Effect of Dapagliflozin on the Progression From Prediabetes to T2DM in Subjects With Myocardial Infarction

Summary

It is hypothesize that, because dapagliflozin will reverse the metabolic defects responsible for the development of prediabetes (i.e. insulin resistance and beta cell dysfunction) and progression from prediabetes to T2DM (beta cell dysfunction) and will cause weight loss, it will markedly reduce the progression from prediabetes to T2DM and reverse glucose tolerance to NGT in patients with prediabetes experiencing acute myocardial infarction. Further, it is hypothesized that the hemodynamic actions of dapagliflzoin will exert cardiovascular benefit in subjects with prediabetes and acute MI by reducing cardiac remodeling, preserve LV function and decrease the risk of development of heart failure and hospitalization for heart failure. Hence, aim to examine the impact of SGLT2 inhibitor on T2DM and cardiovascular risk in patients with prediabetes and cardiovascular disease. The primary objective of the study is to examine the effect of dapagliflozin (10 mg) on the progression from prediabetes to T2DM in patients with prediabetes who experience acute myocardial infarction (MI). A secondary objective is to examine the effect of dapagliflozin on a composite of CV outcome including incidence and hospitalization for heart failure in patients with prediabetes with acute MI. Other secondary outcome is the change from baseline to end of study in LD systolic and diastolic function.

Timeline

Start

2019-03-01

Primary completion

2020-12-31

Completion

2021-01-31

Publications

• Results Abdul-Ghani M, Migahid O, Megahed A, Singh R, Kamal D, DeFronzo RA, Jayyousi A. Insulin secretion predicts the response to therapy with exenatide plus pioglitazone, but not to basal/bolus insulin in poorly controlled T2DM patients: Results from the Qatar study. Diabetes Obes Metab. 2018 Apr;20(4):1075-1079. doi: 10.1111/dom.13189. Epub 2018 Jan 15.
• Results Abdul-Ghani MA, DeFronzo RA. Pathophysiology of prediabetes. Curr Diab Rep. 2009 Jun;9(3):193-9. doi: 10.1007/s11892-009-0032-7.
• Results Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, Kitzmiller J, Knowler WC, Lebovitz H, Lernmark A, Nathan D, Palmer J, Rizza R, Saudek C, Shaw J, Steffes M, Stern M, Tuomilehto J, Zimmet P; Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003 Nov;26(11):3160-7. doi: 10.2337/diacare.26.11.3160. No abstract available.
• Results Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care. 2006 May;29(5):1130-9. doi: 10.2337/diacare.2951130.
• Results Dankner R, Abdul-Ghani MA, Gerber Y, Chetrit A, Wainstein J, Raz I. Predicting the 20-year diabetes incidence rate. Diabetes Metab Res Rev. 2007 Oct;23(7):551-8. doi: 10.1002/dmrr.728.
• Results Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013 Sep;15(9):853-62. doi: 10.1111/dom.12127. Epub 2013 Jun 5.
• Results Al-Lawati JA, Sulaiman KJ, Al-Zakwani I, Alsheikh-Ali AA, Panduranga P, Al-Habib KF, Al-Suwaidi J, Al-Mahmeed W, Al-Faleh H, El-Asfar A, Al-Motarreb A, Ridha M, Bulbanat B, Al-Jarallah M, Bazargani N, Asaad N, Amin H. Systolic Blood Pressure on Admission and Mortality in Patients Hospitalized With Acute Heart Failure: Observations From the Gulf Acute Heart Failure Registry. Angiology. 2017 Aug;68(7):584-591. doi: 10.1177/0003319716672525. Epub 2016 Oct 7.
• Results Sulaiman K, Panduranga P, Al-Zakwani I, Alsheikh-Ali AA, AlHabib KF, Al-Suwaidi J, Al-Mahmeed W, AlFaleh H, Elasfar A, Al-Motarreb A, Ridha M, Bulbanat B, Al-Jarallah M, Bazargani N, Asaad N, Amin H. Clinical characteristics, management, and outcomes of acute heart failure patients: observations from the Gulf acute heart failure registry (Gulf CARE). Eur J Heart Fail. 2015 Apr;17(4):374-84. doi: 10.1002/ejhf.245. Epub 2015 Mar 4.
• Results Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA, Zirie M, Jayyousi A. Erratum. Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study. Diabetes Care 2017;40:325-331. Diabetes Care. 2017 Aug;40(8):1134. doi: 10.2337/dc17-er08d. Epub 2017 Jun 14. No abstract available.
• Results Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA, Zirie M, Jayyousi A. Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study. Diabetes Care. 2017 Mar;40(3):325-331. doi: 10.2337/dc16-1738. Epub 2017 Jan 17.
• Results Abdul-Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab. 2015 Mar;17(3):268-75. doi: 10.1111/dom.12417. Epub 2015 Jan 7.
• Results Verma S, Garg A, Yan AT, Gupta AK, Al-Omran M, Sabongui A, Teoh H, Mazer CD, Connelly KA. Effect of Empagliflozin on Left Ventricular Mass and Diastolic Function in Individuals With Diabetes: An Important Clue to the EMPA-REG OUTCOME Trial? Diabetes Care. 2016 Dec;39(12):e212-e213. doi: 10.2337/dc16-1312. Epub 2016 Sep 27. No abstract available.
• Results Oliva RV, Bakris GL. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors. J Am Soc Hypertens. 2014 May;8(5):330-9. doi: 10.1016/j.jash.2014.02.003. Epub 2014 Feb 12.
• Results Al-Jobori H, Daniele G, Cersosimo E, Triplitt C, Mehta R, Norton L, DeFronzo RA, Abdul-Ghani M. Empagliflozin and Kinetics of Renal Glucose Transport in Healthy Individuals and Individuals With Type 2 Diabetes. Diabetes. 2017 Jul;66(7):1999-2006. doi: 10.2337/db17-0100. Epub 2017 Apr 20.

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