[en] INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) are two major complications of type 2 diabetes (T2DM). Cardiovascular protection is a key objective, yet not fully reached in clinical practice. AREAS COVERED: Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven their efficacy in reducing major cardiovascular events in high-risk patients with T2DM and SGLT2is in reducing hospitalization for HF in placebo-controlled randomized trials. However, real-life studies worldwide revealed that only a minority of patients with T2DM receive either a GLP-1RA or an SGLT2i and surprisingly even less patients with established ASCVD or HF are treated with these cardioprotective antihyperglycemic agents. EXPERT OPINION: Bridging the gap between evidence-based cardiovascular protection with GLP-1RAs and SGLT2is and their underuse in daily clinical practice in patients with T2DM at high risk is crucial from a public health viewpoint. However, the task appears hazardous and the goal not attained considering the current failure. Education of specialists/primary care physicians and patients is critical. Multifaceted and coordinated interventions involving all actors (physicians, patients and broadly health-care system) must be implemented to stimulate the adoption of these cardioprotective antihyperglycemic medications as part of routine cardiovascular care among patients with T2DM.
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Bibliography
Joseph JJ, Deedwania P, Acharya T, et al. Comprehensive management of cardiovascular risk factors for adults with type 2 diabetes: a scientific statement from the American heart Association. Circulation. 2022; 145 (9): e722–e59. doi: 10.1161/CIR.0000000000001040
Cefalu WT, Kaul S, Gerstein HC, et al. Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors’ Expert Forum. Dia Care. 2018; 41 (1): 14–31. doi: 10.2337/dci17-0057
Ghosh-Swaby OR, Goodman SG, Leiter LA, et al. Glucose-lowering drugs or strategies, atherosclerotic cardiovascular events, and heart failure in people with or at risk of type 2 diabetes: an updated systematic review and meta-analysis of randomised cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2020; 8 (5): 418–435. doi: 10.1016/S2213-8587(20)30038-3
Wright AK, Carr MJ, Kontopantelis E, et al. Primary prevention of cardiovascular and heart failure events with SGLT2 inhibitors, GLP-1 receptor agonists, and their combination in type 2 diabetes. Diabetes Care. 2022; 45 (4): 909–918. doi: 10.2337/dc21-1113
Scheen AJ. Clinical pharmacology of antidiabetic drugs: what can be expected of their use? Presse Med. 2022; 52 (1): 104158. doi: 10.1016/j.lpm.2022.104158
Das SR, Everett BM, Birtcher KK, et al. Expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020; 76 (9): 1117–1145. doi: 10.1016/j.jacc.2020.05.037
Brown E, Heerspink HJL, Cuthbertson DJ, et al. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet. 2021; 398 (10296): 262–276. doi: 10.1016/S0140-6736(21)00536-5
Marx N, Davies MJ, Grant PJ, et al. Guideline recommendations and the positioning of newer drugs in type 2 diabetes care. Lancet Diabetes Endocrinol. 2021; 9 (1): 46–52. doi: 10.1016/S2213-8587(20)30343-0
Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American diabetes Association (ADA) and the European Association for the study of diabetes (EASD). Diabetologia. 2022; 65 (12): 1925–1966. doi: 10.1007/s00125-022-05787-2
Samson SL, Vellanki P, Blonde L, et al. American Association of clinical Endocrinology consensus statement: comprehensive type 2 diabetes management algorithm–2023 update. Endocr Pract. 2023; 29 (5): 305–340. doi: 10.1016/j.eprac.2023.02.001
Lim CE, Pasternak B, Eliasson B, et al. Use of sodium–glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists according to the 2019 ESC guidelines and the 2019 ADA/EASD consensus report in a national population of patients with type 2 diabetes. Eur J Prevent Cardiol. 2023; 30 (8): 634–643. doi: 10.1093/eurjpc/zwac315
McCoy RG, Van Houten HK, Karaca-Mandic P, et al. Second-line therapy for type 2 diabetes management: the treatment/benefit paradox of cardiovascular and kidney comorbidities. Diabetes Care. 2021; 44: 2302–2311. doi: 10.2337/dc20-2977
Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021; 9 (10): 653–662. doi: 10.1016/S2213-8587(21)00203-5
Giugliano D, Longo M, Signoriello S, et al. The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs. Cardiovasc Diabetol. 2022; 21 (1): 42. doi: 10.1186/s12933-022-01474-z
Marx N, Husain M, Lehrke M, et al. GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation. 2022; 146 (24): 1882–1894. doi: 10.1161/CIRCULATIONAHA.122.059595
Wu Q, Li D, Huang C, et al. Glucose control independent mechanisms involved in the cardiovascular benefits of glucagon-like peptide-1 receptor agonists. Biomed Pharmacother. 2022; 153: 113517. doi: 10.1016/j.biopha.2022.113517
Marx N, Federici M, Schütt K, et al.; ESC Scientific Document Group. ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023 Aug; 25: ehad192. doi: 10.1093/eurheartj/ehad192.
Rahman A, Alqaisi S, Saith SE, et al. The impact of glucagon-like peptide-1 receptor agonist on the cardiovascular outcomes in patients with type 2 diabetes mellitus: a meta-analysis and systematic review. Cardiol Res. 2023; 14 (4): 250–260. doi: 10.14740/cr1523
Mahtta D, Ramsey DJ, Lee MT, et al. Utilization rates of SGLT2 inhibitors and GLP-1 receptor agonists and their facility-level variation among patients with atherosclerotic cardiovascular disease and type 2 diabetes: insights from the department of Veterans Affairs. Diabetes Care. 2022; 45 (2): 372–380. doi: 10.2337/dc21-1815
Devineni D, Akbarpour M, Gong Y, et al. Inadequate use of newer treatments and glycemic control by cardiovascular risk and sociodemographic groups in US adults with diabetes in the NIH Precision Medicine Initiative all of Us Research Program. Cardiovasc Drugs Ther. 2022 Nov 15; published on line. doi: 10.1007/s10557-022-07403-2
Hao R, Myroniuk T, McGuckin T, et al. Underuse of cardiorenal protective agents in high-risk diabetes patients in primary care: a cross-sectional study. BMC Prim Care. 2022; 23 (1): 124. doi: 10.1186/s12875-022-01731-w
Honigberg MC, Chang LS, McGuire DK, et al. Use of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and cardiovascular disease: a review. JAMA Cardiol. 2020; 5 (10): 1182–1190. doi: 10.1001/jamacardio.2020.1966
Zheng C, Lin M, Chen Y, et al. Effects of sodium-glucose cotransporter type 2 inhibitors on cardiovascular, renal, and safety outcomes in patients with cardiovascular disease: a meta-analysis of randomized controlled trials. Cardiovasc Diabetol. 2021; 20 (1): 83. doi: 10.1186/s12933-021-01272-z
Gager GM, Gelbenegger G, Jilma B, et al. Cardiovascular outcome in patients treated with SGLT2 inhibitors for heart failure: a meta-analysis. Front Cardiovasc Med. 2021; 8: 691907. doi: 10.3389/fcvm.2021.691907
Inzucchi SE, Kosiborod M, Fitchett D, et al. Improvement in cardiovascular outcomes with empagliflozin is independent of glycemic control. Circulation. 2018; 138 (17): 1904–1907. doi: 10.1161/CIRCULATIONAHA.118.035759
Li CX, Liang S, Gao L, et al. Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: a real-world systematic review and meta-analysis. PLoS One. 2021; 16 (2): e0244689. doi: 10.1371/journal.pone.0244689
Hinton W, Ansari AS, Whyte MB, et al. Sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: are clinical trial benefits for heart failure reflected in real-world clinical practice? A systematic review and meta-analysis of observational studies. Diab Obes Metab. 2023; 25 (2): 501–515. doi: 10.1111/dom.14893
Hussain A, Ramsey D, Lee M, et al. Utilization rates of SGLT2 inhibitors among patients with type 2 diabetes, heart failure, and atherosclerotic cardiovascular disease: insights from the department of Veterans Affairs. JACC Heart Fail. 2023; 11 (8): 933–942. doi: 10.1016/j.jchf.2023.03.024
Ozaki AF, Ko DT, Chong A, et al. Prescribing patterns and factors associated with sodium–glucose cotransporter-2 inhibitor prescribing in patients with diabetes mellitus and atherosclerotic cardiovascular disease. CMAJ Open. 2023; 11 (3): E494–E503. doi: 10.9778/cmajo.20220039
Nargesi AA, Jeyashanmugaraja GP, Desai N, et al. Contemporary national patterns of eligibility and use of novel cardioprotective antihyperglycemic agents in type 2 diabetes mellitus. J Am Heart Assoc. 2021; 10 (13): e021084. doi: 10.1161/JAHA.121.021084
Nelson AJ, Ardissino M, Haynes K, et al. Gaps in evidence-based therapy use in insured patients in the United States with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. J Am Heart Assoc. 2021; 10 (2): e016835. doi: 10.1161/JAHA.120.016835
Nelson AJ, O’Brien EC, Kaltenbach LA, et al. Use of lipid-, blood pressure–, and glucose-lowering pharmacotherapy in patients with type 2 diabetes and atherosclerotic cardiovascular disease. JAMA Netw Open. 2022; 5 (2): e2148030. doi: 10.1001/jamanetworkopen.2021.48030
Zhai MZ, Avorn J, Liu J, et al. Variations in use of diabetes drugs with cardiovascular benefits among medicaid patients. JAMA Netw Open. 2022; 5: e2240117. doi: 10.1001/jamanetworkopen.2022.40117
Eberly LA, Yang L, Essien UR, et al. Racial, ethnic, and socioeconomic inequities in glucagon-like peptide-1 receptor agonist use among patients with diabetes in the US. JAMA Health Forum. 2021; 2 (12): e214182. doi: 10.1001/jamahealthforum.2021.4182
Khunti K, Jabbour S, Cos X, et al. Sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes: barriers and solutions for improving uptake in routine clinical practice. Diab Obes Metab. 2022; 24 (7): 1187–1196. doi: 10.1111/dom.14684
Bidulka P, Mathur R, Lugo-Palacios DG, et al. Ethnic and socioeconomic disparities in initiation of second-line antidiabetic treatment for people with type 2 diabetes in England: a cross-sectional study. Diab Obes Metab. 2023; 25 (1): 282–292. doi: 10.1111/dom.14874
Falkentoft AC, Andersen J, Malik ME, et al. Impact of socioeconomic position on initiation of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes - a Danish nationwide observational study. Lancet Reg Health Eur. 2022; 14: 100308. doi: 10.1016/j.lanepe.2022.100308
Karagiannis T, Bekiari E, Tsapas A. Socioeconomic aspects of incretin-based therapy. Diabetologia. 2023; 66 (10): 1859–1868. doi: 10.1007/s00125-023-05962-z
Arnold SV, Tang F, Cooper A, et al. Global use of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes Results from discover. BMC Endocr Disord. 2022; 22 (1): 111. doi: 10.1186/s12902-022-01026-2
Hanna J, Nargesi AA, Essien UR, et al. County-level variation in cardioprotective antihyperglycemic prescribing among medicare beneficiaries. Am J Prev Cardiol. 2022; 11: 100370. doi: 10.1016/j.ajpc.2022.100370
Nelson AJ, Pagidipati NJ, Aroda VR, et al. Incorporating SGLT2i and GLP-1RA for cardiovascular and kidney disease risk reduction: call for action to the cardiology community. Circulation. 2021; 144 (1): 74–84. doi: 10.1161/CIRCULATIONAHA.121.053766
Scheen AJ. Underuse of glucose-lowering medications associated with cardiorenal protection in type 2 diabetes: from delayed initiation to untimely discontinuation. Lancet Reg Health Eur. 2023; 29: 100627.
Chew BH, Mohd-Yusof BN, Lai PSM, et al. Overcoming therapeutic inertia as the achilles’ heel for improving suboptimal diabetes care: an integrative review. Endocrinol Metab. 2023; 38 (1): 34–42. doi: 10.3803/EnM.2022.1649
Schernthaner G, Shehadeh N, Ametov AS, et al. Worldwide inertia to the use of cardiorenal protective glucose-lowering drugs (SGLT2i and GLP-1 RA) in high-risk patients with type 2 diabetes. Cardiovasc Diabetol. 2020; 19: 185. doi: 10.1186/s12933-020-01154-w
Scheen AJ. Cardiovascular and renal protection with sodium-glucose cotransporter type 2 inhibitors: new paradigm in type 2 diabetes management…and potentially beyond. Ann Transl Med. 2019; 7: S132. doi: 10.21037/atm.2019.05.82
Davies MJ, Drexel H, Jornayvaz FR, et al. Cardiovascular outcomes trials: a paradigm shift in the current management of type 2 diabetes. Cardiovasc Diabetol. 2022; 21 (1): 144. doi: 10.1186/s12933-022-01575-9
Jacob S, Krentz AJ, Deanfield J, et al. Evolution of type 2 diabetes management from a glucocentric approach to cardio-renal risk reduction: the new paradigm of care. Drugs. 2021; 81 (12): 1373–1379. doi: 10.1007/s40265-021-01554-6
Gao Y, Peterson E, Pagidipati N. Barriers to prescribing glucose-lowering therapies with cardiometabolic benefits. Am Heart J. 2020; 224: 47–53. doi: 10.1016/j.ahj.2020.03.017
Pagidipati NJ, Nelson AJ, Kaltenbach LA, et al. Coordinated care to optimize cardiovascular preventive therapies in type 2 diabetes: a randomized clinical trial. JAMA. 2023; 329 (15): 1261–1270. doi: 10.1001/jama.2023.2854
Malik ME, Falkentoft AC, Jensen J, et al. Discontinuation and reinitiation of SGLT-2 inhibitors and GLP-1R agonists in patients with type 2 diabetes: a nationwide study from 2013 to 2021. Lancet Reg Health Eur. 2023; 29: 100617. doi: 10.1016/j.lanepe.2023.100617
Mustafa OG, Whyte MB. The use of GLP-1 receptor agonists in hospitalised patients: an untapped potential. Diabetes Metab Res Rev. 2019; 35: e3191. doi: 10.1002/dmrr.3191
Demidowich AP, Batty K, Zilbermint M. Instituting a successful discharge plan for patients with type 2 diabetes: challenges and solutions. Diabetes Spectr. 2022; 35 (4): 440–451. doi: 10.2337/dsi22-0013
Pierce JB, Vaduganathan M, Fonarow GC, et al. Contemporary use of sodium-glucose cotransporter-2 inhibitor therapy among patients hospitalized for heart failure with reduced ejection fraction in the US: the get with the guidelines-heart failure registry. JAMA Cardiol. 2023; 8 (7): 652–661. doi: 10.1001/jamacardio.2023.1266
Ferro EG, Pitt B, Bhatt DL. SGLT-2 inhibitors in heart failure: time for broader eligibility and earlier initiation. Cleve Clin J Med. 2021; 88 (11): 601–606. doi: 10.3949/ccjm.88a.21045
Norgard NB, Lopez-Candales A. The rise of SGLT2 inhibitors: the time is now for cardiovascular specialists to lead the charge. Postgrad Med. 2022; 134 (1): 11–13. doi: 10.1080/00325481.2021.2002580
Ofori-Asenso R, Sahle BW, Chin KL, et al. Poor adherence and persistence to sodium glucose co-transporter 2 inhibitors in real-world settings: evidence from a systematic review and meta-analysis. Diabetes Metab Res Rev. 2021; 37: e3350. doi: 10.1002/dmrr.3350
Alkabbani W, Shah BR, Zongo A, et al. Post-initiation predictors of discontinuation of the sodium-glucose cotransporter-2 inhibitors: a comparative cohort study from the United Kingdom. Diab Obes Metab. 2023. published on line. doi: 10.1111/dom.15241
Weiss T, Carr RD, Pal S, et al. Real-world adherence and discontinuation of glucagon-like peptide-1 receptor agonists therapy in type 2 diabetes mellitus patients in the United States. Patient Prefer Adherence. 2020; 14: 2337–2345. doi: 10.2147/PPA.S277676
Palanca A, Ampudia-Blasco FJ, Calderon JM, et al. Real-world evaluation of GLP-1 receptor agonist therapy persistence, adherence and therapeutic inertia among obese adults with type 2 diabetes. Diabetes Ther. 2023; 14 (4): 723–736. doi: 10.1007/s13300-023-01382-9
Lee DSU, Lee H. Adherence and persistence rates of major antidiabetic medications: a review. Diabetol Metab Syndr. 2022; 14 (1): 12. doi: 10.1186/s13098-022-00785-1
Sikirica MV, Martin AA, Wood R, et al. Reasons for discontinuation of GLP1 receptor agonists: data from a real-world cross-sectional survey of physicians and their patients with type 2 diabetes. Diabetes Metab Syndr Obes. 2017; 10: 403–412. doi: 10.2147/DMSO.S141235
Byrne J, Willis A, Dunkley A, et al. Individual, healthcare professional and system-level barriers and facilitators to initiation and adherence to injectable therapies for type 2 diabetes: a systematic review and meta-ethnography. Diabet Med. 2022; 39: e14678. doi: 10.1111/dme.14678
Dave CV, Schneeweiss S, Wexler DJ, et al. Trends in clinical characteristics and prescribing preferences for SGLT2 inhibitors and GLP-1 receptor agonists, 2013–2018. Diabetes Care. 2020; 43 (4): 921–924. doi: 10.2337/dc19-1943
Weeda ER, Muraoka AK, Brock MD, et al. Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: a meta-analysis. Int J Clin Pract. 2021; 75: e14060. doi: 10.1111/ijcp.14060
Isaacs DM, Kruger DF, Spollett GR. Optimizing therapeutic outcomes with oral semaglutide: a patient-centered approach. Diabetes Spectr. 2021; 34 (1): 7–19. doi: 10.2337/ds20-0016
Luo J, Feldman R, Callaway Kim K, et al. Evaluation of out-of-pocket costs and treatment intensification with an SGLT2 inhibitor or GLP-1 RA in patients with type 2 diabetes and cardiovascular disease. JAMA Netw Open. 2023; 6 (6): e2317886. doi: 10.1001/jamanetworkopen.2023.17886
Essien UR, Singh B, Swabe G, et al. Association of prescription co-payment with adherence to glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor therapies in patients with heart failure and diabetes. JAMA Netw Open. 2023; 6: e2316290. doi: 10.1001/jamanetworkopen.2023.16290
Consoli A, Formoso G. Potential side effects to GLP-1 agonists: understanding their safety and tolerability. Expert Opin Drug Saf. 2015; 14 (2): 207–218. doi: 10.1517/14740338.2015.987122
Scheen AJ. An update on the safety of SGLT2 inhibitors. Expert Opin Drug Safety. 2019; 18 (4): 295–311. doi: 10.1080/14740338.2019.1602116
Hong D, Si L, Jiang M, et al. Cost effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors: a systematic review. PharmacoEconomics. 2019; 37 (12): 777–818. doi: 10.1007/s40273-019-00833-1
McEwan P, Bennett H, Khunti K, et al. Assessing the cost-effectiveness of sodium–glucose cotransporter-2 inhibitors in type 2 diabetes mellitus: a comprehensive economic evaluation using clinical trial and real-world evidence. Diab Obes Metab. 2020; 22 (12): 2364–2374. doi: 10.1111/dom.14162
Morton JI, Marquina C, Shaw JE, et al. Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis. Diabetologia. 2023; 66 (4): 642–656. doi: 10.1007/s00125-022-05832-0
Ferrannini E, Rosenstock J. Clinical translation of cardiovascular outcome trials in type 2 diabetes: is there more or is there less than meets the eye? Diabetes Care. 2021; 44 (3): 641–646. doi: 10.2337/dc20-0913
Scheen AJ. Series: implications of the recent CVOTs in type 2 diabetes: impact on guidelines: the endocrinologist point of view. Diabet Res Clin Pract. 2020; 159: 107726. doi: 10.1016/j.diabres.2019.05.005
Rasalam R, Abdo S, Deed G, et al. Early type 2 diabetes treatment intensification with glucagon-like peptide-1 receptor agonists in primary care: an Australian perspective on guidelines and the global evidence. Diab Obes Metab. 2023; 25 (4): 901–915. doi: 10.1111/dom.14953
McEwan P, Foos V, Martin B, et al. Estimating the value of sodium-glucose cotransporter-2 inhibitors within the context of contemporary guidelines and the totality of evidence. Diab Obes Metab. 2023; 25 (7): 1830–1838. doi: 10.1111/dom.15040
Sandhu AT, Cohen DJ. Cost-effectiveness of sodium-glucose cotransporter-2 inhibitors for patients with heart failure and preserved ejection fraction—living on the edge. JAMA Cardiol. 2023; 8 (5): 415–416. doi: 10.1001/jamacardio.2023.0087
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