Series: Cardiovascular outcome trials for diabetes drugs Degludec and DEVOTE

Authors

  • Miles Fisher Glasgow Royal Infirmary

DOI:

https://doi.org/10.15277/bjd.2021.302

Keywords:

diabetes, cardiovascular outcome trial, degludec, glargine

Abstract

DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardio-vascular Events) was an FDA-mandated cardiovascular outcome trial and was the first – and at present the only – completed trial comparing two insulins. DEVOTE compared insulin degludec and insulin glargine (U100) in 7,637 people with type 2 diabetes with established cardiovascular disease, chronic kidney disease, or both, and older diabetic patients with increased cardiovascular risk. DEVOTE demonstrated non-inferiority for major cardiovascular events (MACE), a composite of death from cardiovascular causes, non-fatal myocardial infarction and non-fatal stroke, with a pre-specified non-inferiority margin of 1.3. At 24 months the mean HbA1c was similar in the two groups. Mean fasting plasma glucose was significantly lower in the degludec group than in the glargine group, and pre-specified severe hypoglycaemia was also significantly lower in the degludec group. DEVOTE satisfied the FDA cardiovascular safety requirements for new antidiabetic therapies.

Author Biography

Miles Fisher, Glasgow Royal Infirmary

consultant

References

Chong WH, Yanoff LB, Andraca-Carrera E, Thanh Hai M. Assessing the safety of glucose-lowering drugs – a new focus for the FDA. N Engl J Med 2020;383:1199–202. https://doi.org/10.1056/NEJMp2004889

Fisher M. Saxagliptin and SAVOR-TIMI 53. Br J Diabetes 2019;19:34–6. https://doi.org/10.15277/bjd.2019.213

Fisher M. Alogliptin and EXAMINE. Br J Diabetes 2019;19:133–5. https://doi.org/10.15277/bjd.2019.230

Fisher M. Lixisenatide and ELIXA. Br J Diabetes 2020;20:52–4. https://doi.org/10.15277/bjd.2020.241

Fisher M. Sitagliptin and TECOS. Br J Diabetes 2020;20:55–7. https://doi.org/10.15277/bjd.2020.242

Fisher M. Empagliflozin and EPA-REG OUTCOME. Br J Diabetes 2020; 20:138–41. https://doi.org/10.15277/bjd.2020.254

Fisher M. Liraglutide and LEADER. Br J Diabetes 2020;20:142–4. https://doi.org/10.15277/bjd.2020.267

Fisher M. Semaglutide and SUSTAIN-6. Br J Diabetes 2021;21 (in press).

ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012;367:319–28. https://doi.org/10.1056/NEJMoa1203858

Marso SP, McGuire DK, Zinman B, et al, for the DEVOTE Study Group. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med 2017;377:723–32. https://doi.org/10.1056/NEJMoa1615692

Marso SP, McGuire DK, Zinman B, et al. Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardio-vascular Events) – DEVOTE 1. Am Heart J 2016;179:175–83. https://doi.org/10.1016/j.ahj.2016.06.004

Pratley RE, Husain M, Lingvay I, et al, on behalf of the DEVOTE Study Group. Heart failure with insulin degludec versus glargine U100 in patients with type 2 diabetes at high risk of cardiovascular disease: DEVOTE 14. Cardiovasc Diabetol 2019;18:156. https://doi.org/10.1186/s12933-019-0960-8

Lane W, Bailey TS, Gerety G, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycaemia in patients with type 1 diabetes. The SWITCH 1 randomized clinical trial. JAMA 2017;318:33–44. https://doi.org/10.1001/jama.2017.7115

Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycaemia in patients with type 2 diabetes. The SWITCH 2 randomized clinical trial. JAMA 2017;318:45–56. https://doi.org/10.1001/jama.2017.7117

Pieber TR, Marso SP, McGuire DK, et al, on behalf of the DEVOTE Study Group. DEVOTE 3: temporal relationship between severe hypoglycaemia, cardiovascular outcomes and mortality. Diabetologia 2018; 61:58–65. https://doi.org/10.1007/s00125-017-4422-0

Pratley RE, Emerson SS, Franek E, et al, on behalf of the DEVOTE Study Group. Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: results from DEVOTE (DEVOTE 7). Diabetes Obes Metab 2019;21:1625–33. https://doi.org/10.1111/dom.13699

Heller S, Lingvay I, Marso SP, et al, Devote Study Group. Risk of severe hypoglycaemia and its impact in type 2 diabetes in DEVOTE. Diabetes Obes Metab 2020;22:2241–7. https://doi.org/10.1111/dom.14049

Amod A, Buse JB, McGuire DK, et al. on behalf of the DEVOTE Study Group. Glomerular filtration rate and associated risks of cardiovascular events, mortality, and hypoglycemia in patients with type 2 diabetes; secondary analysis (DEVOTE 11). Diabetes Ther 2020;11:53–70. https://doi.org/10.1007/s13300-019-00715-x

Amod A, Buse JB, McGuire DK, et al, on behalf of the DEVOTE Study Group. Risk factors for kidney disorders in patients with type 2 diabetes at high cardiovascular risk: an exploratory analysis (DEVOTE 12). Diab Vasc Dis Res 2020;17:1479164120970933. https://doi.org/10.1177/1479164120970933

Pollock RF, Valentine WJ, Marso SP, et al, on behalf of the DEVOTE Study Group. Long-term cost-effectiveness of insulin degludec versus insulin glargine U100 in the UK: evidence from the basal-bolus subgroup of the DEVOTE trial (DEVOTE 16). Appl Health Econ Health Policy 2019; 17:615–27. https://doi.org/10.1007/s40258-019-00494-3

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Published

2021-05-28

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