Effect of Dapagliflozin on Nighttime Blood Pressure in Type 2 Diabetes

Summary

Centres: Three university hospitals and the primary care centres in their area in Madrid (Clínico San Carlos, La Paz, 12 de Octubre) Type of study: Randomized, multicentric, placebo-controlled, single-blind pilot study Main outcome: Nighttime blood pressure in type 2 diabetic patients Objective: To investigate the effect of the addition of 10 mg daily of dapagliflozin to the treatment of diabetic patients compared to the addition of placebo on the change in nighttime blood pressure (measured by ABPM) over 12 weeks among patients withalbuminuria levels ≥ 30 and \< 3000 mg/g creatinine and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2.. Patients: 225 patients with a previous diagnosis of type 2 diabetes and eGFR\> 30mL/min x1,73m2, office BP above 140/70 mmHg, HbA1C 7.5-10%, albuminuria levels between 30 mg/g creatinine and 3000 mg/g creatinine and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2. Intervention: 10 mg once daily of dapagliflozin or placebo resembling dapagliflozin.

Timeline

Start

2019-04-12

Primary completion

2020-02

Completion

2020-02

Publications

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• Background Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De Buyzere M, De Geest S, Derumeaux GA, Erdine S, Farsang C, Funck-Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Ryden L, Sirenko Y, Stanton A, Struijker-Boudier H, Tsioufis C, van de Borne P, Vlachopoulos C, Volpe M, Wood DA. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013 Jul;34(28):2159-219. doi: 10.1093/eurheartj/eht151. Epub 2013 Jun 14. No abstract available.
• Background Ruilope LM. Current challenges in the clinical management of hypertension. Nat Rev Cardiol. 2011 Oct 25;9(5):267-75. doi: 10.1038/nrcardio.2011.157.
• Background Ruiz-Hurtado G, Ruilope LM, de la Sierra A, Sarafidis P, de la Cruz JJ, Gorostidi M, Segura J, Vinyoles E, Banegas JR. Association Between High and Very High Albuminuria and Nighttime Blood Pressure: Influence of Diabetes and Chronic Kidney Disease. Diabetes Care. 2016 Oct;39(10):1729-37. doi: 10.2337/dc16-0748. Epub 2016 Aug 11.
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• Background Andrassy KM. Comments on 'KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease'. Kidney Int. 2013 Sep;84(3):622-3. doi: 10.1038/ki.2013.243. No abstract available.
• Background Rajasekeran H, Lytvyn Y, Cherney DZ. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. Kidney Int. 2016 Mar;89(3):524-6. doi: 10.1016/j.kint.2015.12.038.
• Background 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.
• Background Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis. Diabetes Care. 2016 Jul;39(7):1108-14. doi: 10.2337/dc16-0330.
• Background Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.
• Background Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.
• Background Imprialos KP, Sarafidis PA, Karagiannis AI. Sodium-glucose cotransporter-2 inhibitors and blood pressure decrease: a valuable effect of a novel antidiabetic class? J Hypertens. 2015 Nov;33(11):2185-97. doi: 10.1097/HJH.0000000000000719.
• Background Weber MA, Mansfield TA, Cain VA, Iqbal N, Parikh S, Ptaszynska A. Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Diabetes Endocrinol. 2016 Mar;4(3):211-220. doi: 10.1016/S2213-8587(15)00417-9. Epub 2015 Nov 27.
• Background Parati G, Stergiou G, O'Brien E, Asmar R, Beilin L, Bilo G, Clement D, de la Sierra A, de Leeuw P, Dolan E, Fagard R, Graves J, Head GA, Imai Y, Kario K, Lurbe E, Mallion JM, Mancia G, Mengden T, Myers M, Ogedegbe G, Ohkubo T, Omboni S, Palatini P, Redon J, Ruilope LM, Shennan A, Staessen JA, vanMontfrans G, Verdecchia P, Waeber B, Wang J, Zanchetti A, Zhang Y; European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014 Jul;32(7):1359-66. doi: 10.1097/HJH.0000000000000221.
• Background Cerezo C, Ruilope LM, Segura J, Garcia-Donaire JA, de la Cruz JJ, Banegas JR, Waeber B, Rabelink TJ, Messerli FH. Microalbuminuria breakthrough under chronic renin-angiotensin-aldosterone system suppression. J Hypertens. 2012 Jan;30(1):204-9. doi: 10.1097/HJH.0b013e32834d9e0f.
• Background Ruiz-Hurtado G, Condezo-Hoyos L, Pulido-Olmo H, Aranguez I, Del Carmen Gonzalez M, Arribas S, Cerezo C, Segura J, Praga M, Fernandez-Alfonso MS, Ruilope LM. Development of albuminuria and enhancement of oxidative stress during chronic renin-angiotensin system suppression. J Hypertens. 2014 Oct;32(10):2082-91; discussion 2091. doi: 10.1097/HJH.0000000000000292.
• Background Pulido-Olmo H, Garcia-Prieto CF, Alvarez-Llamas G, Barderas MG, Vivanco F, Aranguez I, Somoza B, Segura J, Kreutz R, Fernandez-Alfonso MS, Ruilope LM, Ruiz-Hurtado G. Role of matrix metalloproteinase-9 in chronic kidney disease: a new biomarker of resistant albuminuria. Clin Sci (Lond). 2016 Apr 1;130(7):525-38. doi: 10.1042/CS20150517. Epub 2016 Jan 5.
• Background Baldan-Martin M, de la Cuesta F, Alvarez-Llamas G, Gonzalez-Calero L, Ruiz-Hurtado G, Moreno-Luna R, Mourino-Alvarez L, Sastre-Oliva T, Segura J, Padial LR, Vivanco F, Ruilope LM, Barderas MG. Prediction of development and maintenance of high albuminuria during chronic renin-angiotensin suppression by plasma proteomics. Int J Cardiol. 2015 Oct 1;196:170-7. doi: 10.1016/j.ijcard.2015.05.148. Epub 2015 May 29.
• Background Baldan-Martin M, Mourino-Alvarez L, Gonzalez-Calero L, Moreno-Luna R, Sastre-Oliva T, Ruiz-Hurtado G, Segura J, Lopez JA, Vazquez J, Vivanco F, Alvarez-Llamas G, Ruilope LM, de la Cuesta F, Barderas MG. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators. Hypertension. 2016 Jul;68(1):157-66. doi: 10.1161/HYPERTENSIONAHA.116.07412. Epub 2016 May 23.
• Background de la Cuesta F, Baldan-Martin M, Mourino-Alvarez L, Sastre-Oliva T, Alvarez-Llamas G, Gonzalez-Calero L, Ruiz-Hurtado G, Segura J, Vivanco F, Ruilope LM, Barderas MG. [Cardiovascular risk study in patients with renin-angiotensin system blockade by means of the proteone of circulating extracellular vesicles]. Hipertens Riesgo Vasc. 2016 Jan-Mar;33(1):21-7. doi: 10.1016/j.hipert.2015.07.003. Epub 2015 Sep 19. Spanish.
• Background Wei W, Tolle M, Zidek W, van der Giet M. Validation of the mobil-O-Graph: 24 h-blood pressure measurement device. Blood Press Monit. 2010 Aug;15(4):225-8. doi: 10.1097/MBP.0b013e328338892f.

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Indications