Cardiovascular outcome studies in type 2 diabetes: Comparison between SGLT2 inhibitors and GLP-1 receptor agonists.

[en] Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are two pharmacological classes that have proven their efficacy to reduce major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease in large prospective cardiovascular outcome trials (CVOTs): EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). Some heterogeneity appears to exist between the various agents within the two pharmacological classes. Whether these positive results could be extrapolated to patients without cardiovascular disease is still unknown. The underlying mechanisms remain a matter of debate but appear to differ between SGLT2is and GLP-1RAs. One crucial question is which patient's characteristics should be taken into account to guide the choice between a SGLT2i or a GLP-1RA according to a personalized approach. Heart failure should encourage the use of a SGLT2i whereas moderate to severe chronic kidney disease should favour the prescription of a GLP-1RA. Despite the results of recent CVOTs, numerous patients who are good candidates for benefiting of these agents do not receive them in clinical practice. Currently, there is a paradigm shift in T2DM management, moving from a primary objective of glucose control to a cardiovascular and renal protection.

Disciplines :

Cardiovascular & respiratory systems
Pharmacy, pharmacology & toxicology
Endocrinology, metabolism & nutrition

Author, co-author :

Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques

Language :

English

Title :

Cardiovascular outcome studies in type 2 diabetes: Comparison between SGLT2 inhibitors and GLP-1 receptor agonists.

Publication date :

2018

Journal title :

Diabetes Research and Clinical Practice

ISSN :

0168-8227

eISSN :

1872-8227

Publisher :

Elsevier, Amsterdam, Netherlands

Volume :

143

Pages :

88-100

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 17 August 2018

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Bibliography

American Diabetes Association, 9. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care 41:Suppl 1 (2018), S86–S104.
Ryden, L., Grant, P.J., Anker, S.D., Berne, C., Cosentino, F., Danchin, N., et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 34:39 (2013), 3035–3087.
Ceriello, A., Gavin, J. 3rd, Boulton, A.J.M., Blickstead, R., McGill, M., Raz, I., et al. The Berlin declaration: a call to action to improve early actions related to type 2 diabetes. How can specialist care help?. Diabetes Res Clin Pract 139 (2018), 392–399.
Holman, R.R., Sourij, H., Califf, R.M., Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes. Lancet 383:9933 (2014), 2008–2017.
Ferrannini, E., DeFronzo, R.A., Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J 36:34 (2015), 2288–2296.
Paneni, F., Luscher, T.F., Cardiovascular protection in the treatment of type 2 diabetes: a review of clinical trial results across drug classes. Am J Med 130:6S (2017), S18–S29.
Schnell, O., Ryden, L., Standl, E., Ceriello, A., D&CVD EASD Study Group. Updates on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol, 16(1), 2017, 128.
American Diabetes Association, 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care 41:Suppl 1 (2018), S73–S85.
Abdul-Ghani, M., DeFronzo, R.A., Is it time to change the type 2 diabetes treatment paradigm? Yes! GLP-1 RAs should replace metformin in the type 2 diabetes algorithm. Diabetes Care 40:8 (2017), 1121–1127.
Scheen, A.J., Charbonnel, B., Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: a critical reappraisal. Diabetes Metab 40:3 (2014), 176–185.
Nauck, M.A., Meier, J.J., Cavender, M.A., Abd El Aziz, M., Drucker, D.J., Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation 136:9 (2017), 849–870.
Scheen, A.J., Cardiovascular outcome studies with incretin-based therapies: comparison between DPP-4 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract 127 (2017), 224–237.
Scheen, A.J., Pharmacological management of type 2 diabetes: what's new in 2017?. Expert Rev Clin Pharmacol 10:12 (2017), 1383–1394.
Thompson, P.L., Davis, T.M.E., Cardiovascular effects of glucose-lowering therapies for type 2 diabetes: new drugs in perspective. Clin Ther 39:5 (2017), 1012–1025.
Roder, M.E., Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential. Ther Adv Chronic Dis 9:1 (2018), 33–50.
Ahmed, H.M., Khraishah, H., Cho, L., Cardioprotective anti-hyperglycaemic medications: a review of clinical trials. Eur Heart J, 2017, 10.1093/eurheartj/ehx668 [Epub ahead of print].
Fioretto, P., Zambon, A., Rossato, M., Busetto, L., Vettor, R., SGLT2 inhibitors and the diabetic kidney. Diabetes Care 39:Suppl 2 (2016), S165–S171.
Wanner, C., Inzucchi, S.E., Lachin, J.M., Fitchett, D., von Eynatten, M., Mattheus, M., et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375:4 (2016), 323–334.
Mann, J.F.E., Orsted, D.D., Brown-Frandsen, K., Marso, S.P., Poulter, N.R., Rasmussen, S., et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 377:9 (2017), 839–848.
Zinman, B., Wanner, C., Lachin, J.M., Fitchett, D., Bluhmki, E., Hantel, S., et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:22 (2015), 2117–2128.
Zinman, B., Inzucchi, S.E., Lachin, J.M., Wanner, C., Fitchett, D., Kohler, S., et al. Empagliflozin and cerebrovascular events in patients with type 2 diabetes mellitus at high cardiovascular risk. Stroke 48:5 (2017), 1218–1225.
Kaul, S., Is the mortality benefit with empagliflozin in type 2 diabetes mellitus too good to be true?. Circulation 134:2 (2016), 94–96.
Fitchett, D., Inzucchi, S.E., Lachin, J.M., Wanner, C., van de Borne, P., Mattheus, M., et al. Cardiovascular mortality reduction with empagliflozin in patients with type 2 diabetes and cardiovascular disease. J Am Coll Cardiol 71:3 (2018), 364–367.
Fitchett, D., Zinman, B., Wanner, C., Lachin, J.M., Hantel, S., Salsali, A., et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J 37:19 (2016), 1526–1534.
Fitchett, D., Butler, J., van de Borne, P., Zinman, B., Lachin, J.M., Wanner, C., et al. Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME(R) trial. Eur Heart J 39:5 (2018), 363–370.
Sattar, N., McLaren, J., Kristensen, S.L., Preiss, D., McMurray, J.J., SGLT2 inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?. Diabetologia 59:7 (2016), 1333–1339.
Wanner, C., Lachin, J.M., Inzucchi, S.E., Fitchett, D., Mattheus, M., George, J., et al. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation 137:2 (2018), 119–129.
Verma, S., Mazer, C.D., Al-Omran, M., Inzucchi, S.E., Fitchett, D., Hehnke, U., et al. Cardiovascular outcomes and safety of empagliflozin in patients with type 2 diabetes mellitus and peripheral artery disease: a subanalysis of EMPA-REG OUTCOME. Circulation 137:4 (2018), 405–407.
Neal, B., Perkovic, V., Mahaffey, K.W., de Zeeuw, D., Fulcher, G., Erondu, N., et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377:7 (2017), 644–657.
Neal, B., Perkovic, V., Mahaffey, K.W., Fulcher, G., Erondu, N., Desai, M., et al. Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS-R trials. Diabetes Obesity Metab 19:7 (2017), 926–935.
Raz, I., Mosenzon, O., Bonaca, M.P., Cahn, A., Kato, E.T., Silverman, M.G., et al. DECLARE-TIMI 58: Participants’ baseline characteristics. Diabetes Obesity Metab 20:5 (2018), 1102–1110.
Cinti, F., Moffa, S., Impronta, F., Cefalo, C.M., Sun, V.A., Sorice, G.P., et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther 11 (2017), 2905–2919.
Cariou, B., Charbonnel, B., Sotagliflozin as a potential treatment for type 2 diabetes mellitus. Expert Opin Investig Drugs 24:12 (2015), 1647–1656.
Kosiborod, M., Cavender, M.A., Fu, A.Z., Wilding, J.P., Khunti, K., Holl, R.W., et al. Lower risk of heart failure and death in patients initiated on SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation 136:3 (2017), 249–259.
Kosiborod, M., Birkeland, K.I., Cavender, M.A., Fu, A.Z., Wilding, J.P., Khunti, K., et al. Rates of myocardial infarction and stroke in patients initiated on SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: results from the CVD-REAL study. Diabetes Obesity Metab, 2018, 10.1111/dom.13299 [Epub ahead of print].
Kosiborod, M., Lam, C.S.P., Kohsaka, S., Kim, D.J., Karasik, A., Shaw, J., et al. Lower cardiovascular risk associated with SGLT-2i in >400,000 patients: the CVD-REAL 2 study. J Am Coll Cardiol 71:23 (2018), 2628–2639.
Birkeland, K.I., Jorgensen, M.E., Carstensen, B., Persson, F., Gulseth, H.L., Thuresson, M., et al. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. Lancet Diabetes Endocrinol 5:9 (2017), 709–717.
Persson, F., Nystrom, T., Jorgensen, M.E., Carstensen, B., Gulseth, H.L., Thuresson, M., et al. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in type 2 diabetes patients (CVD-REAL Nordic) when compared to DPP-4 inhibitors: a multinational observational study. Diabetes Obesity Metab 20:2 (2018), 344–351.
Udell, J.A., Yuan, Z., Rush, T., Sicignano, N.M., Galitz, M., Rosenthal, N., Cardiovascular outcomes and risks after initiation of a sodium glucose co-transporter 2 inhibitor: results from the EASEL population-based cohort study (Evidence for CardiovascularOutcomes With Sodium Glucose Cotransporter 2 Inhibitors in the Real World). Circulation 137:14 (2018), 1450–1459.
Suissa, S., Lower risk of death with SGLT2 inhibitors in observational studies: real or bias?. Diabetes Care 41:1 (2018), 6–10.
Pfeffer, M.A., Claggett, B., Diaz, R., Dickstein, K., Gerstein, H.C., Kober, L.V., et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 373:23 (2015), 2247–2257.
Marso, S.P., Daniels, G.H., Brown-Frandsen, K., Kristensen, P., Mann, J.F., Nauck, M.A., et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375:4 (2016), 311–322.
Scheen, A.J., Semaglutide: a promising new glucagon-like peptide-1 receptor agonist. Lancet Diabetes Endocrinol 5:4 (2017), 236–238.
Marso, S.P., Bain, S.C., Consoli, A., Eliaschewitz, F.G., Jodar, E., Leiter, L.A., et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375:19 (2016), 1834–1844.
Kaneko, M., Narukawa, M., Assessment of cardiovascular risk with glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes using an alternative measure to the hazard ratio. Ann Pharmacother, 1060028018757407, 2018.
Holman, R.R., Bethel, M.A., Mentz, R.J., Thompson, V.P., Lokhnygina, Y., Buse, J.B., et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 377:13 (2017), 1228–1239.
Bethel, M.A., Patel, R.A., Merrill, P., Lokhnygina, Y., Buse, J.B., Mentz, R.J., et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol 6:2 (2018), 105–113.
Scheen, A.J., GLP-1 receptor agonists and cardiovascular protection. Class effect or not?. Diabetes Metab 44:3 (2018), 193–196.
Htike, Z.Z., Zaccardi, F., Papamargaritis, D., Webb, D.R., Khunti, K., Davies, M.J., Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obesity Metab 19:4 (2016), 524–536.
Intarcia press release. Intarcia announces successful cardiovascular safety results in phase 3 FREEDOM-CVO trial for ITCA 650, an investigational therapy for type 2 diabetes. 2016: https://www.intarcia.com/media/press-releases/2016-may-6-cardiovascular-safety.html [latest access May 10, 2018].
Rosenstock, J., Buse, J.B., Azeem, R., Prabhakar, P., Kjems, L., Huang, H., et al. Efficacy and safety of ITCA 650, a novel drug-device GLP-1 receptor agonist, in type 2 diabetes uncontrolled with oral antidiabetes drugs: the FREEDOM-1 trial. Diabetes Care 41:2 (2018), 333–340.
Goldfine, A.B., Assessing the cardiovascular safety of diabetes therapies. N Engl J Med 359:11 (2008), 1092–1095.
Gerstein, H.C., Colhoun, H.M., Dagenais, G.R., Diaz, R., Lakshmanan, M., Pais, P., et al. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obesity Metab 20:1 (2018), 42–49.
Fisher, M., Petrie, M.C., Ambery, P.D., Donaldson, J., Ye, J., McMurray, J.J., Cardiovascular safety of albiglutide in the Harmony programme: a meta-analysis. Lancet Diabetes Endocrinol 3:9 (2015), 697–703.
Ostawal, A., Mocevic, E., Kragh, N., Xu, W., Clinical effectiveness of liraglutide in type 2 diabetes treatment in the real-world setting: a systematic literature review. Diabetes Ther 7:3 (2016), 411–438.
Chatterjee, S., Davies, M.J., Khunti, K., What have we learnt from “real world” data, observational studies and meta-analyses. Diabetes Obesity Metab 20:Suppl 1 (2018), 47–58.
Suissa, S., Mortality Reduction in EMPA-REG OUTCOME trial: beyond the antidiabetes effect. Diabetes Care 41:2 (2018), 219–223.
Ferrannini, E., Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab 26:1 (2017), 27–38.
Scheen, A.J., Reduction in cardiovascular and all-cause mortality in the EMPA-REG OUTCOME trial: a critical analysis. Diabetes Metab 42:2 (2016), 71–76.
Scheen, A.J., Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes : focus on SGLT2 inhibitors and EMPA-REG OUTCOME. Diabetes Res Clin Pract 121 (2016), 204–214.
Inzucchi, S.E., Zinman, B., Fitchett, D., Wanner, C., Ferrannini, E., Schumacher, M., et al. How does empagliflozin reduce cardiovascular mortality? Insights from a mediation analysis of the EMPA-REG OUTCOME trial. Diabetes Care 41:2 (2018), 356–363.
Scheen, A.J., Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 inhibitors. Circ Res 122:10 (2018), 1439–1459.
McMurray, J., EMPA-REG - the “diuretic hypothesis”. J Diabetes Complications 30:1 (2016), 3–4.
Lytvyn, Y., Bjornstad, P., Udell, J.A., Lovshin, J.A., Cherney, D.Z.I., Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation 136:17 (2017), 1643–1658.
Scheen, A.J., Reappraisal of the diuretic effect of empagliflozin in EMPA-REG OUTCOME: comparison with classic diuretics. Diabetes Metab 42:4 (2016), 224–233.
Hallow, K.M., Helmlinger, G., Greasley, P.J., McMurray, J.J.V., Boulton, D.W., Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obesity Metab 20:3 (2018), 479–487.
Ferrannini, E., Mark, M., Mayoux, E., CV protection in the EMPA-REG OUTCOME trial: a “thrifty substrate” hypothesis. Diabetes Care 39:7 (2016), 1108–1114.
Packer, M., Anker, S.D., Butler, J., Filippatos, G., Zannad, F., Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol 2:9 (2017), 1025–1029.
Roussel, R., Steg, P.G., Mohammedi, K., Marre, M., Potier, L., Prevention of cardiovascular disease through reduction of glycaemic exposure in type 2 diabetes: a perspective on glucose-lowering interventions. Diabetes Obesity Metab 20:2 (2018), 238–244.
Verges, B., Charbonnel, B., After the LEADER trial and SUSTAIN-6, how do we explain the cardiovascular benefits of some GLP-1 receptor agonists?. Diabetes Metab, 43(Suppl 1), 2017 2S3–2S12.
Ussher, J.R., Drucker, D.J., Cardiovascular biology of the incretin system. Endocr Rev 33:2 (2012), 187–215.
Ussher, J.R., Drucker, D.J., Cardiovascular actions of incretin-based therapies. Circ Res 114:11 (2014), 1788–1803.
Inzucchi, S.E., Bergenstal, R.M., Buse, J.B., Diamant, M., Ferrannini, E., Nauck, M., et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 58:3 (2015), 429–442.
Gurgle, H.E., White, K., McAdam-Marx, C., SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives. Vasc Health Risk Manag 12 (2016), 239–249.
Consoli, A., Formoso, G., Baldassarre, M.P.A., Febo, F., A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment. Expert Opin Drug Saf, 1–10, 2018.
d'Emden, M., Amerena, J., Deed, G., Pollock, C., Cooper, M.E., SGLT2 inhibitors with cardiovascular benefits: transforming clinical care in Type 2 diabetes mellitus. Diabetes Res Clin Pract 136 (2018), 23–31.
Drexler, A., Can we go beyond surrogates?. J Diabetes 9:11 (2017), 976–977.
Scheen, A.J., GLP-1 receptor agonists and heart failure in diabetes. Diabetes Metab, 43(Suppl 1), 2017 2S13–2S19.
Butler, J., Hamo, C.E., Filippatos, G., Pocock, S.J., Bernstein, R.A., Brueckmann, M., et al. The potential role and rationale for treatment of heart failure with sodium-glucose co-transporter 2 inhibitors. Eur J Heart Fail 19:11 (2017), 1390–1400.
Ponikowski, P., Voors, A.A., Anker, S.D., Bueno, H., Cleland, J.G., Coats, A.J., et al. 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 37:27 (2016), 2129–2200.
Seferovic, P.M., Petrie, M.C., Filippatos, G.S., Anker, S.D., Rosano, G., Bauersachs, J., et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 20:5 (2018), 853–872.
Zhang, L., Zhang, M., Lv, Q., Tong, N., Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and moderate renal function impairment: a systematic review and meta-analysis. Diabetes Res Clin Pract 140 (2018), 295–303.
Seidu, S., Kunutsor, S.K., Cos, X., Gillani, S., Khunti K, for and on behalf of Primary Care Diabetes, Europe. SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: a systematic review and meta-analysis. Prim Care Diabetes 12:3 (2018), 265–283.
Heerspink, H.J.L., Kosiborod, M., Inzucchi, S.E., Cherney, D.Z.I., Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int 94:1 (2018), 26–39.
Scheen, A.J., SGLT2 inhibitors: benefit/risk balance. Curr Diabetes Rep, 16(10), 2016, 92.
Scheen, A.J., SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment. Expert Opin Drug Saf 14:12 (2015), 1879–1904.
Scheen, A.J., Does lower-limb amputation concern all SGLT-2 inhibitors ?. Nat Rev Endocrinol 14:6 (2018), 326–328.
Jabbour, S., Seufert, J., Scheen, A., Bailey, C.J., Karup, C., Langkilde, A.M., Dapagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of safety data from phase IIb/III clinical trials. Diabetes Obesity Metab 20:3 (2018), 620–628.
Davies, M.J., Bain, S.C., Atkin, S.L., Rossing, P., Scott, D., Shamkhalova, M.S., et al. Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): a randomized clinical trial. Diabetes Care 39:2 (2016), 222–230.
Giugliano, D., Maiorino, M.I., Bellastella, G., Esposito, K., Type 2 diabetes and cardiovascular prevention: the dogmas disputed. Endocrine 60:2 (2018), 224–228.
Arnold, S.V., Inzucchi, S.E., Tang, F., McGuire, D.K., Mehta, S.N., Maddox, T.M., et al. Real-world use and modeled impact of glucose-lowering therapies evaluated in recent cardiovascular outcomes trials: An NCDR(R) Research to Practice project. Eur J Prevent Cardiol 24:15 (2017), 1637–1645.
Schernthaner, G., Khunti, K., Lotan, C., Burnier, M., Drexel, H., Prazny, M., Relevance of positive cardiovascular outcome trial results in clinical practice: perspectives from the Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes (ACROSS T2D). Ther Clin Risk Manag 13 (2017), 1569–1576.
Schernthaner, G., Lehmann, R., Prazny, M., Czupryniak, L., Ducena, K., Fasching, P., et al. Translating recent results from the cardiovascular outcomes trials into clinical practice: recommendations from the Central and Eastern European Diabetes Expert Group (CEEDEG). Cardiovasc Diabetol, 16(1), 2017, 137.
Abdul-Ghani, M., DeFronzo, R.A., Del Prato, S., Chilton, R., Singh, R., Ryder, R.E.J., Cardiovascular disease and type 2 diabetes: has the dawn of a new era arrived?. Diabetes Care 40:7 (2017), 813–820.
Frias, J.P., Guja, C., Hardy, E., Ahmed, A., Dong, F., Ohman, P., et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol 4:12 (2016), 1004–1016.
Jabbour, S.A., Frias, J.P., Guja, C., Hardy, E., Ahmed, A., Ohman, P., Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly, or dapagliflozin, added to metformin monotherapy, on body weight, systolic blood pressure, and triglycerides in patients with type 2 diabetes in the DURATION-8 study. Diabetes Obesity Metab 20:6 (2018), 1515–1519.
Harashima, S.I., Inagaki, N., Kondo, K., Maruyama, N., Otsuka, M., Kawaguchi, Y., et al. Efficacy and safety of canagliflozin as add-on therapy to a glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week, open-label, phase IV study. Diabetes Obesity Metab 20:7 (2018), 1770–1775.
De Block, C., SGLT2 inhibitors and GLP-1 receptor agonists: a sound combination. Lancet Diabetes Endocrinol 6:5 (2018), 349–352.
Busch, R.S., Kane, M.P., Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes. Postgrad Med 129:7 (2017), 686–697.
DeFronzo, R.A., Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obesity Metab 19:10 (2017), 1353–1362.