gonon AT, Sjöholm A, Pernow J: Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul Pept. 2005, 125 (1–3): 173-177.PubMedCrossRef Nyström T, Gonon AT, Sjöholm A, Pernow J: Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul Pept. 2005, 125 (1–3): 173-177.PubMedCrossRef
98.
99.
go back to reference Amori RE, Lau J, Pittas AG: Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007, 298: 194-206. 10.1001/jama.298.2.194.PubMedCrossRef Amori RE, Lau J, Pittas AG: Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007, 298: 194-206. 10.1001/jama.298.2.194.PubMedCrossRef
100.
go back to reference Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P: Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes. Diabetes Obes Metab. 2011, 13: 366-373. 10.1111/j.1463-1326.2011.01362.x.PubMedCrossRef Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P: Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes. Diabetes Obes Metab. 2011, 13: 366-373. 10.1111/j.1463-1326.2011.01362.x.PubMedCrossRef
101.
go back to reference Matikainen N, Mänttäri S, Schweizer A, Ulvestad A, Mills D, Dunning BE, Foley JE, Taskinen MR: Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes. Diabetologia. 2006, 49: 2049-2057. 10.1007/s00125-006-0340-2.PubMedCrossRef Matikainen N, Mänttäri S, Schweizer A, Ulvestad A, Mills D, Dunning BE, Foley JE, Taskinen MR: Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes. Diabetologia. 2006, 49: 2049-2057. 10.1007/s00125-006-0340-2.PubMedCrossRef
102.
go back to reference Eliasson B, Möller-Goede D, Eeg-Olofsson K, Wilson C, Cederholm J, Fleck P, Diamant M, Taskinen MR, Smith U: Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study. Diabetologia. 2012, 55 (4): 915-925. 10.1007/s00125-011-2447-3.PubMedCrossRef Eliasson B, Möller-Goede D, Eeg-Olofsson K, Wilson C, Cederholm J, Fleck P, Diamant M, Taskinen MR, Smith U: Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study. Diabetologia. 2012, 55 (4): 915-925. 10.1007/s00125-011-2447-3.PubMedCrossRef
103.
go back to reference Ansar S, Koska J, Reaven PD: Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins. Cardiovasc Diabetol. 2011, 10: 61-10.1186/1475-2840-10-61.PubMedCentralPubMedCrossRef Ansar S, Koska J, Reaven PD: Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins. Cardiovasc Diabetol. 2011, 10: 61-10.1186/1475-2840-10-61.PubMedCentralPubMedCrossRef
104.
go back to reference Plutzky J, Garber A, Toft AD, Toft AD, Poulter NR: Meta-analysis demonstrates that liraglutide, a once-daily human GLP-1 analogue, significantly reduces lipids and other markers of cardiovascular risk in type 2 diabetes. Diabetologia. 2009, 52 (Suppl. 1): S299. Plutzky J, Garber A, Toft AD, Toft AD, Poulter NR: Meta-analysis demonstrates that liraglutide, a once-daily human GLP-1 analogue, significantly reduces lipids and other markers of cardiovascular risk in type 2 diabetes. Diabetologia. 2009, 52 (Suppl. 1): S299.
105.
go back to reference Plutzky J, Poulter NR, Falahati A, Toft A, Davidson MH: Plasminogen activator inhibitor-1 is reduced by the once-daily human glucagon-like peptide-1 analog liraglutide when used in the treatment of type 2 diabetes. Circulation. 2009, 120 (Suppl. 2): S397. Plutzky J, Poulter NR, Falahati A, Toft A, Davidson MH: Plasminogen activator inhibitor-1 is reduced by the once-daily human glucagon-like peptide-1 analog liraglutide when used in the treatment of type 2 diabetes. Circulation. 2009, 120 (Suppl. 2): S397.
106.
go back to reference Varanasi A, Patel P, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P: Clinical Use of liraglutide in type 2 diabetes, and its effects on cardiovascular risk factors. Endocr Pract. 2012, 18: 140-145. 10.4158/EP11169.OR.PubMedCrossRef Varanasi A, Patel P, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P: Clinical Use of liraglutide in type 2 diabetes, and its effects on cardiovascular risk factors. Endocr Pract. 2012, 18: 140-145. 10.4158/EP11169.OR.PubMedCrossRef
107.
go back to reference Varanasi A, Chaudhuri A, Dhindsa S, Arora A, Lohano T, Vora MR, Dandona P: Durability of effects of exenatide treatment on glycemic control, body weight, systolic blood pressure, C-reactive protein, and triglyceride concentrations. Endocr Pract. 2011, 17: 192-200. 10.4158/EP10199.OR.PubMedCrossRef Varanasi A, Chaudhuri A, Dhindsa S, Arora A, Lohano T, Vora MR, Dandona P: Durability of effects of exenatide treatment on glycemic control, body weight, systolic blood pressure, C-reactive protein, and triglyceride concentrations. Endocr Pract. 2011, 17: 192-200. 10.4158/EP10199.OR.PubMedCrossRef
108.
go back to reference Forst T, Michelson G, Ratter F, Weber MM, Anders S, Mitry M, Wilhelm B, Pfützner A: Addition of liraglutide in patients with type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet Med. 2012, 29: 1115-1118.PubMedCrossRef Forst T, Michelson G, Ratter F, Weber MM, Anders S, Mitry M, Wilhelm B, Pfützner A: Addition of liraglutide in patients with type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet Med. 2012, 29: 1115-1118.PubMedCrossRef
109.
go back to reference Jensen MT, Marott JL, Allin KH, Nordestgaard BG, Jensen GB: Resting heart rate is associated with cardiovascular and all-cause mortality after adjusting for inflammatory markers: the Copenhagen city heart study. Eur J Prev Cardiol. 2012, 19: 102-108. 10.1177/1741826710394274.PubMedCrossRef Jensen MT, Marott JL, Allin KH, Nordestgaard BG, Jensen GB: Resting heart rate is associated with cardiovascular and all-cause mortality after adjusting for inflammatory markers: the Copenhagen city heart study. Eur J Prev Cardiol. 2012, 19: 102-108. 10.1177/1741826710394274.PubMedCrossRef
110.
go back to reference van Noord C, Eijgelsheim M, Stricker BH: Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol. 2010, 70: 16-23. 10.1111/j.1365-2125.2010.03660.x.PubMedCentralPubMedCrossRef van Noord C, Eijgelsheim M, Stricker BH: Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol. 2010, 70: 16-23. 10.1111/j.1365-2125.2010.03660.x.PubMedCentralPubMedCrossRef
112.
go back to reference Ring A, Port A, Graefe-Mody EU, Revollo I, Iovino M, Dugi KA: The DPP-4 inhibitor linagliptin does not prolong the QT interval at therapeutic and supratherapeutic doses. Br J Clin Pharmacol. 2011, 72: 39-50. 10.1111/j.1365-2125.2011.03931.x.PubMedCentralPubMedCrossRef Ring A, Port A, Graefe-Mody EU, Revollo I, Iovino M, Dugi KA: The DPP-4 inhibitor linagliptin does not prolong the QT interval at therapeutic and supratherapeutic doses. Br J Clin Pharmacol. 2011, 72: 39-50. 10.1111/j.1365-2125.2011.03931.x.PubMedCentralPubMedCrossRef
113.
go back to reference Nathanson D, Ullman B, Löfström U, Hedman A, Frick M, Sjöholm A, Nyström T: Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: a double-blind, randomised controlled clinical trial of efficacy and safety. Diabetologia. 2012, 55 (4): 926-935. 10.1007/s00125-011-2440-x.PubMedCrossRef Nathanson D, Ullman B, Löfström U, Hedman A, Frick M, Sjöholm A, Nyström T: Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: a double-blind, randomised controlled clinical trial of efficacy and safety. Diabetologia. 2012, 55 (4): 926-935. 10.1007/s00125-011-2440-x.PubMedCrossRef
114.
go back to reference Gill A, Hoogwerf BJ, Burger J, Bruce S, Macconell L, Yan P, Braun D, Giaconia J, Malone J: Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study. Cardiovasc Diabetol. 2010, 9: 6-10.1186/1475-2840-9-6.PubMedCentralPubMedCrossRef Gill A, Hoogwerf BJ, Burger J, Bruce S, Macconell L, Yan P, Braun D, Giaconia J, Malone J: Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study. Cardiovasc Diabetol. 2010, 9: 6-10.1186/1475-2840-9-6.PubMedCentralPubMedCrossRef
115.
go back to reference Bloomfield DM, Krishna R, Hreniuk D, Hickey L, Ghosh K, Bergman AJ, Miller J, Gutierrez MJ, Stoltz R, Gottesdiener KM, Herman GA, Wagner JA: A thorough QTc study to assess the effect of sitagliptin, a DPP4 inhibitor, on ventricular repolarization in healthy subjects. J Clin Pharmacol. 2009, 49: 937-946. 10.1177/0091270009337511.PubMedCrossRef Bloomfield DM, Krishna R, Hreniuk D, Hickey L, Ghosh K, Bergman AJ, Miller J, Gutierrez MJ, Stoltz R, Gottesdiener KM, Herman GA, Wagner JA: A thorough QTc study to assess the effect of sitagliptin, a DPP4 inhibitor, on ventricular repolarization in healthy subjects. J Clin Pharmacol. 2009, 49: 937-946. 10.1177/0091270009337511.PubMedCrossRef
116.
go back to reference He YL, Zhang Y, Serra D, Wang Y, Ligueros-Saylan M, Dole WP: Thorough QT study of the effects of vildagliptin, a dipeptidyl peptidase IV inhibitor, on cardiac repolarization and conduction in healthy volunteers. Curr Med Res Opin. 2011, 27: 1453-1463. 10.1185/03007995.2011.585395.PubMedCrossRef He YL, Zhang Y, Serra D, Wang Y, Ligueros-Saylan M, Dole WP: Thorough QT study of the effects of vildagliptin, a dipeptidyl peptidase IV inhibitor, on cardiac repolarization and conduction in healthy volunteers. Curr Med Res Opin. 2011, 27: 1453-1463. 10.1185/03007995.2011.585395.PubMedCrossRef
117.
go back to reference Chatterjee DJ, Khutoryansky N, Zdravkovic M, Sprenger CR, Litwin JS: Absence of QTc prolongation in a thorough QT study with subcutaneous liraglutide, a once-daily human GLP-1 analog for treatment of type 2 diabetes. J Clin Pharmacol. 2009, 49: 1353-1362. 10.1177/0091270009339189.PubMedCrossRef Chatterjee DJ, Khutoryansky N, Zdravkovic M, Sprenger CR, Litwin JS: Absence of QTc prolongation in a thorough QT study with subcutaneous liraglutide, a once-daily human GLP-1 analog for treatment of type 2 diabetes. J Clin Pharmacol. 2009, 49: 1353-1362. 10.1177/0091270009339189.PubMedCrossRef
118.
go back to reference Linnebjerg H, Seger M, Kothare PA, Hunt T, Wolka AM, Mitchell MI: A thorough QT study to evaluate the effects of single dose exenatide 10 μg on cardiac repolarization in healthy subjects. Int J Clin Pharmacol Ther. 2011, 49: 594-604. 10.5414/CP201462.PubMedCrossRef Linnebjerg H, Seger M, Kothare PA, Hunt T, Wolka AM, Mitchell MI: A thorough QT study to evaluate the effects of single dose exenatide 10 μg on cardiac repolarization in healthy subjects. Int J Clin Pharmacol Ther. 2011, 49: 594-604. 10.5414/CP201462.PubMedCrossRef
119.
go back to reference Darpö B, Sager P, Macconell L, Cirincione B, Mitchell M, Han J, Huang W, Malloy J, Schulteis C, Shen L, Porter L: Exenatide at therapeutic and supratherapeutic concentrations does Not prolong the QTc interval in healthy subjects. Br J Clin Pharmacol. 2012, 10.1111/j.1365-2125.2012.04416.x. Darpö B, Sager P, Macconell L, Cirincione B, Mitchell M, Han J, Huang W, Malloy J, Schulteis C, Shen L, Porter L: Exenatide at therapeutic and supratherapeutic concentrations does Not prolong the QTc interval in healthy subjects. Br J Clin Pharmacol. 2012, 10.1111/j.1365-2125.2012.04416.x.
120.
go back to reference Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, Baggio LL, Henkelman RM, Husain M, Drucker DJ: GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009, 58: 975-983. 10.2337/db08-1193.PubMedCentralPubMedCrossRef Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, Baggio LL, Henkelman RM, Husain M, Drucker DJ: GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009, 58: 975-983. 10.2337/db08-1193.PubMedCentralPubMedCrossRef
121.
go back to reference Sonne DP, Engstrøm T, Treiman M: Protective effects of GLP-1 analogues exendin-4 and GLP-1(9–36) amide against ischemia-reperfusion injury in rat heart. Regul Pept. 2008, 146: 243-249. 10.1016/j.regpep.2007.10.001.PubMedCrossRef Sonne DP, Engstrøm T, Treiman M: Protective effects of GLP-1 analogues exendin-4 and GLP-1(9–36) amide against ischemia-reperfusion injury in rat heart. Regul Pept. 2008, 146: 243-249. 10.1016/j.regpep.2007.10.001.PubMedCrossRef
122.
go back to reference Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE: Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009, 53: 501-510. 10.1016/j.jacc.2008.10.033.PubMedCrossRef Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE: Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009, 53: 501-510. 10.1016/j.jacc.2008.10.033.PubMedCrossRef
123.
go back to reference Lønborg J, Vejlstrup N, Kelbæk H, Bøtker HE, Kim WY, Mathiasen AB, Jørgensen E, Helqvist S, Saunamäki K, Clemmensen P, Holmvang L, Thuesen L, Krusell LR, Jensen JS, Køber L, Treiman M, Holst JJ, Engstrøm T: Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012, 33: 1491-1499. 10.1093/eurheartj/ehr309.PubMedCrossRef Lønborg J, Vejlstrup N, Kelbæk H, Bøtker HE, Kim WY, Mathiasen AB, Jørgensen E, Helqvist S, Saunamäki K, Clemmensen P, Holmvang L, Thuesen L, Krusell LR, Jensen JS, Køber L, Treiman M, Holst JJ, Engstrøm T: Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012, 33: 1491-1499. 10.1093/eurheartj/ehr309.PubMedCrossRef
124.
go back to reference Lønborg J, Kelbæk H, Vejlstrup N, Bøtker HE, Kim WY, Holmvang L, Jørgensen E, Helqvist S, Saunamäki K, Terkelsen CJ, Schoos MM, Køber L, Clemmensen P, Treiman M, Engstrøm T: Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ Cardiovasc Interv. 2012, 5: 288-295. 10.1161/CIRCINTERVENTIONS.112.968388.PubMedCrossRef Lønborg J, Kelbæk H, Vejlstrup N, Bøtker HE, Kim WY, Holmvang L, Jørgensen E, Helqvist S, Saunamäki K, Terkelsen CJ, Schoos MM, Køber L, Clemmensen P, Treiman M, Engstrøm T: Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ Cardiovasc Interv. 2012, 5: 288-295. 10.1161/CIRCINTERVENTIONS.112.968388.PubMedCrossRef
125.
go back to reference Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ: Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord. 2010, 10: 7-10.1186/1472-6823-10-7.PubMedCentralPubMedCrossRef Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ: Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord. 2010, 10: 7-10.1186/1472-6823-10-7.PubMedCentralPubMedCrossRef
126.
go back to reference White WB, Pratley R, Fleck P, Munsaka M, Hisada M, Wilson C, Menon V: Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus. Diabetes Obes Metab. 2013, 15 (7): 668-673. 10.1111/dom.12093.PubMedCrossRef White WB, Pratley R, Fleck P, Munsaka M, Hisada M, Wilson C, Menon V: Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus. Diabetes Obes Metab. 2013, 15 (7): 668-673. 10.1111/dom.12093.PubMedCrossRef
127.
go back to reference Wu D, Li L, Liu C: Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2013, 10.1111/dom.12174. Wu D, Li L, Liu C: Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2013, 10.1111/dom.12174.
128.
go back to reference Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, Dugi KA, Woerle HJ: 2-Year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012, 380 (9840): 475-483. 10.1016/S0140-6736(12)60691-6.PubMedCrossRef Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, Dugi KA, Woerle HJ: 2-Year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012, 380 (9840): 475-483. 10.1016/S0140-6736(12)60691-6.PubMedCrossRef
129.
go back to reference Monami M, Cremasco F, Lamanna C, Colombi C, Desideri CM, Iacomelli I, Marchionni N, Mannucci E: Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Exp Diabetes Res. 2011, 2011: 215764-10.1155/2011/215764.PubMedCentralPubMed Monami M, Cremasco F, Lamanna C, Colombi C, Desideri CM, Iacomelli I, Marchionni N, Mannucci E: Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Exp Diabetes Res. 2011, 2011: 215764-10.1155/2011/215764.PubMedCentralPubMed
130.
go back to reference Marso SP, Lindsey JB, Stolker JM, House JA, Martinez Ravn G, Kennedy KF, Jensen TM, Buse JB: Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies. Diab Vasc Dis Res. 2011, 8: 237-240. 10.1177/1479164111408937.PubMedCrossRef Marso SP, Lindsey JB, Stolker JM, House JA, Martinez Ravn G, Kennedy KF, Jensen TM, Buse JB: Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies. Diab Vasc Dis Res. 2011, 8: 237-240. 10.1177/1479164111408937.PubMedCrossRef
131.
go back to reference Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MA: Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011, 34: 90-95. 10.2337/dc10-1393.PubMedCentralPubMedCrossRef Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MA: Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011, 34: 90-95. 10.2337/dc10-1393.PubMedCentralPubMedCrossRef
132.
go back to reference Ratner R, Han J, Nicewarner D, Yushmanova I, Hoogwerf BJ, Shen L: Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 22-10.1186/1475-2840-10-22.PubMedCentralPubMedCrossRef Ratner R, Han J, Nicewarner D, Yushmanova I, Hoogwerf BJ, Shen L: Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol. 2011, 10: 22-10.1186/1475-2840-10-22.PubMedCentralPubMedCrossRef
Metadata
Title
The cardiovascular safety of incretin-based therapies: a review of the evidence
Author
John R Petrie
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2013
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-12-130

Other articles of this Issue 1/2013

Cardiovascular Diabetology 1/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.