Skip to main content
Top
Published in: Endocrine 2/2018

01-05-2018 | Viewpoint

Type 2 diabetes and cardiovascular prevention: the dogmas disputed

Published in: Endocrine | Issue 2/2018

Login to get access

Abstract

In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo. Other trials with newer diabetes drugs, including empagliflozin and canagliflozin (two sodium-glucose co-transporter-2 inhibitors), liraglutide and semaglutide (two GLP-1 receptor agonists) succeeded in demonstrating CV benefit in people with type 2 diabetes. In the last two decades, the equation “diabetes equals myocardial infarction” have contributed to the development of preventive therapy for risk factors in diabetes. In both primary and secondary prevention, the diabetic patients with high rates of statin and aspirin treatment have improved CV outcome, as compared with non-users. The drugs used to reduce glucose levels in patients with type 2 diabetes seem important for the ultimate cardiovascular outcome: the combination of intensive glycemic control, when safely attainable, with newer diabetes drugs (empagliflozin, canagliflozin, liraglutide, and semaglutide) may decrease the incidence of MACE, nephropathy and retinopathy. Moreover, depending on the drug used, CV mortality and heart failure may also be reduced.
Literature
1.
go back to reference E.W. Gregg, X. Zhuo, Y.J. Cheng, A.L. Albright, K.M. Narayan, T.J. Thompson, Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985–2011: a modeling study. Lancet Diabetes Endocrinol. 2, 867–874 (2014)CrossRefPubMed E.W. Gregg, X. Zhuo, Y.J. Cheng, A.L. Albright, K.M. Narayan, T.J. Thompson, Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985–2011: a modeling study. Lancet Diabetes Endocrinol. 2, 867–874 (2014)CrossRefPubMed
2.
go back to reference D.M. Nathan, J.B. Buse, S.E. Kahn et al., GRADE Study Research Group, Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care 36, 2254–2261 (2013)CrossRefPubMedPubMedCentral D.M. Nathan, J.B. Buse, S.E. Kahn et al., GRADE Study Research Group, Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care 36, 2254–2261 (2013)CrossRefPubMedPubMedCentral
3.
go back to reference F.M. Turnbull, C. Abraira, R.J. Anderson et al., Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52, 2288–2298 (2009)CrossRefPubMed F.M. Turnbull, C. Abraira, R.J. Anderson et al., Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52, 2288–2298 (2009)CrossRefPubMed
4.
go back to reference UK Prospective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837–853 (1998)CrossRef UK Prospective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837–853 (1998)CrossRef
5.
go back to reference The Action to Control Cardiovascular Risk in Diabetes Study Group, Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358, 2545–2559 (2008)CrossRefPubMedCentral The Action to Control Cardiovascular Risk in Diabetes Study Group, Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358, 2545–2559 (2008)CrossRefPubMedCentral
6.
go back to reference The ADVANCE Collaborative Group, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 358, 2560–2572 (2008)CrossRef The ADVANCE Collaborative Group, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 358, 2560–2572 (2008)CrossRef
7.
go back to reference W. Duckworth, C. Abraira, T. Moritz et al., Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 360, 129–139 (2009)CrossRefPubMed W. Duckworth, C. Abraira, T. Moritz et al., Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 360, 129–139 (2009)CrossRefPubMed
8.
go back to reference S. Zoungas, H. Arima, H.C. Gerstein et al., Collaborators on Trials of Lowering Glucose (CONTROL) group, Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomized controlled trials. Lancet Diabetes Endocrinol. 5, 431–377 (2017)CrossRefPubMed S. Zoungas, H. Arima, H.C. Gerstein et al., Collaborators on Trials of Lowering Glucose (CONTROL) group, Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomized controlled trials. Lancet Diabetes Endocrinol. 5, 431–377 (2017)CrossRefPubMed
10.
go back to reference ORIGIN trial Investigators, Basal insulin and cardiovascular and other outcomes in dysglycemia. N. Engl. J. Med. 367, 319–328 (2012)CrossRef ORIGIN trial Investigators, Basal insulin and cardiovascular and other outcomes in dysglycemia. N. Engl. J. Med. 367, 319–328 (2012)CrossRef
11.
go back to reference ORIGIN Trial Investigators, Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the outcome reduction with an initial glargine intervention (ORIGIN) trial. Diabetologia 57, 1325–1331 (2014)CrossRef ORIGIN Trial Investigators, Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the outcome reduction with an initial glargine intervention (ORIGIN) trial. Diabetologia 57, 1325–1331 (2014)CrossRef
12.
go back to reference B.M. Scirica, D.L. Bhatt, E. Braunwald et al., SAVOR-TIMI 53 steering committee and investigators, saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369, 1317–1326 (2013)CrossRefPubMed B.M. Scirica, D.L. Bhatt, E. Braunwald et al., SAVOR-TIMI 53 steering committee and investigators, saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369, 1317–1326 (2013)CrossRefPubMed
13.
go back to reference W.B. White, C.P. Cannon, S.R. Heller et al., EXAMINE Investigators, Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369, 1327–1335 (2013)CrossRefPubMed W.B. White, C.P. Cannon, S.R. Heller et al., EXAMINE Investigators, Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369, 1327–1335 (2013)CrossRefPubMed
14.
go back to reference J.B. Green, M.A. Bethel, P.W. Armstrong et al., TECOS Study Group, Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015)CrossRefPubMed J.B. Green, M.A. Bethel, P.W. Armstrong et al., TECOS Study Group, Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015)CrossRefPubMed
15.
go back to reference O. Mosenzon, G. Leibowitz, D.L. Bhatt et al., Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial. Diabetes Care 40, 69–76 (2017)CrossRefPubMed O. Mosenzon, G. Leibowitz, D.L. Bhatt et al., Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial. Diabetes Care 40, 69–76 (2017)CrossRefPubMed
16.
go back to reference M. Monami, I. Dicembrini, E. Mannucci, Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-analysis of randomized clinical trials. Nutr. Metab. Cardiovasc. Dis. 24, 689–697 (2014)CrossRefPubMed M. Monami, I. Dicembrini, E. Mannucci, Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-analysis of randomized clinical trials. Nutr. Metab. Cardiovasc. Dis. 24, 689–697 (2014)CrossRefPubMed
17.
go back to reference M.A. Pfeffer, B. Claggett, R. Diaz et al., ELIXA investigators, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 373, 2247–2257 (2015)CrossRefPubMed M.A. Pfeffer, B. Claggett, R. Diaz et al., ELIXA investigators, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 373, 2247–2257 (2015)CrossRefPubMed
18.
go back to reference B. Zinman, C. Wanner, J.M. Lachin et al., EMPA-REG OUTCOME Investigators, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)CrossRefPubMed B. Zinman, C. Wanner, J.M. Lachin et al., EMPA-REG OUTCOME Investigators, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)CrossRefPubMed
19.
go back to reference S.P. Marso, G.H. Daniels, K. Brown-Frandsen et al., LEADER Trial Investigators, Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016)CrossRefPubMedPubMedCentral S.P. Marso, G.H. Daniels, K. Brown-Frandsen et al., LEADER Trial Investigators, Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016)CrossRefPubMedPubMedCentral
20.
go back to reference C.C. Low Wang, C.N. Hess, W.R. Hiatt, A.B. Goldfine, Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation 133, 2459–2502 (2016)CrossRefPubMedPubMedCentral C.C. Low Wang, C.N. Hess, W.R. Hiatt, A.B. Goldfine, Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation 133, 2459–2502 (2016)CrossRefPubMedPubMedCentral
21.
go back to reference S.P. Marso, S.C. Bain, A. Consoli et al., SUSTAIN-6 Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834–1844 (2016)CrossRefPubMed S.P. Marso, S.C. Bain, A. Consoli et al., SUSTAIN-6 Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834–1844 (2016)CrossRefPubMed
22.
go back to reference B. Neal, V. Perkovic, K.W. Mahaffey, et al., CANVAS Program Collaborative Group, Canagliflozin and cardiovascular and renal events in type 2 diabetes. N. Engl. J. Med. 377, 644–657 (2017) B. Neal, V. Perkovic, K.W. Mahaffey, et al., CANVAS Program Collaborative Group, Canagliflozin and cardiovascular and renal events in type 2 diabetes. N. Engl. J. Med. 377, 644–657 (2017)
23.
go back to reference C. Wanner, S.E. Inzucchi, J.M. Lachin et al., EMPA-REG OUTCOME Investigators, Empagliflozin and progression of kidney disease in type 2 diabetes. N. Engl. J. Med. 375, 323–334 (2016)CrossRefPubMed C. Wanner, S.E. Inzucchi, J.M. Lachin et al., EMPA-REG OUTCOME Investigators, Empagliflozin and progression of kidney disease in type 2 diabetes. N. Engl. J. Med. 375, 323–334 (2016)CrossRefPubMed
24.
go back to reference S.P. Marso, D.K. McGuire, B. Zinman, et al., DEVOTE Study Group, Efficacy and safety of degludec versus glargine in type 2 diabetes. N. Engl. J. Med. 377, 723–732 (2017) S.P. Marso, D.K. McGuire, B. Zinman, et al., DEVOTE Study Group, Efficacy and safety of degludec versus glargine in type 2 diabetes. N. Engl. J. Med. 377, 723–732 (2017)
25.
go back to reference S.M. Haffner, S. Lehto, T. Rönnemaa, K. Pyörälä, M. Laaks, Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N. Engl. J. Med. 339, 229–234 (1998)CrossRefPubMed S.M. Haffner, S. Lehto, T. Rönnemaa, K. Pyörälä, M. Laaks, Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N. Engl. J. Med. 339, 229–234 (1998)CrossRefPubMed
26.
go back to reference K.K.W. Olesen, M. Madsen, G. Egholm et al., Patients with and without diabetes without significant angiographic coronary artery disease have the same risk of myocardial infarction in a real-world population receiving appropriate prophylactic treatment. Diabetes Care 40, 1103–1110 (2017)CrossRefPubMed K.K.W. Olesen, M. Madsen, G. Egholm et al., Patients with and without diabetes without significant angiographic coronary artery disease have the same risk of myocardial infarction in a real-world population receiving appropriate prophylactic treatment. Diabetes Care 40, 1103–1110 (2017)CrossRefPubMed
Metadata
Title
Type 2 diabetes and cardiovascular prevention: the dogmas disputed
Publication date
01-05-2018
Published in
Endocrine / Issue 2/2018
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1418-y

Other articles of this Issue 2/2018

Endocrine 2/2018 Go to the issue