Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Design
  4. Volume 31, Issue 16
  5. Article
Volume 31, Issue 16
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Background

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a valuable treatment for type 2 diabetes (T2D) and heart failure. Despite these medications seeming to be safe in older people, the literature about SGLT2i and frailty is still limited. This study aims to evaluate whether SGLT2i use is associated with increased survival in older adults and if frailty can affect the findings.

Materials and Methods

We enrolled over 65 patients admitted to the Geriatrics Wards at the University Hospital 'P. Giaccone' in Palermo, Italy, between December 2022 and May 2023. After 12 months of follow-up, various outcomes were assessed, including mortality, hospitalization, glycemic dysregulation, urinary tract infections, and falls. The association between SGLT2i use and mortality was analyzed and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs).

Results

A total of 80 patients were included in the study (mean age 79.5 ± 8.5 years; 50% were women). Patients using SGLT2i had a higher prevalence of T2D ( 0.02) and cirrhosis ( 0.001). After adjusting for potential confounders, SGLT2i use was significantly associated with a reduced mortality risk (HR = 0.53; 95% CI: 0.20-0.93; 0.02). When stratified by the presence of multidimensional frailty, SGLT2i use was significantly associated with a lower risk of mortality in frail patients (HR = 0.27; 95% CI: 0.06-0.88; 0.008), but not in robust ones.

Conclusion

In older frail patients, the use of SGLT2i is associated with reduced mortality after 12 months of follow-up. Further larger studies are needed to evaluate the role of these medications in older adults.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128347041241129055001
2025-01-13
2025-06-12

  • From This Site

    /content/journals/cpd/10.2174/0113816128347041241129055001
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BellaryS. KyrouI. BrownJ.E. BaileyC.J. Type 2 diabetes mellitus in older adults: Clinical considerations and management.Nat. Rev. Endocrinol.202117953454810.1038/s41574‑021‑00512‑234172940
     [Google Scholar]
  2. KleinS. GastaldelliA. Yki-JärvinenH. SchererP.E. Why does obesity cause diabetes?Cell Metab.2022341112010.1016/j.cmet.2021.12.01234986330
     [Google Scholar]
  3. SinclairA. SaeediP. KaundalA. KarurangaS. MalandaB. WilliamsR. Diabetes and global ageing among 65–99 year-old adults: Findings from the international diabetes federation diabetes atlas, 9th edition.Diabetes Res. Clin. Pract.202016210807810.1016/j.diabres.2020.10807832068097
     [Google Scholar]
  4. MarillyE. CottinJ. CabreraN. CornuC. BoussageonR. MoulinP. LegaJ.C. GueyffierF. CucheratM. GrenetG. SGLT2 inhibitors in type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials balancing their risks and benefits.Diabetologia202265122000201010.1007/s00125‑022‑05773‑835925319
     [Google Scholar]
  5. SimesB.C. MacGregorG.G. Sodium-glucose cotransporter-2 (SGLT2) inhibitors: A clinician’s guide.Diabetes Metab. Syndr. Obes.2019122125213610.2147/DMSO.S21200331686884
     [Google Scholar]
  6. NealB. PerkovicV. MahaffeyK.W. de ZeeuwD. FulcherG. EronduN. ShawW. LawG. DesaiM. MatthewsD.R. CANVAS Program Collaborative Group Canagliflozin and cardiovascular and renal events in Type 2 diabetes.N. Engl. J. Med.2017377764465710.1056/NEJMoa161192528605608
     [Google Scholar]
  7. PerkovicV. JardineM.J. NealB. BompointS. HeerspinkH.J.L. CharytanD.M. EdwardsR. AgarwalR. BakrisG. BullS. CannonC.P. CapuanoG. ChuP.L. de ZeeuwD. GreeneT. LevinA. PollockC. WheelerD.C. YavinY. ZhangH. ZinmanB. MeiningerG. BrennerB.M. MahaffeyK.W. CREDENCE Trial Investigators Canagliflozin and renal outcomes in Type 2 diabetes and nephropathy.N. Engl. J. Med.2019380242295230610.1056/NEJMoa181174430990260
     [Google Scholar]
  8. WiviottS.D. RazI. BonacaM.P. MosenzonO. KatoE.T. CahnA. SilvermanM.G. ZelnikerT.A. KuderJ.F. MurphyS.A. BhattD.L. LeiterL.A. McGuireD.K. WildingJ.P.H. RuffC.T. Gause-NilssonI.A.M. FredrikssonM. JohanssonP.A. LangkildeA.M. SabatineM.S. DECLARE–TIMI 58 Investigators Dapagliflozin and cardiovascular outcomes in Type 2 diabetes.N. Engl. J. Med.2019380434735710.1056/NEJMoa181238930415602
     [Google Scholar]
  9. ZinmanB. WannerC. LachinJ.M. FitchettD. BluhmkiE. HantelS. MattheusM. DevinsT. JohansenO.E. WoerleH.J. BroedlU.C. InzucchiS.E. EMPA-REG OUTCOME Investigators Empagliflozin, cardiovascular outcomes, and mortality in Type 2 diabetes.N. Engl. J. Med.2015373222117212810.1056/NEJMoa150472026378978
     [Google Scholar]
  10. RossingP. CaramoriM.L. ChanJ.C.N. HeerspinkH.J.L. HurstC. KhuntiK. LiewA. MichosE.D. NavaneethanS.D. OlowuW.A. SaduskyT. TandonN. TuttleK.R. WannerC. WilkensK.G. ZoungasS. CraigJ.C. TunnicliffeD.J. TonelliM.A. CheungM. EarleyA. de BoerI.H. Executive summary of the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease: An update based on rapidly emerging new evidence.Kidney Int.2022102599099910.1016/j.kint.2022.06.01336272755
     [Google Scholar]
  11. FriedL.P. TangenC.M. WalstonJ. NewmanA.B. HirschC. GottdienerJ. SeemanT. TracyR. KopW.J. BurkeG. McBurnieM.A. Cardiovascular Health Study Collaborative Research Group Frailty in older adults: Evidence for a phenotype.J. Gerontol. A Biol. Sci. Med. Sci.2001563M146M15710.1093/gerona/56.3.M14611253156
     [Google Scholar]
  12. CoboA. VázquezL.A. ReviriegoJ. Rodríguez-MañasL. Impact of frailty in older patients with diabetes mellitus: An overview.Endocrinol. Nutr.201663629130310.1016/j.endonu.2016.01.00426971016
     [Google Scholar]
  13. YoonS.J. KimK. Frailty and disability in diabetes.Ann. Geriatr. Med. Res.201923416516910.4235/agmr.19.003632743307
     [Google Scholar]
  14. WongE. BackholerK. GearonE. HardingJ. Freak-PoliR. StevensonC. PeetersA. Diabetes and risk of physical disability in adults: A systematic review and meta-analysis.Lancet Diabetes Endocrinol.20131210611410.1016/S2213‑8587(13)70046‑924622316
     [Google Scholar]
  15. ChenH.L. HsuW.W.Y. HsiaoF.Y. Changes in prevalence of diabetic complications and associated healthcare costs during a 10-year follow-up period among a nationwide diabetic cohort.J. Diabetes Complications201529452352810.1016/j.jdiacomp.2015.02.00225770886
     [Google Scholar]
  16. O’DonovanM. SezginD. O’CaoimhR. LiewA. The impact of and interaction between diabetes and frailty on psychosocial wellbeing and mortality in Ireland.Int. J. Environ. Res. Public Health20201724953510.3390/ijerph1724953533352735
     [Google Scholar]
  17. HickmanE. GilliesC. KhuntiK. SeiduS. Deprescribing, polypharmacy and prescribing cascades in older people with Type 2 diabetes: A focused review.J. Indian Inst. Sci.2023103119120410.1007/s41745‑022‑00352‑7
     [Google Scholar]
  18. AbdelhafizA.H. Rodríguez-MañasL. MorleyJ.E. SinclairA.J. Hypoglycemia in older people - A less well recognized risk factor for frailty.Aging Dis.20156215616710.14336/AD.2014.033025821643
     [Google Scholar]
  19. Baeza-TrinidadR. Mosquera-LozanoJ.D. Safety of SGLT2 inhibitors in very elderly diabetic Type 2 patients in real life.Iberoam. J. Med.20235311812210.53986/ibjm.2023.0023
     [Google Scholar]
  20. LunatiM.E. CiminoV. GandolfiA. TrevisanM. MontefuscoL. PastoreI. PaceC. BetellaN. FavacchioG. BulgheroniM. BucciarelliL. MassariG. MascardiC. GirelliA. MorpurgoP.S. FolliF. LuziL. MiraniM. PintaudiB. BertuzziF. BerraC. FiorinaP. SGLT2-inhibitors are effective and safe in the elderly: The SOLD study.Pharmacol. Res.202218310639610.1016/j.phrs.2022.10639635970329
     [Google Scholar]
  21. Guzmán-CarrerasA. Vellisca-GonzálezA.M. Molina-PuenteJ.I. García-AlonsoR. Paz-CabezasM. Sánchez-SauceB. Aguilar-RodríguezF. Iguarán-BermúdezM.D.R. AndrèsE. Lorenzo-VillalbaN. Méndez-BailónM. Sodium-glucose cotransporter Type 2 inhibitors use in elderly polypathological patients with acute heart failure: PROFUND-IC registry.J. Clin. Med.20241312348510.3390/jcm1312348538930015
     [Google Scholar]
  22. CaricoI NOTA AIFA 100-Prescrizione degli inibitori del SGLT2, degli agonisti recettoriali del GLP1, degli inibitori del DPP4 e loro associazioni nel trattamento del diabete mellito tipo 2.2022Available from: https://www.quotidianosanita.it/allegati/allegato6341242.pdf
  23. ElSayedN.A. AleppoG. ArodaV.R. BannuruR.R. BrownF.M. BruemmerD. CollinsB.S. CusiK. DasS.R. GibbonsC.H. GiuriniJ.M. HilliardM.E. IsaacsD. JohnsonE.L. KahanS. KhuntiK. KosiborodM. LeonJ. LyonsS.K. MurdockL. PerryM.L. PrahaladP. PratleyR.E. SeleyJ.J. StantonR.C. SunJ.K. WoodwardC.C. Young-HymanD. GabbayR.A. on behalf of the American Diabetes Association Introduction and methodology: Standards of care in diabetes-2023.Diabetes Care202346Suppl. 1S1S410.2337/dc23‑Sint36507647
     [Google Scholar]
  24. PilottoA. FerrucciL. FranceschiM. D’AmbrosioL.P. ScarcelliC. CascavillaL. ParisF. PlacentinoG. SeripaD. DallapiccolaB. LeandroG. Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.Rejuvenation Res.200811115116110.1089/rej.2007.056918173367
     [Google Scholar]
  25. PilottoA. CustoderoC. MaggiS. PolidoriM.C. VeroneseN. FerrucciL. A multidimensional approach to frailty in older people.Ageing Res. Rev.20206010104710.1016/j.arr.2020.10104732171786
     [Google Scholar]
  26. ScheenA.J. Beneficial effects of SGLT2 inhibitors on fatty liver in Type 2 diabetes: A common comorbidity associated with severe complications.Diabetes Metab.201945321322310.1016/j.diabet.2019.01.00830708071
     [Google Scholar]
  27. JasleenB. VishalG.K. SameeraM. FahadM. BrendanO.B. DeionS. PemminatiS. Sodium-glucose cotransporter 2 (SGLT2) inhibitors: Benefits versus risk.Cureus2023151e3393910.7759/cureus.3393936819350
     [Google Scholar]
  28. ChenX. WangJ. LinY. YaoK. XieY. ZhouT. Cardiovascular outcomes and safety of SGLT2 inhibitors in chronic kidney disease patients.Front. Endocrinol.202314123640410.3389/fendo.2023.123640438047108
     [Google Scholar]
  29. FatimaA. RasoolS. DeviS. TalhaM. WaqarF. NasirM. KhanM.R. Ibne Ali JaffariS.M. HaiderA. ShahS.U. SapnaF.N.U. VarrassiG. KhatriM. KumarS. MohamadT. Exploring the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors: Expanding horizons beyond diabetes management.Cureus2023159e4624310.7759/cureus.4624337908957
     [Google Scholar]
  30. ShaoS.C. KuoL.T. ChienR.N. HungM.J. LaiE.C.C. SGLT2 inhibitors in patients with Type 2 diabetes with non-alcoholic fatty liver diseases: An umbrella review of systematic reviews.BMJ Open Diabetes Res. Care202082e00195610.1136/bmjdrc‑2020‑00195633268450
     [Google Scholar]
  31. ZhouP. TanY. HaoZ. XuW. ZhouX. YuJ. Effects of SGLT2 inhibitors on hepatic fibrosis and steatosis: A systematic review and meta-analysis.Front. Endocrinol.202314114483810.3389/fendo.2023.114483836936142
     [Google Scholar]
  32. PaddaI. MahtaniA. ParmarM. Sodium-glucose transport protein 2 (SGLT2) inhibitors.StatPearls.Treasure Island, FLStatPearls Publishing2024
     [Google Scholar]
  33. MasudaT. MutoS. FukudaK. WatanabeM. OharaK. KoepsellH. VallonV. NagataD. Osmotic diuresis by SGLT2 inhibition stimulates vasopressin-induced water reabsorption to maintain body fluid volume.Physiol. Rep.202082e1436010.14814/phy2.1436031994353
     [Google Scholar]
  34. SchönbergerE. MihaljevićV. SteinerK. ŠarićS. KurevijaT. MajnarićL.T. Bilić ĆurčićI. Canecki-VaržićS. Immunomodulatory effects of SGLT2 inhibitors—targeting inflammation and oxidative stress in aging.Int. J. Environ. Res. Public Health20232017667110.3390/ijerph2017667137681811
     [Google Scholar]
  35. ChiltonR. TikkanenI. CannonC.P. CroweS. WoerleH.J. BroedlU.C. JohansenO.E. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with Type 2 diabetes.Diabetes Obes. Metab.201517121180119310.1111/dom.1257226343814
     [Google Scholar]
  36. LiH. ShinS.E. SeoM.S. AnJ.R. ChoiI.W. JungW.K. FirthA.L. LeeD.S. YimM.J. ChoiG. LeeJ.M. NaS.H. ParkW.S. The anti-diabetic drug dapagliflozin induces vasodilation via activation of PKG and Kv channels.Life Sci.2018197465510.1016/j.lfs.2018.01.03229409796
     [Google Scholar]
  37. ErdemS. TitusA. PatelD. PatelN.N. SattarY. GlazierJ. AlraiesC.M. Sodium-glucose cotransporter 2 inhibitors: A scoping review of the positive implications on cardiovascular and renal health and dynamics for clinical practice.Cureus2023154e3731010.7759/cureus.3731037182087
     [Google Scholar]
  38. JanuzziJ.L.Jr ButlerJ. JarolimP. SattarN. VijapurkarU. DesaiM. DaviesM.J. Effects of canagliflozin on cardiovascular biomarkers in older adults with Type 2 diabetes.J. Am. Coll. Cardiol.201770670471210.1016/j.jacc.2017.06.01628619659
     [Google Scholar]
  39. BellaryS. BarnettA.H. SGLT2 inhibitors in older adults: Overcoming the age barrier.Lancet Healthy Longev.202344e127e12810.1016/S2666‑7568(23)00039‑937003269
     [Google Scholar]
  40. ScheenA.J. BonnetF. Efficacy and safety profile of SGLT2 inhibitors in the elderly: How is the benefit/risk balance?Diabetes Metab.202349210141910.1016/j.diabet.2023.10141936640828
     [Google Scholar]
  41. AldafasR. CrabtreeT. AlkharaijiM. VinogradovaY. IdrisI. Sodium-glucose cotransporter-2 inhibitors (SGLT2) in frail or older people with Type 2 diabetes and heart failure: A systematic review and meta-analysis.Age Ageing2024531afad25410.1093/ageing/afad25438287703
     [Google Scholar]
  42. MoneP. VarzidehF. JankauskasS.S. PansiniA. LombardiA. FrulloneS. SantulliG. SGLT2 inhibition via empagliflozin improves endothelial function and reduces mitochondrial oxidative stress: Insights from frail hypertensive and diabetic patients.Hypertension20227981633164310.1161/HYPERTENSIONAHA.122.1958635703100
     [Google Scholar]
  43. VartP ButtJH JongsN SchechterM ChertowGM WheelerDC Efficacy and safety of dapagliflozin in patients with chronic kidney disease across the spectrum of frailty.J. Gerontol. A.2024792glad18110.1093/gerona/glad181
     [Google Scholar]
  44. Cruz-JentoftA.J. BaeyensJ.P. BauerJ.M. BoirieY. CederholmT. LandiF. MartinF.C. MichelJ.P. RollandY. SchneiderS.M. TopinkováE. VandewoudeM. ZamboniM. European Working Group on Sarcopenia in Older People Sarcopenia: European consensus on definition and diagnosis.Age Ageing201039441242310.1093/ageing/afq03420392703
     [Google Scholar]
  45. AtiénzarP. AbizandaP. GuppyA. SinclairA.J. Diabetes and frailty: An emerging issue. Part 2: Linking factors.Br. J. Diabetes Vasc. Dis.201212311912210.1177/1474651412450304
     [Google Scholar]
  46. MorleyJ.E. Diabetes, sarcopenia, and frailty.Clin. Geriatr. Med.2008243455469, vi10.1016/j.cger.2008.03.00418672182
     [Google Scholar]
  47. MorleyJ.E. KimM.J. HarenM.T. Frailty and hormones.Rev. Endocr. Metab. Disord.20056210110810.1007/s11154‑005‑6722‑915843881
     [Google Scholar]
  48. KalyaniR.R. CorriereM. FerrucciL. Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases.Lancet Diabetes Endocrinol.201421081982910.1016/S2213‑8587(14)70034‑824731660
     [Google Scholar]
  49. KimJ. WeiY. SowersJ.R. Role of mitochondrial dysfunction in insulin resistance.Circ. Res.2008102440141410.1161/CIRCRESAHA.107.16547218309108
     [Google Scholar]
  50. MalikM.E. ButtJ.H. StrangeJ.E. FalkentoftA.C. JensenJ. AnderssonC. ZahirD. FosbølE. PetrieM.C. SattarN. McMurrayJ.J.V. KøberL. SchouM. Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with Type 2 diabetes and cardiovascular disease in Denmark: A cross-sectional, nationwide study.Lancet Healthy Longev.2023410e552e56010.1016/S2666‑7568(23)00164‑237734395
     [Google Scholar]
  51. NgN.M. NgY.S. ChuT.K. LauP. Factors affecting prescription of sodium-glucose co-transporter 2 inhibitors in patients with Type 2 diabetes mellitus with established cardiovascular disease/chronic kidney disease in Hong Kong: A qualitative study.BMC Prim. Care202223131710.1186/s12875‑022‑01928‑z36476327
     [Google Scholar]
  52. KehoeR. WuS.Y. LeskeM.C. ChylackL.T.Jr Comparing self-reported and physician-reported medical history.Am. J. Epidemiol.1994139881381810.1093/oxfordjournals.aje.a1170788178794
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128347041241129055001
Loading
Use of SGLT2 Inhibitors in Frail Older Adults is Associated with Increased Survival: A Retrospective Study
Curr. Pharm. Des. 31, 1290 (2025); https://doi.org/10.2174/0113816128347041241129055001
/content/journals/cpd/10.2174/0113816128347041241129055001
/content/journals/cpd/10.2174/0113816128347041241129055001
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): aging; Diabetes; multidimensional frailty; SGLT2 inhibitors; sodium-glucose co-transporter 2 inhibitors, multidimensional prognostic index (MPI)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test