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HelixTalk Episode #67 - Diabetes: does it cost a “heart” and a leg?

Date posted: September 26, 2017, 6:00 am

In this episode, we discuss new evidence for cardiovascular outcomes in diabetics based on the LEADER trial (liraglutide) and CANVAS trials (canagliflozin). We also discuss the new FDA warning for canagliflozin regarding amputation risk.


Key Concepts

  1. The LEADER trial results showed that liraglutide reduces CV morbidity and mortality in addition to having favorable outcomes for nephropathy. As a result it is now recommended by ADA for diabetic patients with established CV disease or high risk of CV diseases. CV safety trials for other long acting GLP-1 are underway. 
  2. The DEVOTE trial showed that Tresiba (insulin degludec) was non-inferior to insulin glargine in reducing CV outcomes. 
  3. The CANVAS and CANVAS-R trials showed better CV outcomes with canagliflozin than placebo; however, unlike EMPA-reg (with empagliflozin), only 65% of patients had established CVD at baseline. 
  4. Supported by the results of the trials above, the FDA issued a warning against canagliflozin (Invokana) for increased risk of toe or leg amputation with its use in type-2 diabetic patients. 


  1. FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR).
  2. Marso SP, Daniels GH,Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of Medicine. 2016;375:311-322.
  3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. New England Journal of Medicine. 2017;377:644-657.
  4. Marso SP, McGuire DK, Zinman B, et al., on behalf of the DEVOTE Study Group. Efficacy and Safety of Degludec Versus Glargine in Type 2 Diabetes. New England Journal of Medicine. 2017;Jun 12.