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Pharmacological treatment of type 2 diabetes in elderly patients with heart failure: randomized trials and beyond

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Abstract

Heart failure (HF) and type 2 diabetes mellitus (T2DM) represent two important public health problems, and despite improvements in the management of both diseases, they are responsible for high rates of hospitalizations and mortality. T2DM accelerates physiological cardiac aging through hyperglycemia and hyperinsulinemia. Thus, HF and T2DM are chronic diseases widely represented in elderly people who often are affected by numerous comorbidities with important functional limitations making it difficult to apply the current guidelines. Several antidiabetic drugs should be used with caution in elderly individuals with T2DM. For instance, sulfonylureas should be avoided due to the risk of hypoglycemia associated with its use. Insulin should be used with caution because it is associated with higher risk of hypoglycemia, and may determine fluid retention which can lead to worsening of HF. Thiazolindinediones should be avoided due to the increased risk of fluid retention and HF. Biguanides may lead to a slightly increased risk of lactic acidosis in particular in elderly individuals with impaired renal function. Dipeptidyl peptidase 4 (DPP-4) inhibitors are safe having few side effects, minimal risk of hypoglycemia, and a neutral effect on cardiovascular (CV) outcome, even if it has been reported that saxagliptin treatment is associated with increased risk of hospitalizations for HF (hHF). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a CV protection without a significant reduction in hHF. On the other hand, sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown a significant improvement in CV outcome, with a strong reduction of hHF and a positive impact on renal damage progression. However, it is necessary to consider the possible some side effects related to their use in elderly individuals including hypotension, bone fractures, and ketoacidosis.

It is important to remark that elderly patients, in particular the very elderly, are not sufficiently represented in the trials; thus, the management and treatment of elderly diabetic patients with HF should be mainly based on the integration of scientific evidence with clinical judgment and patients’ condition, with respect to the dignity and quality of life.

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References

  1. James SL, Abate D, Abate KH, et al (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. https://doi.org/10.1016/S0140-6736(18)32279-7

  2. Groenewegen A, Rutten FH, Mosterd A, Hoes AW (2020) Epidemiology of heart failure. Eur J Heart Fail. https://doi.org/10.1002/ejhf.1858

    Article  PubMed  Google Scholar 

  3. van Riet EE, Hoes AW, Wagenaar KP, et al (2016) Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail.https://scite.ai/reports/10.1002/ejhf.483.

  4. Guariguata L, Whiting DR, Hambleton I et al (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. https://doi.org/10.1016/j.diabres.2013.11.002

    Article  PubMed  Google Scholar 

  5. Dunlay SM, Givertz MM, Aguilar D et al (2019) Type 2 diabetes mellitus and heart failure: a scientific statement from the american heart association and the heart failure society of america: this statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. https://doi.org/10.1161/CIR.0000000000000691

    Article  PubMed  Google Scholar 

  6. van Melle JP, Bot M, de Jonge P et al (2010) Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease: data from the heart and soul study. Diabetes Care. https://doi.org/10.2337/dc10-0286

    Article  PubMed  PubMed Central  Google Scholar 

  7. Matsushita K, Blecker S, Pazin-Filho A et al (2010) The association of hemoglobin A1c with incident heart failure among people without diabetes: the atherosclerosis risk in communities study. Diabetes. https://doi.org/10.2337/db10-0165

    Article  PubMed  PubMed Central  Google Scholar 

  8. Swoboda PP, McDiarmid AK, Erhayiem B et al (2017) Diabetes mellitus, microalbuminuria, and subclinical cardiac disease: identification and monitoring of individuals at risk of heart failure. J Am Heart Assoc. https://doi.org/10.1161/JAHA.117.005539

  9. Preiss D, van Veldhuisen DJ, Sattar N et al (2012) Eplerenone and new-onset diabetes in patients with mild heart failure: results from the eplerenone in mild patients hospitalization and survival study in heart failure (EMPHASIS-HF). Eur J Heart Fail. https://doi.org/10.1093/eurjhf/hfs067

  10. Paolillo S, Rengo G, Pellegrino T et al (2015) Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure. Eur Heart J Cardiovasc Imaging. https://doi.org/10.1093/ehjci/jev061

    Article  PubMed  Google Scholar 

  11. Park JJ (2021) Epidemiology, pathophysiology, diagnosis and treatment of heart failure in diabetes. Diabetes Metab J. https://doi.org/10.4093/dmj.2020.0282

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rubler S, Dlugash J, Yuceoglu YZ et al (1972) New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. https://doi.org/10.1016/0002-9149(72)90595-4

    Article  PubMed  Google Scholar 

  13. Marwick TH, Ritchie R, Shaw JE, Kaye D (2018) Implications of underlying mechanisms for the recognition and management of diabetic cardiomyopathy. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2017.11.019

    Article  PubMed  Google Scholar 

  14. Petrie MC, Verma S, Docherty KF et al (2020) Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. https://doi.org/10.1001/jama.2020.1906

    Article  PubMed  PubMed Central  Google Scholar 

  15. Allen LA, Gheorghiade M, Reid KJ et al (2011) Identifying patients hospitalized with heart failure at risk for unfavorable future quality of life. Circ Cardiovasc Qual Outcomes. https://doi.org/10.1161/CIRCOUTCOMES.110.958009

    Article  PubMed  PubMed Central  Google Scholar 

  16. Targher G, Dauriz M, Laroche C et al (2017) In-hospital and 1-year mortality associated with diabetes in patients with acute heart failure: results from the ESC-HFA heart failure long-term registry. Eur J Heart Fail. https://doi.org/10.1002/ejhf.679

    Article  PubMed  Google Scholar 

  17. Dauriz M, Targher G, Laroche C et al (2017) Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA heart failure long-term registry. Diabetes Care. https://doi.org/10.2337/dc16-0574

    Article  PubMed  Google Scholar 

  18. MacDonald MR, Petrie MC, Varyani F et al 2008. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme. Eur Heart J. https://doi.org/10.1093/eurheartj/ehn153

  19. Kristensen SL, Mogensen UM, Jhund PS et al (2017) Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-PRESERVE trial (irbesartan in heart failure with preserved ejection fraction). Circulation. https://doi.org/10.1161/CIRCULATIONAHA.116.024593

    Article  PubMed  Google Scholar 

  20. Lawson CA, Jones PW, Teece L et al (2018) Association between type 2 diabetes and all-cause hospitalization and mortality in the UK general heart failure population: stratification by diabetic glycemic control and medication intensification. JACC Heart Fail. https://doi.org/10.1016/j.jchf.2017.08.020

    Article  PubMed  Google Scholar 

  21. Triposkiadis F, Xanthopoulos A, Butler J (2019) Cardiovascular aging and heart failure: JACC review topic of the week. J Am Coll Cardiol. 2019https://doi.org/10.1016/j.jacc.2019.06.053

  22. Hanon O, Belmin J, Benetos A et al (2021) Consensus of experts from the french society of geriatrics and gerontology on the management of heart failure in very old subjects. Arch Cardiovasc Dis. https://doi.org/10.1016/j.acvd.2020.12.001

    Article  PubMed  Google Scholar 

  23. Strain WD, Down S, Brown P et al (2021) Diabetes and frailty: an expert consensus statement on the management of older adults with type 2 diabetes. Diabetes Ther. https://doi.org/10.1007/s13300-021-01035-9

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kalra S, Sharma SK (2018) Diabetes in the elderly. Diabetes Ther. https://doi.org/10.1007/s13300-018-0380-x

    Article  PubMed  PubMed Central  Google Scholar 

  25. Parker SG, McLeod A, McCue P et al (2017) New horizons in comprehensive geriatric assessment. Age Ageing. https://doi.org/10.1093/ageing/afx104

    Article  PubMed  PubMed Central  Google Scholar 

  26. Clegg A, Young J, Iliffe S et al (2013) Frailty in elderly people. Lancet. https://doi.org/10.1016/S0140-6736(12)62167-9

    Article  PubMed  Google Scholar 

  27. Clegg A, Bates C, Young J et al (2016) Development and validation of an electronic frailty index using routine primary care electronic health record data. Age Ageing. https://doi.org/10.1093/ageing/afw039

  28. Pandey A, Kitzman D, Reeves G (2019) Frailty is intertwined with heart failure: mechanisms, prevalence, prognosis, assessment, and management. JACC Heart Fail. https://doi.org/10.1016/j.jchf.2019.10.005

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ponikowski P, Voors AA, Anker SD et al (2016) ESC scientific document group. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (ESC) developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J. https://doi.org/10.1093/eurheartj/ehw128

  30. Biessels GJ, Despa F (2018) Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. https://doi.org/10.1038/s41574-018-0048-7

    Article  PubMed  PubMed Central  Google Scholar 

  31. Trachanas K, Sideris S, Aggeli C et al (2014) Diabetic cardiomyopathy: from pathophysiology to treatment. Hell J Cardiol 55:411–421

    Google Scholar 

  32. Ahmed SS, Jafer GA, Narang RM et al (1975) Preclinical abnormality of left ventricular function in diabetes mellitus. Am Heart J. https://doi.org/10.1016/0002-8703(75)90039-3

    Article  PubMed  Google Scholar 

  33. Wang J, Song Y, Wang Q et al (2006) Causes and characteristics of diabetic cardiomyopathy. Rev Diabet Stud. https://doi.org/10.1900/RDS.2006.3.108

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kurt M, Wang J, Torre-Amione G et al (2009) Left atrial function in diastolic heart failure. Circ Cardiovasc Imaging. https://doi.org/10.1161/CIRCIMAGING.108.813071

    Article  PubMed  Google Scholar 

  35. Lamberts RR, Lingam SJ, Wang HY et al (2014) Impaired relaxation despite upregulated calcium-handling protein atrial myocardium from type 2 diabetic patients with preserved ejection fraction. Cardiovasc Diabetol. https://doi.org/10.1186/1475-2840-13-72

    Article  PubMed  PubMed Central  Google Scholar 

  36. Otake H, Suzuki H, Honda T, Maruyama Y (2009) Influences of autonomic nervous system on atrial arrhythmogenic substrates and the incidence of atrial fibrillation in diabetic heart. Int Heart J. https://doi.org/10.1536/ihj.50.627

    Article  PubMed  Google Scholar 

  37. Cameli M, Lisi M, Focardi M et al (2012) Left atrial deformation analysis by speckle tracking echocardiography for prediction of cardiovascular outcomes. Am J Cardiol. https://doi.org/10.1016/j.amjcard.2012.03.022

    Article  PubMed  Google Scholar 

  38. Liu JH, Chen Y, Yuen M et al (2016) Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. https://doi.org/10.1016/j.amjcard.2012.03.022

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tadic M, Cuspidi C, Vukomanovic V et al (2018) Layer-specific deformation of the left ventricle in uncomplicated patients with type 2 diabetes and arterial hypertension. Arch Cardiovasc Dis. https://doi.org/10.1016/j.acvd.2017.01.014

    Article  PubMed  Google Scholar 

  40. Abou R, Leung M, Khidir MJH et al (2017) Influence of aging on level and layer-specifc left ventricular longitudinal strain in subjects without structural heart disease. Am J Cardiol. https://doi.org/10.1016/j.amjcard.2017.08.027

    Article  PubMed  Google Scholar 

  41. Sciacqua A, Perticone M, Miceli S et al (2019) Elevated 1-h post-load plasma glucose is associated with right ventricular morphofunctional parameters in hypertensive patients. Endocrine 64. https://doi.org/10.1007/s12020-019-01873-5

  42. Lee YC, Chang CH, Dong YH et al (2017) Comparing the risks of hospitalized heart failure associated with glinide, sulfonylurea, and acarbose use in type 2 diabetes: a nationwide study. Int J Cardiol. https://doi.org/10.1016/j.ijcard.2016.11.022

    Article  PubMed  PubMed Central  Google Scholar 

  43. American Diabetes Association (2021) Older adults: standards of medical care in diabetes. Diabetes Care. https://doi.org/10.2337/dc21-S012

    Article  Google Scholar 

  44. LeRoith D, Jan Biessels G, Braithwaite SB et al (2019) Treatment of diabetes in older adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2019-00198

    Article  PubMed  PubMed Central  Google Scholar 

  45. American Geriatrics Society (2019) Updated AGS beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. https://doi.org/10.1111/jgs.15767

    Article  Google Scholar 

  46. Zoungas S, Patel A, Chalmers J et al (2010) Severe hypoglycemia and risks of vascular events and death. N Engl J Med. https://doi.org/10.1056/NEJMoa1003795

    Article  PubMed  Google Scholar 

  47. Dargie HJ, Hildebrandt PR, Riegger GA et al (2007) A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with new york heart association functional class I or II heart failure. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2006.10.077

    Article  PubMed  Google Scholar 

  48. Eurich DT, Weir DL, Majumdar SR et al (2013) Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail. https://doi.org/10.1161/CIRCHEARTFAILURE.112.000162

    Article  PubMed  Google Scholar 

  49. Pratley RE, Husain M, Lingvay I et al (2019) Heart failure with insulin degludec versus glargine U100 in patients with type 2 diabetes at high risk of cardiovascular disease: DEVOTE 14. Cardiovasc Diabetol. https://doi.org/10.1186/s12933-019-0960-8

    Article  PubMed  PubMed Central  Google Scholar 

  50. Gerstein HC, Bosch J, Dagenais GR et al (2012) Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. https://doi.org/10.1056/NEJMoa1203858

    Article  PubMed  Google Scholar 

  51. Cosmi F, Shen L, Magnoli M et al (2018) Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. Eur J Heart Fail. https://doi.org/10.1002/ejhf.1146

    Article  PubMed  Google Scholar 

  52. Dunlay SM, Givertz MM, Aguilar D et al (2019) Type 2 diabetes mellitus and heart failure: a scientific statement from the american heart association and the heart failure society of america: this statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. https://doi.org/10.1161/CIR.0000000000000691

    Article  PubMed  Google Scholar 

  53. Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. https://doi.org/10.1056/NEJMoa1307684

    Article  PubMed  Google Scholar 

  54. Leiter LA, Teoh H, Braunwald E et al (2015) Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care. https://doi.org/10.2337/dc14-2868

    Article  PubMed  PubMed Central  Google Scholar 

  55. Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa1501352

    Article  PubMed  PubMed Central  Google Scholar 

  56. Bethel MA, Engel SE, Green JB et al (2017) Assessing the safety of sitagliptin in older participants in the trial evaluating cardiovascular outcomes with sitagliptin (TECOS). Diabetes Care. https://doi.org/10.2337/dc16-1135

    Article  PubMed  Google Scholar 

  57. White WB, Cannon CP, Heller SR et al (2015) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa1305889

    Article  PubMed  PubMed Central  Google Scholar 

  58. Zannad F, Cannon CP, Cushman WC et al (2015) Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. https://doi.org/10.1016/S0140-6736(14)62225-X

    Article  PubMed  Google Scholar 

  59. Rosenstock J, Perkovic V, Johansen OE et al (2019) Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2018.18269

    Article  PubMed  PubMed Central  Google Scholar 

  60. Cooper ME, Rosenstock J, Kadowaki T et al (2020) Cardiovascular and kidney outcomes of linagliptin treatment in older people with type 2 diabetes and established cardiovascular disease and/or kidney disease: a prespecified subgroup analysis of the randomized, placebo-controlled CARMELINA trial. Diabetes Obes Metab. https://doi.org/10.1111/DOM.13995

    Article  PubMed  PubMed Central  Google Scholar 

  61. Rosenstock J, Kahn SE, Johansen OE et al (2019) Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2019.13772

    Article  PubMed  PubMed Central  Google Scholar 

  62. Espeland MA, Pratley RE, Rosenstock J et al (2021) Cardiovascular outcomes and safety with linagliptin, a dipeptidyl peptidase-4 inhibitor, compared with the sulphonylurea glimepiride in older people with type 2 diabetes: a subgroup analysis of the randomized CAROLINA trial. Diabetes Obes Metab.https://doi.org/10.1111/dom.14254

  63. Ledesma G, Umpierrez GE, Morley JE et al (2019) Efficacy and safety of linagliptin to improve glucose control in older people with type 2 diabetes on stable insulin therapy: a randomized trial. Diabetes Obes Metab. https://doi.org/10.1111/DOM.13829

    Article  PubMed  Google Scholar 

  64. Shen J, Greenberg BH (2021) Diabetes management in patients with heart failure. Diabetes Metab J. https://doi.org/10.4093/dmj.2020.0296

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zheng SL, Roddick AJ, Aghar-Jaffar R et al (2018) Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. https://doi.org/10.1001/jama.2018.3024

    Article  PubMed  PubMed Central  Google Scholar 

  66. Freeman J (2019) Management of hypoglycemia in older adults with type 2 diabetes. Postgrad Med. https://doi.org/10.1080/00325481.2019.1578590

    Article  PubMed  Google Scholar 

  67. Dave CV, Schneeweiss S, Wexler DJ et al (2020) Trends in clinical characteristics and prescribing preferences for SGLT2 inhibitors and GLP-1 receptor agonists, 2013–2018. Diabetes Care. https://doi.org/10.2337/dc19-1943

    Article  PubMed  PubMed Central  Google Scholar 

  68. Herrera Comoglio R, Vidal Guitart X (2020) Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs): a systematic review and meta-analysis of observational cohort studies. Int J Clin Pract. https://doi.org/10.1111/ijcp.13553

  69. North EJ, Newman JD (2019) Review of cardiovascular outcomes trials of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Curr Opin Cardiol. https://doi.org/10.1097/HCO.0000000000000673

    Article  PubMed  PubMed Central  Google Scholar 

  70. Marsico F, Paolillo S, Gargiulo P et al (2020) Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. Eur Heart J. https://doi.org/10.1093/eurheartj/ehaa082

    Article  PubMed  Google Scholar 

  71. Karagiannis T, Tsapas A, Athanasiadou E et al (2021) GLP-1 receptor agonists and SGLT2 inhibitors for older people with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract. https://doi.org/10.1016/j.diabres.2021.108737

    Article  PubMed  Google Scholar 

  72. Pfeffer MA, Claggett B, Diaz R et al (2015) Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. https://doi.org/10.1056/NEJMoa1509225

    Article  PubMed  Google Scholar 

  73. Marso SP, Daniels GH, Brown-Frandsen K et al (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa1603827

    Article  PubMed  PubMed Central  Google Scholar 

  74. Marso SP, Bain SC, Consoli A et al (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. https://www.nejm.org/doi/full/10.1056/NEJMoa1607141

  75. Holman RR, Bethel MA, Mentz RJ et al (2017) Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa161291

    Article  PubMed  PubMed Central  Google Scholar 

  76. Hernandez AF, Green JB, Janmohamed S et al (2018) Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (harmony outcomes): a double-blind, randomised placebo-controlled trial. Lancet. https://doi.org/10.1016/S0140-6736(18)32261-X

    Article  PubMed  Google Scholar 

  77. Gerstein HC, Colhoun HM, Dagenais GR et al (2019) Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. https://doi.org/10.1016/S0140-6736(19)31149-3

    Article  PubMed  Google Scholar 

  78. Margulies KB, Hernandez AF, Redfield MM et al (2016) NHLBI heart failure clinical research network. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA 316(5):500–508

  79. Longato E, Di Camillo B, Sparacino G et al (2020) Better cardiovascular outcomes of type 2 diabetic patients treated with GLP-1 receptor agonists versus DPP-4 inhibitors in clinical practice. Cardiovasc Diabetol. https://doi.org/10.1186/s12933-020-01049-w

    Article  PubMed  PubMed Central  Google Scholar 

  80. Longato E, Di Camillo B, Sparacino G et al (2020) Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life. BMJ Open Diabetes Res Care. https://doi.org/10.1136/bmjdrc-2020-001451

    Article  PubMed  PubMed Central  Google Scholar 

  81. Longato E, Di Camillo B, Sparacino G et al (2021) Cardiovascular effectiveness of human-based vs. exendin-based glucagon like peptide-1 receptor agonists: a retrospective study in patients with type 2 diabetes. Eur J Prev Cardiol.https://doi.org/10.1093/eurjpc/zwaa081

  82. Trevisan M, Fu EL, Szummer K et al (2021) Glucagon-like peptide-1 receptor agonists and the risk of cardiovascular events in diabetes patients surviving an acute myocardial infarction. Eur Heart J Cardiovasc Pharmacother. https://doi.org/10.1093/ehjcvp/pvaa004

    Article  PubMed  Google Scholar 

  83. Seferovic PM, Coats AJS, Ponikowski P et al (2020) European society of cardiology/heart failure association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail. https://doi.org/10.1002/ejhf.1673

    Article  PubMed  Google Scholar 

  84. Lytvyn Y, Bjornstad P, Udell JA, Lovshin JA, Cherney DZI (2017) Sodium glucose cotransporter-2 inhibition in heart failure. Circulation. https://doi.org/10.1161

  85. Butler J, Usman MS, Khan MS et al (2020) Efficacy and safety of SGLT2 inhibitors in heart failure: systematic review and meta-analysis. ESC Heart Failure. https://doi.org/10.1002/ehf2.13169

    Article  PubMed  PubMed Central  Google Scholar 

  86. Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa1504720

    Article  PubMed  Google Scholar 

  87. Neal B, Perkovic V, Mahaffey KW et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa1611925

    Article  PubMed  Google Scholar 

  88. Rådholm K, Figtree G, Perkovic V et al (2018) Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS program. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.118.034222

    Article  PubMed  PubMed Central  Google Scholar 

  89. Wiviott SD, Raz I, Bonaca MP et al (2019) Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa1812389

    Article  PubMed  Google Scholar 

  90. Cahn A, Mosenzon O, Wiviott SD et al (2020) Efficacy and safety of dapagliflozin in the elderly: analysis from the DECLARE–TIMI 58 study. Diabetes Care 2020. https://doi.org/10.2337/dc19-1476

  91. Cannon CP, Pratley R, Dagogo-Jack S et al (2020) Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa2004967

    Article  PubMed  Google Scholar 

  92. Cosentino F, Cannon CP, Cherney DZI et al (2020) Efficacy of ertugliflozin on heart failure–related events in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.120.050255

    Article  PubMed  PubMed Central  Google Scholar 

  93. Bhatt DL, Szarek M, Steg PG et al (2021) Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. https://doi.org/10.1056/NEJMoa2030183

    Article  PubMed  Google Scholar 

  94. Lam CSP, Karasik A, Melzer-Cohen C et al (2021) Association of sodium-glucose cotransporter-2 inhibitors with outcomes in type 2 diabetes with reduced and preserved left ventricular ejection fraction: analysis from the CVD-REAL 2 study. Diabetes Obes Metab. https://doi.org/10.1111/dom.14356

    Article  PubMed  PubMed Central  Google Scholar 

  95. McMurray JJV, Solomon SD, Inzucchi SE et al (2019) Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. https://doi.org/10.1056/NEJMoa1911303

    Article  PubMed  Google Scholar 

  96. Martinez FA, Serenelli M, Nicolau JC et al (2019) Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to age. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.119.044133

    Article  PubMed  PubMed Central  Google Scholar 

  97. Nassif ME, Qintar M, Windsor SL et al (2021) Empagliflozin effects on pulmonary artery pressure in patients with heart failure. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.120.052503

    Article  PubMed  Google Scholar 

  98. Packer M, Anker SD, Butler J et al (2020) Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. https://doi.org/10.1056/NEJMoa2022190

    Article  PubMed  Google Scholar 

  99. Zannad F, Ferreira JP, Pocock SJ et al (2020) SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-reduced and DAPA-HF trials. Lancet. https://doi.org/10.1016/S0140-6736(20)31824-9

    Article  PubMed  Google Scholar 

  100. Heerspink HJL, Perkins BA, Fitchett DH et al (2016) Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.116.021887

    Article  PubMed  Google Scholar 

  101. Kuchay MS, Krishan S, Mishra SK et al (2018) Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT trial). Diabetes Care. https://doi.org/10.2337/dc18-0165

    Article  PubMed  Google Scholar 

  102. Santos-Gallego CG, Requena-Ibanez JA, San Antonio R et al (2019) Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2019.01.056

    Article  PubMed  Google Scholar 

  103. Uthman L, Baartsceer A, Bleijlevens B et al (2018) Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia. https://doi.org/10.1007/s00125-017-4509-7

    Article  PubMed  Google Scholar 

  104. Seferović PM, Coats AJS, Ponikowski P et al (2020) European society of cardiology/heart failure association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail. https://doi.org/10.1002/ejhf.1673

    Article  PubMed  Google Scholar 

  105. Sesti G, Incalzi RA, Bonora E et al (2018) Management of diabetes in older adults. Nutr Metab Cardiovasc Dis. https://doi.org/10.1016/j.numecd.2017.11.007

    Article  PubMed  Google Scholar 

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Sciacqua, A., Succurro, E., Armentaro, G. et al. Pharmacological treatment of type 2 diabetes in elderly patients with heart failure: randomized trials and beyond. Heart Fail Rev 28, 667–681 (2023). https://doi.org/10.1007/s10741-021-10182-x

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