The non-glycemic effects of incretin therapies on cardiovascular outcomes, cognitive function and bone health

References

• Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev 2008;60(4):470-512
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Powell AM, Kaidanovich-Beilin O, et al. The neuroprotective effects of GLP-1: possible treatments for cognitive deficits in individuals with mood disorders. Behav Brain Res 2013;237:164-71
   PubMed Web of Science ®Google Scholar
• Advani A, Bugyei-Twum A, Connelly KA. Cardiovascular Effects of Incretins in Diabetes. Can J Diabetes 2013;37(5):309-14
   PubMedGoogle Scholar
• Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132(6):2131-57
   PubMed Web of Science ®Google Scholar
• Phillips LK, Prins JB. Update on incretin hormones. Ann N Y Acad Sci 2012;1243:E55-74
   Google Scholar
• Ahrén B, Landin-Olsson M, Jansson PA, et al. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004;89(5):2078-84
   PubMed Web of Science ®Google Scholar
• Hocher B, Reichetzeder C, Alter ML. Renal and cardiac effects of DPP4 inhibitors–from preclinical development to clinical research. Kidney Blood Press Res 2012;36(1):65-84
   PubMed Web of Science ®Google Scholar
• Ban K, Noyan-Ashraf MH, Hoefer J, et al. 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(18):2340-50
   PubMed Web of Science ®Google Scholar
• Gros R, You X, Baggio LL, et al. Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 2003;144(6):2242-52
   PubMed Web of Science ®Google Scholar
• Nikolaidis LA, Elahi D, Shen YT, Shannon RP. Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 2005;289(6):H2401-8
   Google Scholar
• Nikolaidis LA, Elahi D, Hentosz T, et al. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 2004;110(8):955-61
   PubMed Web of Science ®Google Scholar
• Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33(2):187-215
   PubMed Web of Science ®Google Scholar
• Timmers L, Henriques JP, de Kleijn DP, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 2009;53(6):501-10
   PubMed Web of Science ®Google Scholar
• Kristensen J, Mortensen UM, Schmidt M, et al. Lack of cardioprotection from subcutaneously and preischemic administered liraglutide in a closed chest porcine ischemia reperfusion model. BMC Cardiovasc Disord 2009;9:31
   PubMed Web of Science ®Google Scholar
• Sauvé M, Ban K, Momen MA, et al. Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice. Diabetes 2010;59(4):1063-73
   PubMed Web of Science ®Google Scholar
• Connelly KA, Zhang Y, Advani A, et al. DPP-4 Inhibition Improves Cardiac Function Following Experimental Myocardial Infarction: potential Non-GLP-1 Mediated Effects. Can J Cardiology 2012;28(5):S397-S98
   Google Scholar
• Connelly KA, Zhang Y, Advani A, et al. DPP-4 inhibition attenuates cardiac dysfunction and adverse remodeling following myocardial infarction in rats with experimental diabetes. Cardiovasc Ther 2013;31(5):259-67
   PubMed Web of Science ®Google Scholar
• Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991;325(21):1468-75
   PubMed Web of Science ®Google Scholar
• Pratley R, Nauck M, Bailey T, et al. 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(4):397-407
   PubMed Web of Science ®Google Scholar
• Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open 2013;3(1):pii: e001986
   Web of Science ®Google Scholar
• Pyke C, Heller RS, Kirk RK, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 2014;155(4):1280-90
   PubMed Web of Science ®Google Scholar
• Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res 2014;114(11):1788-803
   PubMed Web of Science ®Google Scholar
• Fox K, Ford I, Steg PG, et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008;372(9641):817-21
   PubMed Web of Science ®Google Scholar
• Mundil D, Cameron-Vendrig A, Husain M. GLP-1 receptor agonists: a clinical perspective on cardiovascular effects. Diab Vasc Dis Res 2012;9(2):95-108
   PubMed Web of Science ®Google Scholar
• Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364(9438):937-52
   PubMed Web of Science ®Google Scholar
• Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA 1996;275(20):1571-6
   PubMed Web of Science ®Google Scholar
• Halbirk M, Norrelund H, Moller N, et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol 2010;298(3):H1096-102
   Google Scholar
• Barragan JM, Eng J, Rodriguez R, Blazquez E. Neural contribution to the effect of glucagon-like peptide-1-(7-36) amide on arterial blood pressure in rats. Am J Physiol 1999;277(5 Pt 1):E784-91
   PubMed Web of Science ®Google Scholar
• Yamamoto H, Lee CE, Marcus JN, et al. Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin Invest 2002;110(1):43-52
   PubMedGoogle Scholar
• Yang W, Chen L, Ji Q, et al. Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*). Diabetes Obes Metab 2011;13(1):81-8
   PubMed Web of Science ®Google Scholar
• 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(2):267-76
   PubMedGoogle Scholar
• Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog. liraglutide. Int J Obes (Lond) 2012;36(6):843-54
   PubMed Web of Science ®Google Scholar
• Nauck M, Frid A, Hermansen K, et al. 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(1):84-90
   PubMed Web of Science ®Google Scholar
• Pratley RE, Nauck M, Bailey T, et al. 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):1447-56
   PubMed Web of Science ®Google Scholar
• Marre M, Shaw J, Brändle M, et al. 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(3):268-78
   PubMed Web of Science ®Google Scholar
• Gill A, Hoogwerf BJ, Burger J, et al. 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
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Cardiovascular effects of gliptins. Nat Rev Cardiol 2013;10(2):73-84
   PubMed Web of Science ®Google Scholar
• Kim M, Platt MJ, Shibasaki T, et al. GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med 2013;19(5):567-75
   PubMed Web of Science ®Google Scholar
• Lønborg J, Vejlstrup N, Kelbæk H, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J 2012;33(12):1491-9
   PubMed Web of Science ®Google Scholar
• Frederich R, Alexander JH, Fiedorek FT, et al. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 2010;122(3):16-27
   PubMed Web of Science ®Google Scholar
• Monami M, Ahrén B, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013;15(2):112-20
   PubMed Web of Science ®Google Scholar
• Marso SP, Lindsey JB, Stolker JM, et al. 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(3):237-40
   PubMed Web of Science ®Google Scholar
• Ratner R, Han J, Nicewarner D, et al. Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol 2011;10:22
   PubMed Web of Science ®Google Scholar
• Monami M, Cremasco F, Lamanna C, et al. Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Exp Diabetes Res 2011;2011:215764
   PubMedGoogle Scholar
• Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369(14):1317-26
   PubMed Web of Science ®Google Scholar
• White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369(14):1327-35
   PubMed Web of Science ®Google Scholar
• Scirica BM, Braunwald E, Raz I, et al. Heart Failure, Saxagliptin and Diabetes Mellitus: observations from the SAVOR - TIMI 53 Randomized Trial. Circulation 2014; [Epub ahead of print]
   Google Scholar
• Zannad F, Cannon C, Cushman W, et al. Alogliptin in patients with type 2 diabetes after acute coronary syndromes: heart failure outcomes and cardiovascular safety in heart failure patients. JACC 2014;63(12):A1117
   Google Scholar
• Weir DL, McAlister FA, Senthilselvan A, et al. Sitagliptin Use in Patients With Diabetes and Heart Failure: a Population-Based Retrospective Cohort Study. JACC Heart Fail 2014. [Epub ahead of print]
   Google Scholar
• Alvarez E, Martinez MD, Roncero I, et al. The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem. J Neurochem 2005;92(4):798-806
   PubMed Web of Science ®Google Scholar
• Göke R, Larsen PJ, Mikkelsen JD, Sheikh SP. Distribution of GLP-1 binding sites in the rat brain: evidence that exendin-4 is a ligand of brain GLP-1 binding sites. Eur J Neurosci 1995;7(11):2294-300
   PubMed Web of Science ®Google Scholar
• Navarro M, Rodriquez de Fonseca F, Alvarez E, et al. Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neurochem 1996;67(5):1982-91
   PubMed Web of Science ®Google Scholar
• Merchenthaler I, Lane M, Shughrue P. Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol 1999;403(2):261-80
   PubMed Web of Science ®Google Scholar
• Hunter K, and Hölscher C. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci 2012;13:33
   PubMed Web of Science ®Google Scholar
• Kastin AJ, Akerstrom V, Pan W. Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier. J Mol Neurosci 2002;18(1-2):7-14
   PubMed Web of Science ®Google Scholar
• Perry T, Lahiri DK, Sambamurti K, et al. Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron. J Neurosci Res 2003;72(5):603-12
   PubMed Web of Science ®Google Scholar
• Kimura R, Okouchi M, Fujioka H, et al. Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. Neuroscience 2009;162(4):1212-19
   PubMed Web of Science ®Google Scholar
• Biswas SC, Buteau J, Greene LA. Glucagon-like peptide-1 (GLP-1) diminishes neuronal degeneration and death caused by NGF deprivation by suppressing Bim induction. Neurochem Res 2008;33(9):1845-51
   PubMed Web of Science ®Google Scholar
• Li Y, Perry T, Kindy MS, et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci USA 2009;106(4):1285-90
   PubMed Web of Science ®Google Scholar
• Li Y, Duffy KB, Ottinger MA, et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease. J Alzheimers Dis 2010;19(4):1205-19
   PubMed Web of Science ®Google Scholar
• McClean PL, Parthsarathy V, Faivre E, Hölscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J Neurosci 2011;31(17):6587-94
   PubMed Web of Science ®Google Scholar
• Porter DW, Kerr BD, Flatt PR, et al. Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary-induced obesity and insulin resistance. Diabetes Obes Metab 2010;12(10):891-9
   PubMed Web of Science ®Google Scholar
• Gault VA, Porter WD, Flatt PR, Hölscher C. Actions of exendin-4 therapy on cognitive function and hippocampal synaptic plasticity in mice fed a high-fat diet. Int J Obes (Lond) 2010;34(8):1341-4
   PubMedGoogle Scholar
• McClean PL, Gault VA, Harriott P, Hölscher C. Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer’s disease. Eur J Pharmacol 2010;630(1-3):158-62
   PubMed Web of Science ®Google Scholar
• Abbas T, Faivre E, Hölscher C. Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: interaction between type 2 diabetes and Alzheimer’s disease. Behav Brain Res 2009;205(1):265-71
   PubMed Web of Science ®Google Scholar
• Treatment of antipsychotic-associated obesity with a glp-1 analogue (TAO). Available from: http://clinicaltrials.gov/show/NCT01794429
   Google Scholar
• Exenatide for the treatment of weight gain associated with olanzapine in obese adults. Available from: http://clinicaltrials.gov/show/NCT00845507
   Google Scholar
• Hölscher C. Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol 2014;221(1):T31-41
   PubMed Web of Science ®Google Scholar
• Lecka-Czernik B. Safety of anti-diabetic therapies on bone. Clin Rev Bone Miner Metab 2013;11(1):49-58
   PubMedGoogle Scholar
• Bollag RJ, Zhong Q, Phillips P, et al. Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors. Endocrinology 2000;141(3):1228-35
   PubMed Web of Science ®Google Scholar
• Tsukiyama K, Yamada Y, Yamada C, et al. Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Mol Endocrinol 2006;20(7):1644-51
   PubMedGoogle Scholar
• Zhong Q, Itokawa T, Sridhar S, et al. Effects of glucose-dependent insulinotropic peptide on osteoclast function. Am J Physiol Endocrinol Metab 2007;292(2):E543-8
   PubMed Web of Science ®Google Scholar
• Xie D, Zhong Q, Ding KH, et al. Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass. Bone 2007;40(5):1352-60
   PubMedGoogle Scholar
• Yamada C, Yamada Y, Tsukiyama K, et al. The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology 2008;149(2):574-9
   PubMed Web of Science ®Google Scholar
• Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA 1996;93(15):7911-16
   PubMed Web of Science ®Google Scholar
• Wallis K, Walters JR, Forbes A. Review article: glucagon-like peptide 2–current applications and future directions. Aliment Pharmacol Ther 2007;25(4):365-72
   PubMedGoogle Scholar
• Brubaker PL, Anini Y. Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol 2003;81(11):1005-12
   PubMed Web of Science ®Google Scholar
• Xiao Q, Boushey RP, Drucker DJ, Brubaker PL. Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans. Gastroenterology 1999;117(1):99-105
   PubMedGoogle Scholar
• Henriksen DB, Alexandersen P, Hartmann B, et al. Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women. Bone 2007;40(3):723-9
   PubMedGoogle Scholar
• Henriksen DB, Alexandersen P, Hartmann B, et al. Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone 2009;45(5):833-42
   PubMed Web of Science ®Google Scholar
• Montagnani A, Gonnelli S. Antidiabetic therapy effects on bone metabolism and fracture risk. Diabetes Obes Metab 2013;15(9):784-91
   PubMed Web of Science ®Google Scholar
• Nuche-Berenguer B, Moreno P, Portal-Nunez S, et al. Exendin-4 exerts osteogenic actions in insulin-resistant and type 2 diabetic states. Regul Pept 2010;159(1-3):61-6
   PubMedGoogle Scholar
• Kyle KA, Willett TL, Baggio LL, et al. Differential effects of PPAR-{gamma} activation versus chemical or genetic reduction of DPP-4 activity on bone quality in mice. Endocrinology 2011;152(2):457-67
   PubMedGoogle Scholar
• Bunck MC, Eliasson B, Cornér A, et al. Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes. Diabetes Obes Metab 2011;13(4):374-7
   PubMedGoogle Scholar
• Monami M, Dicembrini I, Antenore A, Mannucci E. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care 2011;34(11):2474-6
   PubMed Web of Science ®Google Scholar
• Ayaori M, Iwakami N, Uto-Kondo H, et al. Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients. J Am Heart Assoc 2013;2(1):e003277
   Google Scholar
• DeFronzo RA, Okerson T, Viswanathan P, et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin 2008;24(10):2943-52
   PubMed Web of Science ®Google Scholar
• Reid T, Choosing GLP-1 receptor agonists or DPP-4 inhibitors: weighing the clinical trial evidence. Clin Diabetes 2012;30(1):3-12
   Google Scholar
• Liu SC, Tu YK, Chien MN, Chien KL. Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis. Diabetes Obes Metab 2012;14(9):810-20
   PubMed Web of Science ®Google Scholar
• Sitagliptin cardiovascular outcome study (MK-0431-082) (TECOS). Available from: http://clinicaltrials.gov/show/NCT00790205
   Google Scholar
• CARMELINA: cardiovascular and renal microvascular outcome study with linagliptin in patients with type 2 diabetes mellitus at high vascular risk. Available from: http://clinicaltrials.gov/show/NCT01897532
   Google Scholar
• Saxagliptin and atherosclerosis (SAXATH). Available from: http://clinicaltrials.gov/show/NCT01552018
   Google Scholar
• SAFEGUARD: pleiotropic effects of incretin based therapies. Available from: http://clinicaltrials.gov/show/NCT01744236
   Google Scholar
• CAROLINA: cardiovascular outcome study of linagliptin versus glimepiride in patients with type 2 diabetes. Available from: http://clinicaltrials.gov/show/NCT01243424
   Google Scholar
• Effects of vildagliptin/metformin combination on markers of atherosclerosis, thrombosis, and inflammation in diabetics with coronary artery disease (VAAST). Available from: http://clinicaltrials.gov/show/NCT01604213
   Google Scholar
• Exenatide study of cardiovascular event lowering trial (exscel): a trial to evaluate cardiovascular outcomes after treatment with exenatide once weekly in patients with type 2 diabetes mellitus. Available from: http://clinicaltrials.gov/show/NCT01144338
   Google Scholar
• Liraglutide Effect and Action in Diabetes: evaluation of Cardiovascular Outcome Results - A Long Term Evaluation (LEADER®). Available from: http://clinicaltrials.gov/show/NCT01179048
   Google Scholar
• Evaluation of cardiovascular outcomes in patients with type 2 diabetes after acute coronary syndrome during treatment with ave0010 (lixisenatide) (ELIXA). Available from: http://clinicaltrials.gov/show/NCT01147250
   Google Scholar
• Researching cardiovascular events with a weekly incretin in diabetes (REWIND). Available from: http://clinicaltrials.gov/show/NCT01394952
   Google Scholar
• A Study to Evaluate cardiovascular outcomes in patients with type 2 diabetes treated with ITCA 650. Available from: http://clinicaltrials.gov/show/NCT01455896
   Google Scholar
• The Effect of liraglutide on the treatment of coronary artery disease and type 2 diabetes (AddHope2). Available from: http://clinicaltrials.gov/show/NCT01595789
   Google Scholar
• During MJ, Cao L, Zuzga DS, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003;9(9):1173-9
   PubMed Web of Science ®Google Scholar
• Iwai T, Suzuki M, Kobayashi K, et al. The influences of juvenile diabetes on memory and hippocampal plasticity in rats: improving effects of glucagon-like peptide-1. Neurosci Res 2009;64(1):67-74
   PubMed Web of Science ®Google Scholar
• Wang XH, Li L, Hölscher C, et al. Val8-glucagon-like peptide-1 protects against A β1-40-induced impairment of hippocampal late-phase long-term potentiation and spatial learning in rats. Neuroscience 2010;170(4):1239-48
   PubMed Web of Science ®Google Scholar
• Isacson R, Nielsen E, Dannaeus K, et al. The glucagon-like peptide 1 receptor agonist exendin-4 improves reference memory performance and decreases immobility in the forced swim test. Eur J Pharmacol 2011;650(1):249-55
   PubMed Web of Science ®Google Scholar
• Kinzig KP, D’Alessio DA, Herman JP, et al. CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors. J Neurosci 2003;23(15):6163-70
   PubMed Web of Science ®Google Scholar
• Identifying potential effects of liraglutide on degenerative changes. Available from: http://clinicaltrials.gov/show/NCT01469351
   Google Scholar
• A Pilot clinical trial of exendin-4 in Alzheimer’s disease. Available from: http://clinicaltrials.gov/show/NCT01255163
   Google Scholar
• Exendin-4 as a treatment for Parkinson’s disease - pilot study. Available from: http://clinicaltrials.gov/show/NCT01174810
   Google Scholar
• Liraglutide effects on memory in healthy subjects. Available from: http://clinicaltrials.gov/show/NCT01550653
   Google Scholar
• Changes in bone turnover with increased incretin hormone exposure (DRTC). Available from: http://clinicaltrials.gov/show/NCT01374568
   Google Scholar
• Effect of anti-diabetic drugs on bone metabolism and glycemic variability (BoneGlyc). Available from: http://clinicaltrials.gov/show/NCT01679899
   Google Scholar
• Changes in bone turnover with exposure to a glp-1 receptor agonist (CMBD). Available from: http://clinicaltrials.gov/show/NCT01381926
   Google Scholar