Dapagliflozin, Cardio-Metabolic Risk Factors and Type-2 Diabetes

Summary

Dapagliflozin is a member of the sodium-glucose cotransporter-2 (SGLT2) inhibitor class antidiabetes agents which produces significant and sustained reductions in glycemic parameters in patients with type 2 diabetes (T2DM). However, its non-glycemic effects are still largely unknown. The investigators will evaluate for the first time the effect of dapagliflozin on multiple cardio-metabolic risk markers in one study. So far, no data on the effects of dapagliflozin as well as other SGLT-2 inhibitors on subclinical atherosclerosis, endothelial function, inflammatory markers, cytokines and atherogenic lipoproteins is available. In addition, the investigators will examine microRNAs (miRNAs) implicated in the development and progression of atherosclerotic disease. Again, no data is currently available on dapaglifozin's as well as other SGLT-2 inhibitors' effects on miRNAs. The results of this study will show for the first time the potential multiple, non-glycemic effects of dapagliflozin, reducing multiple cardio-metabolic risk markers, which will ultimately lead to decreased CV risk. In addition, specific mechanisms of the dapagliflozin cardiovascular action will be investigated. Finally, the results of this study may pave the way for personalized therapy (using the results on miRNAs).

Timeline

Start

2017-12-22

Primary completion

2018-12

Completion

2019-01

Publications

• Background Rizzo M, Rizvi AA, Patti AM, Nikolic D, Giglio RV, Castellino G, Li Volti G, Caprio M, Montalto G, Provenzano V, Genovese S, Ceriello A. Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study. Cardiovasc Diabetol. 2016 Dec 3;15(1):162. doi: 10.1186/s12933-016-0480-8.
• Background Rizzo M, Chandalia M, Patti AM, Di Bartolo V, Rizvi AA, Montalto G, Abate N. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol. 2014 Feb 22;13:49. doi: 10.1186/1475-2840-13-49.
• Background Corrado E, Rizzo M, Coppola G, Muratori I, Carella M, Novo S. Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: a 24-month follow-up study. Coron Artery Dis. 2008 May;19(3):139-44. doi: 10.1097/MCA.0b013e3282f3fbde.
• Background Salamone F, Galvano F, Marino Gammazza A, Paternostro C, Tibullo D, Bucchieri F, Mangiameli A, Parola M, Bugianesi E, Li Volti G. Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis. Dig Liver Dis. 2012 Apr;44(4):334-42. doi: 10.1016/j.dld.2011.11.010. Epub 2011 Dec 24.
• Background Rizzo M, Abate N, Chandalia M, Rizvi AA, Giglio RV, Nikolic D, Marino Gammazza A, Barbagallo I, Isenovic ER, Banach M, Montalto G, Li Volti G. Liraglutide reduces oxidative stress and restores heme oxygenase-1 and ghrelin levels in patients with type 2 diabetes: a prospective pilot study. J Clin Endocrinol Metab. 2015 Feb;100(2):603-6. doi: 10.1210/jc.2014-2291. Epub 2014 Nov 13.
• Background Berneis K, Rizzo M, Berthold HK, Spinas GA, Krone W, Gouni-Berthold I. Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial. Eur Heart J. 2010 Jul;31(13):1633-9. doi: 10.1093/eurheartj/ehq181. Epub 2010 Jun 6.
• Background Mikhailidis DP, Elisaf M, Rizzo M, Berneis K, Griffin B, Zambon A, Athyros V, de Graaf J, Marz W, Parhofer KG, Rini GB, Spinas GA, Tomkin GH, Tselepis AD, Wierzbicki AS, Winkler K, Florentin M, Liberopoulos E. "European panel on low density lipoprotein (LDL) subclasses": a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses. Curr Vasc Pharmacol. 2011 Sep;9(5):533-71. doi: 10.2174/157016111796642661.
• Background Barbagallo I, Parenti R, Zappala A, Vanella L, Tibullo D, Pepe F, Onni T, Li Volti G. Combined inhibition of Hsp90 and heme oxygenase-1 induces apoptosis and endoplasmic reticulum stress in melanoma. Acta Histochem. 2015 Oct;117(8):705-11. doi: 10.1016/j.acthis.2015.09.005. Epub 2015 Oct 19.
• Background Cengiz M, Yavuzer S, Kilickiran Avci B, Yuruyen M, Yavuzer H, Dikici SA, Karatas OF, Ozen M, Uzun H, Ongen Z. Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension. Clin Exp Hypertens. 2015;37(8):643-9. doi: 10.3109/10641963.2015.1036064. Epub 2015 Jun 26.
• Background Tziomalos K, Athyros VG, Karagiannis A. Editorial: Vascular Calcification, Cardiovascular Risk and microRNAs. Curr Vasc Pharmacol. 2016;14(2):208-10. doi: 10.2174/157016111402160208150816.
• Background Signorelli SS, Volsi GL, Pitruzzella A, Fiore V, Mangiafico M, Vanella L, Parenti R, Rizzo M, Volti GL. Circulating miR-130a, miR-27b, and miR-210 in Patients With Peripheral Artery Disease and Their Potential Relationship With Oxidative Stress. Angiology. 2016 Nov;67(10):945-950. doi: 10.1177/0003319716638242. Epub 2016 Jul 11.
• Background Peng H, Zhong M, Zhao W, Wang C, Zhang J, Liu X, Li Y, Paudel SD, Wang Q, Lou T. Urinary miR-29 correlates with albuminuria and carotid intima-media thickness in type 2 diabetes patients. PLoS One. 2013 Dec 9;8(12):e82607. doi: 10.1371/journal.pone.0082607. eCollection 2013.

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Indications