J Korean Diabetes.  2016 Mar;17(1):1-5. 10.4093/jkd.2016.17.1.1.

Review of Cardiovascular Effects of Antidiabetic Drugs and Recent Cardiovascular Outcome Trials

Affiliations
  • 1Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. shoney@inha.ac.kr

Abstract

Cardiovascular disease is a major cause of morbidity and mortality in people with type 2 diabetes. Therefore, the prevention of cardiovascular diseases is of great importance in these patients. Antidiabetic drugs may have cardiovascular effects independent of their glycemic effects. The highly publicized meta-analysis of rosiglitazone has triggered much concern about the cardiovascular effects of antidiabetic drugs. Since 2008, the US Food and Drug Administration (FDA) has required that all new antidiabetic drugs show proof of an acceptable cardiovascular risk profile. Because there is a lack of well-designed definitive studies, the cardiovascular risk/benefit is not definite in many drugs. Large randomized trials assessing the cardiovascular risk of antidiabetic drugs have been recently completed or are ongoing. The first novel drug class designated after 2008 is the dipeptidyl peptidase-4 (DPP-4) inhibitors. Trials of DPP-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown a neutral effect on cardiovascular disease. Empagliflozin, a sodium-glucose co-transporter 2 inhibitor, significantly decreased the incidence of the primary cardiovascular end point, especially decreasing cardiovascular death and hospital admission for heart failure. Ongoing and future studies will provide better insight about the effects of each class and individual drug on cardiovascular disease.

Keyword

Antidiabetic drugs; Cardiovascular disease; Type 2 diabetes

MeSH Terms

Cardiovascular Diseases
Glucagon-Like Peptide 1
Heart Failure
Humans
Hypoglycemic Agents*
Incidence
Mortality
United States Food and Drug Administration
Glucagon-Like Peptide 1
Hypoglycemic Agents

Reference

References

1. Preis SR, Pencina MJ, Hwang SJ, D'Agostino RB Sr, Savage PJ, Levy D, Fox CS. Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the Framingham Heart Study. Circulation. 2009; 120:212–20.
Article
2. Emerging Risk Factors Collaboration. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative metaanalysis of 102 prospective studies. Lancet. 2016; 375:2215–22.
3. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979; 241:2035–8.
Article
4. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352:854–65.
5. Action to Control Cardiovascular Risk in Diabetes Study Group. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, IsmailBeigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358:2545–59.
6. ADVANCE Collaborative Group. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358:2560–72.
7. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD. VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360:129–39.
Article
8. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359:1577–89.
Article
9. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007; 356:2457–71.
Article
10. Joffe HV, Parks MH, Temple R. Impact of cardiovascular outcomes on the development and approval of medications for the treatment of diabetes mellitus. Rev Endocr Metab Disord. 2010; 11:21–30.
Article
11. Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010; 12:648–58.
Article
12. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I. SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013; 369:1317–26.
Article
13. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F. EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013; 369:1327–35.
Article
14. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR. TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015; 373:232–42.
Article
15. Marx N, Rosenstock J, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, Espeland MA, Bluhmki E, Mattheus M, Ryckaert B, Patel S, Johansen OE, Woerle HJ. Design and baseline characteristics of the cardiovascular outcome trial of linagliptin versus glimepiride in type 2 diabetes (CAROLINA®). Diab Vasc Dis Res. 2015; 12:164–74.
Article
16. Lorber D. GLP-1 receptor agonists: effects on cardiovascular risk reduction. Cardiovasc Ther. 2013; 31:238–49.
17. Mundil D, Cameron-Vendrig A, Husain M. GLP-1 receptor agonists: a clinical perspective on cardiovascular effects. Diab Vasc Dis Res. 2012; 9:95–108.
Article
18. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, Lawson FC, Ping L, Wei X, Lewis EF, Maggioni AP, McMurray JJ, Probstfield JL, Riddle MC, Solomon SD, Tardif JC. ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015; 373:2247–57.
Article
19. Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and metaanalysis. Ann Intern Med. 2013; 159:262–74.
20. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117–28.
Article
21. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008; 358:580–91.
Article
Full Text Links
  • JKD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr