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Anti-Diabetic Agents and Heart Failure　- Response to the CARMELINA Study

Motoaki Sano1

  • 1Department of Cardiology, Keio University School of Medicine Tokyo Japan.

Circulation Reports
|March 11, 2021
PubMed

Insights

Certain anti-diabetic drugs offer cardiovascular benefits for type 2 diabetes patients. Sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists show promise in preventing heart failure and arteriosclerotic events.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Cardiovascular outcome trials (CVOTs) demonstrate that some anti-diabetic medications improve cardiovascular health in type 2 diabetes (T2D).
  • Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown distinct cardiovascular benefits.
  • Dipeptidyl peptidase 4 (DPP-4) inhibitors are commonly used add-on therapies, with general cardiovascular safety but potential differences in heart failure risk.

Purpose of the Study:

  • To evaluate the cardiovascular safety of linagliptin, a DPP-4 inhibitor, in a T2D population with kidney dysfunction.
  • To compare the effects of SGLT2i and GLP-1RA on heart failure hospitalization and arteriosclerotic events.
  • To explore the potential for combination therapy to prevent both heart failure and arteriosclerotic events.

Main Methods:

  • Analysis of cardiovascular outcome trials (CVOTs) for SGLT2i (empagliflozin, canagliflozin, dapagliflozin) and GLP-1RA (liraglutide, semaglutide, albiglutide).
  • Review of existing literature on DPP-4 inhibitors (sitagliptin, alogliptin, saxagliptin) regarding cardiovascular safety and heart failure risk.
  • Focus on the CARMELINA study investigating linagliptin's safety in T2D patients with renal impairment.

Main Results:

  • SGLT2i significantly reduce heart failure hospitalizations and kidney function decline.
  • GLP-1RA, particularly human analogs, effectively suppress arteriosclerotic diseases like stroke and myocardial infarction.
  • DPP-4 inhibitors generally do not increase arteriosclerotic risk, but heart failure safety may vary; linagliptin's safety in T2D with kidney dysfunction was specifically examined.

Conclusions:

  • Combination therapy with SGLT2i and GLP-1RA may offer comprehensive protection against both heart failure and arteriosclerotic events in T2D.
  • DPP-4 inhibitors are valuable add-on treatments, but careful consideration of individual drug profiles, especially concerning heart failure, is warranted.
  • The CARMELINA study provides crucial data on linagliptin's cardiovascular safety in a high-risk T2D subgroup with kidney dysfunction.
Keywords:
Cardiovascular outcomeDipeptidyl peptidase 4 inhibitorHeart failureSodium glucose cotransporter 2 inhibitorType 2 diabetes mellitus

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