Selecting Antidiabetic Drugs in a Patient with CAD


Dr Shashank R Joshi, Mumbai    04 January 2018

  1. Intensive glycemia control has not demonstrated consistent improvements in macrovascular complications of diabetes, particularly death.
  2. Metformin has demonstrated some CV protection in obese patients with diabetes, and remains the first-line agent of choice, unless contraindicated.
  3. The CV safety of sulfonylurea agents has demonstrated mixed results, and needs more evidence. There may be differences in the CV safety profiles of different sulfonylurea agents.
  4. Thiazolidinediones have demonstrated an increased risk of heart failure.
  5. The regulatory authorities (US-FDA and EMA) have mandated demonstration of CV safety of newer agents for type 2 diabetes.
  6. The newer agents, including DPP4-i, SGLT2-i and GLP1-RA have been evaluated/are under evaluation for CV safety, apart from the newer insulins.
  7. Empagliflozin, Canagliflozin, Liraglutide and Semaglutide have demonstrated evidence of CV protection beyond glycemia control.
  8. Empagliflozin reduced 3P-MACE, CV death, all-cause death and hospitalizations for HF. Canagliflozin reduced 3P-MACE and hospitalizations for HF.
  9. Liraglutide reduced 3P-MACE, CV death and all-cause death. Semaglutide reduced 3P-MACE and nonfatal stroke.
  10. Empagliflozin is the only oral antidiabetic agent, approved by the regulatory authorities including the Indian regulators, for reduction in the risk of CV death in type 2 diabetes patients with established CVD.
  11. The CV benefit of empagliflozin, as observed in EMPA-REG OUTCOME study, applies to patients with known history of CV events, as well as asymptomatic patients of type 2 diabetes with CV disease (>50% blockade in coronary arteries).
  12. Amongst the SGLT2-i agents, the adverse events of lower limb amputations and bone fractures have been observed only with canagliflozin.
  13. CVD REAL is an observational study with inherent channeling bias. Only with the results of the DECLARE-TIMI 58 study, due in 2019, will we have definitive evidence for the cardiovascular benefit and safety of dapagliflozin.
  14. Wherever possible, achievable, affordable and necessary, one should attempt to achieve HbA1c goal, without increasing risk of hypoglycemia or weight-gain. SGLT2-i agents and incretin-based therapies may benefit in this regard.
  15. In patients with type 2 diabetes and established ASCVD, empagliflozin or liraglutide may be considered. Evidence of similar benefit with other SGLT2-i or GLP1-RAs is uncertain.

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