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Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication
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In the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin, blood pressure (BP), and weight versus placebo in patients with type 2 diabetes mellitus and hypertension. Patients received placebo (n=271), empagliflozin 10 mg (n=276), or empagliflozin 25 mg (n=276) for 12 weeks (n=full analysis set). This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP (SBP) and diastolic BP (DBP) in patients receiving 0, 1, or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Compared with placebo, empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 (10 mg: −3.89/−2.58 mm Hg; 25 mg: −3.77/−2.45 mm Hg), 1 (10 mg: −4.74/−1.97 mm Hg; 25 mg: −4.27/−1.81 mm Hg), or ≥2 (10 mg: −2.36/−0.68 mm Hg; 25 mg: −4.17/−1.54 mm Hg) antihypertensives. The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP (interaction P value 0.448) or DBP (interaction P value 0.498). Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, with no significant difference between subgroups by use/no use of diuretics (interaction P values 0.380 [systolic]; 0.240 [diastolic]) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (interaction P values 0.900 [systolic]; 0.359 [diastolic]). In conclusion, in patients with type 2 diabetes mellitus and hypertension, empagliflozin for 12 weeks reduced SBP and DBP versus placebo, irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Clinical Trial Registration—: URL: https://clinicaltrials.gov . Unique identifier: NCT01370005.
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“The selection of medications to lower BP in persons with T2D should be guided by individual-specific considerations and may include nontraditional BP-lowering agents such as SGLT2is and GLP-1 RAs, though these drugs alone may be inadequate to control BP.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [241]
Experimental — accuracy not yet measuredIn the citing paper
“In the EMPA-REG BP trial, empagliflozin reduced mean 24 hour ambulatory systolic BP by approximately 3-4 mmHg after 12 weeks, 16 with consistent reductions irrespective of the number of background BP lowering drugs.17”
From Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial (2021) · cites this paper as [17]
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Tran, K. C., & Hiremath, S. S. (2020) · American Journal of Hypertension · doi:10.1093/ajh/hpaa100 · Cited by 12
Cai, Y., Shi, W., & Xu, G. (2020) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2020.1817378 · Cited by 11
SGLT2 Inhibitors in the Management of Cardio-Renal-Metabolic Syndrome: A New Therapeutic Era
Grigoriou, K., Karakasis, P., Nasoufidou, A., Stachteas, P., Klisic, A. N., Karagiannidis, E., Fyntanidou, B., Popovic, D. S., Patoulias, D., Antoniadis, A. P., et al. (2025) · Medicina · doi:10.3390/medicina61111903 · Cited by 14
“For patients on two or more antihypertensives, decreases were − 2.36/ − 0.68 mm Hg (10 mg) and − 4.17/ − 1.54 mm Hg (25 mg) [97].”
InfluentialAazar, R. F. M., Arzouni, R., & Nicolaou, P. A. (2026) · Biomedicines · doi:10.3390/biomedicines14010101 · Cited by 12
“In the EMPA-REG BP trial (n = 824), post hoc analysis showed that empagliflozin lowered systolic and diastolic BP similarly regardless of the number of background antihypertensives and whether ACEI or ARB was used, in patients with T2D and hypertension [10].”
InfluentialJohn, E. E., Travlos, C. K., Luu, J., Lemay, S., Suri, R. S., & Mavrakanas, T. A. (2025) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.0000000693 · Cited by 10
Gouda, M., Arakawa, K., Inagaki, M., & Ushirogawa, Y. (2022) · Journal of Diabetes Investigation · doi:10.1111/jdi.13887 · Cited by 10
Yandrapalli, S., Malik, A. H., Horblitt, A. M., Pemmasani, G., Aronow, W. S., & Frishman, W. H. (2020) · Cardiology in Review · doi:10.1097/crd.0000000000000311 · Cited by 9
“An analysis of the EMPA-REG-BP trial that assessed the effect of background antihypertensive treatment on changes in systolic BP and diastolic BP demonstrated that empagliflozin for 12 weeks reduced systolic BP and diastolic BP versus placebo, irrespective of the number and type of antihypertensives used.(70) SGLT-2 i…”
MethodAn evaluation of empagliflozin and it’s applicability to hypertension as a therapeutic option
Herat, L. Y., Matthews, V. B., Magno, A. L., Kiuchi, M. G., Carnagarin, R., & Schlaich, M. P. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1751815 · Cited by 10
“and DBP compared to placebo, irrespective of the number of anti-hypertensives taken [68].”
BackgroundMethodArterial Hypertension: Novel Pharmacological Targets and Future Perspectives
Popa, I. P., Clim, A., Pînzariu, A. C., Lazăr, C. I., Popa, Ș., Tudorancea, I. M., Moscalu, M., Șerban, D. N., Șerban, I. L., Costache-Enache, I.-I., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13195927 · Cited by 10
“Empagliflozin appears to lower night-time BP to a smaller degree than daytime or 24-h SBP and DBP without a rise in heart rate (HR) and regardless of the administration of a diuretic or ACE/ARB [56].”
BackgroundFeng, Q., Wu, M., & Mai, Z. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1482918 · Cited by 12
Gliflozins in hypertension: basic mechanisms and clinical insights
Rieg, T., Liu, R., & Staruschenko, A. (2025) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00119.2025 · Cited by 10
Rizos, C. V., Filippatos, T. D., & Elisaf, M. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2018.1418325 · Cited by 10
“The neutral effects of linagliptin together with the beneficial effects of empagliflozin on weight and blood pressure are expected to result in overall additional benefits for the patient [79,80].”
BackgroundAlqudsi, M., Velez, J. C. Q., & Navarrete, J. E. (2021) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000865 · Cited by 9
“Interestingly, patients with baseline 24-h BP 130/ 80 mmHg had greater decline of BP, whereas empagliflozin dosage and number of antihypertensive agents at baseline did not make a difference [21,22].”
BackgroundRisk of heart failure in ambulatory resistant hypertension: a meta-analysis of observational studies
Coccina, F., Salles, G. F., Banegas, J. R., Hermida, R. C., Bastos, J. M., Cardoso, C. R. L., Salles, G. C., Sánchez-Martínez, M., Mojón, A., Fernández, J. R., et al. (2024) · Hypertension Research · doi:10.1038/s41440-024-01632-8 · Cited by 7
Tanaka, A., Shimabukuro, M., Teragawa, H., Yoshida, H., Okada, Y., Takamura, T., Taguchi, I., Toyoda, S., Tomiyama, H., Ueda, S., et al. (2024) · Hypertension Research · doi:10.1038/s41440-024-01725-4 · Cited by 8
Ambulatory Resistant Hypertension and Risk of Heart Failure in the Elderly
Coccina, F., Pierdomenico, A. M., Cuccurullo, C., Pizzicannella, J., Trubiani, O., & Pierdomenico, S. D. (2023) · Diagnostics · doi:10.3390/diagnostics13091631 · Cited by 8
“Moreover, in the EMPA-REG BP trial [49], it has been shown that the addition of empaglifozin further reduces 24-h systolic/diastolic BP (about 4 mmHg/2 mmHg) irrespective of the number and type of antihypertensive drug used.”
BackgroundThomopoulos, C., Bazoukis, G., Ilias, Ι., Tsioufis, C. P., & Makris, T. (2019) · Journal of Hypertension · doi:10.1097/hjh.0000000000002152 · Cited by 7
“However, newer antidiabetic agents such glucagon-like peptide 1 agonists and inhibitors of the sodium-glucose cotransporter 2 may exert a BP-lowering effect by independent of glucose-lowering mechanisms such as increased weight loss, potentiated natriuresis and vasodilation [42,43].”
BackgroundAronow, W. S., & Shamliyan, T. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2017.08.43 · Cited by 7
“Efficacy Moderate-quality evidence suggests that empagliflozin reduces all-cause mortality (7,11,40,44,46,47,49-61) and increases the rates of diabetes control without increasing the risk of serious adverse effects and hypoglycemia when compared with placebo in adults with type 2 diabetes (Table 1) (50,51,70).”
BackgroundYu, T., Xiao, J., Li, M., Cheng, S., Cai, R., Huang, L., Yu, H., Li, J. Y., Zhang, Y.-Y., & Wang, Y. (2025) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2025.2471529 · Cited by 5
“The EMPA-REG BP trial and others noted that SGLT2i can lower blood pressure during treatment [46,47].”
Gitto, M., Vrachatis, D. A., Condorelli, G., Papathanasiou, K. A., Reimers, B., Deftereos, S. G., & Stefanini, G. G. (2021) · Cardiovascular & Hematological Agents in Medicinal Chemistry · doi:10.2174/1871525719666210809121016 · Cited by 5
Blood glucose and hypertension development
Nilsson, P. M. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001946 · Cited by 5
Blood Pressure-Lowering Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists
Siddiqi, A. K., Khan, M. S., Kulkarni, A., Hall, M. E., Böhm, M., Dı́ez, J., & Butler, J. (2025) · Current Hypertension Reports · doi:10.1007/s11906-025-01342-7 · Cited by 4
“Addi - tionally, a subgroup analysis of the EMPA-REG trial examined the BP-lowering effects of empagliflozin relative to the number of antihypertensive medications used at baseline [ 38].”
InfluentialThe anti-hypertensive effects of sodium-glucose cotransporter-2 inhibitors
Kugathasan, L., Dubrofsky, L., Advani, A., & Cherney, D. Z. I. (2022) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2023.2159810 · Cited by 5
Hitting the Sweet Spot: A Review of SGLT2i in Cardiovascular Medicine
Zayyad, Z. A., Gupta, N., Roy, A., Kalagara, S., Mishra, A., Salem, E., Seshadri, S. R., Gichi, D., Hammad, B., Ene, A., et al. (2025) · Cardiology and Therapy · doi:10.1007/s40119-025-00436-2 · Cited by 4
“Results from this trial suggested additional mechanisms of action of BP reduction by SGLT2i beyond glucosuria, such as osmotic diuresis, weight loss, and reduced arterial stiffness [22].”
Orthostatic Hypotension and Diabetes
Cuspidi, C., Gherbesi, E., Sala, C., & Tadic, M. V. (2023) · Updates in hypertension and cardiovascular protection · doi:10.1007/978-3-031-13009-0_29 · Cited by 2
New Potential Treatments for Resistant Hypertension
Janakiraman, A., & Cohen, D. L. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01966-8 · Cited by 3
“This was further demonstrated by Mancia et al. [24], where empagliflozin (10-25 mg daily) reduced 24-h SBP and DBP by 3–4 mmHg and 1–2 mmHg, respectively.”
ResultAsanuma, H. (2024) · Hypertension Research · doi:10.1038/s41440-024-01793-6 · Cited by 3
“Furthermore, it has been reported that in patients with T2DM and hypertension, empagli fl ozin reduced systolic BP and diastolic BP versus placebo, irrespective of the use of background number of anti-hypertensives agents [7].”
Belančić, A., Şener, Y. Z., Vučković, M., Blais, J. E., Fajkić, A., Sher, E. K., Radić, M., & Radić, J. (2025) · British Journal of Clinical Pharmacology · doi:10.1002/bcp.70378 · Cited by 2
Ito, R., Satoh, M., Hashimoto, H., Nobayashi, H., Izumi, S., Toyama, M., Iwabe, Y., Suzuki, Y., Hirose, T., Nakayama, S., et al. (2026) · Journal of Clinical Hypertension · doi:10.1111/jch.70214 · Cited by 2
Dapagliflozin improves cardiovascular risk factors in Emirati patients with T2DM
Nada, A. M., & Younan, M. A. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018821995364 · Cited by 2
SGLT-2 Inhibitors: The Magic Bullet for Cardio-Renal Protection in Type 2 DM
Patel, R., & Oroszi, T. L. (2024) · Pharmacology & Pharmacy · doi:10.4236/pp.2024.1512027 · Cited by 1
Russo, E., Cappadona, F., Macciò, L., Vincenzo, J. D., Piaggio, M., Verzola, D., Chirco, G., Garibotto, G., Esposito, P. B., & Viazzi, F. C. (2025) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-025-00764-3 · Cited by 1
“Empagliflozin also decreased BP after 12 weeks, with efficacy preserved despite renal function decline and irrespective of background therapy [6].”
Özhan, O., Çolak, M., Karaca, E., Dogru, F., Küçükakçalı, Z., Acet, A., & Parlakpınar, H. (2026) · Journal of Molecular Histology · doi:10.1007/s10735-025-10708-9 · Cited by 1
“The myocardium has a high mitochondrial density and oxygen consumption in 2016, Mancia et al. (2016 ) observed that EMPA provided a decrease in systolic and diastolic BP values.”
Metadata
- Authors
- Mancia, G., Cannon, C. P., Tikkanen, I., Zeller, C., Ley, L., Woerle, H. J., Broedl, U. C., & Johansen, O. E.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Hypertension
- Published
- 2016-12
- Volume
- 68
- Issue
- 6
- Pages
- 1355-1364
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2530979034
- Cited by
- 128
- References
- 33
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 12 · 2023: 14 · 2022: 11 · 2021: 20 · 2020: 16 · 2019: 15 · 2018: 12 · 2017: 6 · 2016: 1
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Alnylam Pharmaceuticals
- Regeneron Pharmaceuticals
- Kowa Company
- Servier
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- empagliflozin, type 2 diabetes, blood pressure reduction, antihypertensive drugs, diuretics, ACE inhibitors, angiotensin receptor blockers, 24-hour ambulatory blood pressure, SGLT2 inhibitors, subgroup analysis, dose comparison, weight loss, glycohemoglobin
- MeSH terms
- Antihypertensive Agents, Benzhydryl Compounds, Blood Glucose, Blood Pressure Determination, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Glucosides, Humans, Hypertension, Hypoglycemic Agents, Male, Prospective Studies, Reference Values, Severity of Illness Index, Comorbidity, Treatment Outcome
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