Efficacy and safety profile of SGLT2 inhibitors in the elderly: how is the benefit/risk balance?
Open accessAbstract
Type 2 diabetes mellitus (T2DM) is a highly prevalent health condition in the aging population. Older adults with T2DM have higher risks of cardiovascular disease, heart failure (long underestimated) and premature death than those without diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven their ability to improve cardiovascular prognosis and reduce the risk of hospitalization for heart failure (hHF). However, several adverse events have been reported, whose incidence and severity might be increased in the elderly population. The aims of this comprehensive review were to analyze the benefit-risk ratio of SGLT2i therapy in older patients with T2DM by collecting data from (i) large prospective placebo-controlled cardiovascular outcome trials (including those dedicated to heart failure), using both original publications and dedicated post-hoc analyses across different age groups and (ii) observational cohort studies, describing the effects of SGLT2is versus other glucose-lowering agents on cardiovascular outcomes and hHF in elderly patients or these effects in different age groups. Overall, consistent results showed a similar relative risk reduction in cardiovascular mortality and hHF with SGLT2is independently of age. The absolute risk reduction may be greater in elderly because of a higher background risk in older versus younger patients. Similarly, the safety profile of SGLT2is appeared comparable in older versus younger patients. In conclusion, the benefit/risk balance favors the use of SGLT2is in older patients at risk of cardiovascular disease and/or heart failure. Caution may be required in very old frail patients, especially those exposed to an increased risk of volume depletion.
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SGLT2 inhibitors may cause clinically significant volume depletion, for which older adults are at greater risk.
“SGLT2 inhibitors may cause clinically significant volume depletion, for which older adults are at greater risk”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [143]
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Sciacqua, A., Succurro, E., Armentaro, G., Miceli, S., Pastori, D., Rengo, G., & Sesti, G. (2021) · Heart Failure Reviews · doi:10.1007/s10741-021-10182-x · Cited by 35 · see citing works
Careful use to minimize adverse events of oral antidiabetic medications in the elderly
Scheen, A. J. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1912735 · Cited by 34 · see citing works
Self-citationScheen, A. J. (2022) · Diabetes & Metabolism · doi:10.1016/j.diabet.2022.101390 · Cited by 34 · see citing works
Self-citationGautam, S., Agiro, A., Barron, J. O., Power, T. P., Weisman, H., & White, J. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0575-x · Cited by 33 · see citing works
Scheen, A. J. (2021) · Diabetes & Metabolism · doi:10.1016/j.diabet.2021.101275 · Cited by 32 · see citing works
Self-citationSGLT2 Inhibitors and Safety in Older Patients
Pollack, R. M., & Cahn, A. (2022) · Heart Failure Clinics · doi:10.1016/j.hfc.2022.03.002 · Cited by 31 · see citing works
Htoo, P. T., Tesfaye, H., Schneeweiß, S., Wexler, D. J., Everett, B. M., Glynn, R. J., Kim, S. C., Najafzadeh, M., Koeneman, L., FARSANI, S. F. F., et al. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.37606 · Cited by 31 · see citing works
Yabe, D., Shiki, K., Suzaki, K., Meinicke, T. W., Kotobuki, Y., Nishida, K., Clark, D., Yasui, A., & Seino, Y. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-045844 · Cited by 30 · see citing works
Fralick, M., Colacci, M., Thiruchelvam, D., Gomes, T., & Redelmeier, D. A. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14300 · Cited by 27 · see citing works
Giorgino, F., Vora, J. P., Fenici, P., & Solini, A. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14055 · Cited by 23 · see citing works
Perez-Belmonte, L. M., Sanz‐Cánovas, J., Millán‐Gómez, M., Osuna‐Sánchez, J., Sampalo, A. L., Ricci, M., Jiménez-Navarro, M. F., Lopez-Carmona, M. D., Bernal-López, M. R., Barbancho, M. Á., et al. (2021) · Journal of the American Geriatrics Society · doi:10.1111/jgs.17585 · Cited by 22 · see citing works
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Scheen, A. J., & Delanaye, P. (2021) · Diabetes & Metabolism · doi:10.1016/j.diabet.2021.101315 · Cited by 21 · see citing works
Self-citationOkada, K., Hoshide, S., Kato, M., Kanegae, H., Ishibashi, S., & Kario, K. (2020) · Journal of Clinical Hypertension · doi:10.1111/jch.14131 · Cited by 19 · see citing works
Eligibility of Dapagliflozin and Empagliflozin in a Real-World Heart Failure Population
Håkansson, E., Norberg, H., Själander, S., & Lindmark, K. (2021) · Cardiovascular Therapeutics · doi:10.1155/2021/1894155 · Cited by 18 · see citing works
Scheen, A. J., & Delanaye, P. (2021) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2022.2014322 · Cited by 18 · see citing works
Self-citationPratley, R. E., Dagogo-Jack, S. E., Charbonnel, B. H., Patel, S. M., Hickman, A., Liu, J., Tarasenko, L. C., Pong, A., Ellison, M. C., Huyck, S. B., et al. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14150 · Cited by 18 · see citing works
Impact of SGLT2 inhibitors on old age patients with heart failure and chronic kidney disease
Amioka, M., Sanada, R., Matsumura, H., Kinoshita, H., Sairaku, A., Morishima, N., & Nakano, Y. (2022) · International Journal of Cardiology · doi:10.1016/j.ijcard.2022.09.059 · Cited by 17 · see citing works
Arnott, C. G., Li, J., Cannon, C. P., de Zeeuw, D., Neuen, B. L., Heerspink, H. J. L., Charytan, D. M., Agarwal, A., Huffman, M. D., Figtree, G. A., et al. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14386 · Cited by 17 · see citing works
The Intersection of SGLT2 Inhibitors, Cognitive Impairment, and CKD
Noel, J. A., Hougen, I., & Sood, M. M. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.823569 · Cited by 15 · see citing works
Nakai, M., Iwanaga, Y., Kanaoka, K., Sumita, Y., Nishioka, Y., Myojin, T., Kubo, S., Okada, K., Soeda, T., Noda, T., et al. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01586-6 · Cited by 15 · see citing works
Desai, R. J., Glynn, R. J., Everett, B. M., Schneeweiß, S., Wexler, D. J., Bessette, L. G., Déruaz‐Luyet, A., Vedin, O., Brodovicz, K. G., & Patorno, E. (2022) · American Heart Journal · doi:10.1016/j.ahj.2022.09.008 · Cited by 15 · see citing works
Inagaki, N., Nangaku, M., Sakata, Y., Sasaki, K., Mori‐Anai, K., Iwasaki, T., & Hamada, K. (2021) · Advances in Therapy · doi:10.1007/s12325-021-01984-4 · Cited by 14 · see citing works
Scheen, A. J. (2022) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2022.2105693 · Cited by 10 · see citing works
Self-citationUsman, M. S., Khan, M. S., Fonarow, G. C., Greene, S. J., Friede, T., Vaduganathan, M., Filippatos, G., Coats, A. J. S., Anker, S. D., & Butler, J. (2022) · ESC Heart Failure · doi:10.1002/ehf2.13785 · Cited by 8 · see citing works
Adams, J., & Mosler, C. (2022) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2022.2098118 · Cited by 6 · see citing works
Berg, D. D., Kolkailah, A. A., Sarraju, A., Kerchberger, A. M., Eljalby, M., & McGuire, D. K. (2021) · Current Diabetes Reports · doi:10.1007/s11892-021-01417-0 · Cited by 4 · see citing works
Empagliflozin and Elderly Patients With Preserved Ejection Fraction Heart Failure
Sauer, A. J. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.04.037 · Cited by 3 · see citing works
Ovalle, F., Dumas, R., Fabbrini, E., Slee, A. E., & Perkovic, V. (2018) · Endocrine Practice · doi:10.1016/s1530-891x(20)47079-x · Cited by 2 · see citing works
Galassi, A., Cara, A., Magagnoli, L., Faccioli, F. M., & Cozzolino, M. G. (2022) · International Journal of Cardiology · doi:10.1016/j.ijcard.2022.10.155 · Cited by 2 · see citing works
Flagged first, then by citations
3 of the 113 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Radholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, et al. Canagliflozin and heart failure in type 2 diabetes mellitus. Circulation 2018;138:458-68.
Cited by
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Navaneethan, S. D., Bansal, N., Cavanaugh, K. L., Chang, A. R., Crowley, S. T., Delgado, C., Estrella, M. M., Ghossein, C., Ikizler, T. A., Koncicki, H. M., et al. (2024) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2024.08.003 · Cited by 108 · see citing works
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mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes
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The current role of SGLT2 inhibitors in type 2 diabetes and beyond: a narrative review
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- Authors
- Scheen, A. J., & Bonnet, F.
- Affiliations
- University of Liège (BE)
- Inserm (FR)
- Corresponding author
- Scheen, André J.
- Venue
- Diabetes & Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-03
- Volume
- 49
- Issue
- 2
- Pages
- 101419
- ISSN
- 1262-3636 (ISSN-L)
- OpenAlex
- W4315647951
- Cited by
- 51
- References
- 113
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 8 · 2023: 9
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- Locations
- Diabetes & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc)
- ORBi (University of Liège) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- SGLT2 inhibitors, type 2 diabetes, older adults, heart failure, cardiovascular outcomes, benefit-risk balance, adverse events, cardiovascular mortality, heart failure hospitalization, frailty, hypovolemia, age differences
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucose, Heart Failure, Humans, Hypoglycemic Agents, Prospective Studies
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