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Comparison of the Effects of GLP1-RA and SGLT2i

Apr 9, 2019
 
Editor: Steve Freed, R.PH., CDE

Author: Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy

GLP1-RA and SGLT2i reduce atherosclerotic major cardiovascular events (MACE) to a similar degree in patients with established ASCVD.

Two drug classes, glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i), have been shown to significantly reduce the risk of major cardiovascular events (MACE), the composite of myocardial infarction, stroke, and cardiovascular death. Both drug classes have modest and relatively similar reductions of HbA1c and therefore appear to exert their beneficial cardiovascular effects independent of glucose management through their individual pleiotropic properties.

The relative benefits in patients with and without established atherosclerotic cardiovascular disease (ASCVD) for different outcomes with these classes of drugs remain undefined.

A recent meta-analysis by T.A. Zelniker et al of cardiovascular outcomes trials was designed to compare and contrast the clinical benefit of GLP1-RA and SGLT2i in patients with and without established ASCVD. In total, data from eight trials and 77,242 patients, 42,920 (55.6%) in GLP1-RA trials and 34,322 (44.4%) in SGLT2i trials, were included. The primary outcomes were: the composite of myocardial infarction (MI), stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and progression of kidney disease.

The meta-analysis showed that both GLP1-RA and SGLT2i reduce the risk of MACE by approximately 14% in patients with known ASCVD, whereas neither reduces the risk of MACE in patients without established ASCVD. Both classes reduced the risk of MI and CV death, but only GLP1-RA reduced the risk of stroke. In contrast, SGLT2 inhibitors reduced the relative risk of hospitalization for heart failure (HHF) by 31%, whereas there was only a non-significant 7% relative risk reduction with GLP1-RA.

While GLP1-RA has been found to reduce kidney events by its reduction in microalbuminuria, microalbuminuria is a surrogate marker and may even be absent in patients with reduced estimated glomerular filtration rate (eGFR) and mostly reflects risk for diabetic kidney disease and cardiovascular disease. Therefore when excluding microalbuminuria, GLP1-RA had a non-significant relative reduction by 8% while SGLT2i  showed robust relative risk reductions by 45% for the composite of reductions in eGFR, end-stage kidney disease, and death due to renal causes.

Natriuresis and inhibition of the tubule-glomerular feedback by SGLT2i may play a central role and explain the observed reduction in hospitalization for heart failure and the delayed progression of diabetic kidney disease.

The study concluded that GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established ASCVD, whereas SGLT2i have a more marked effect on preventing HHF and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with type 2 diabetes.

Practice Pearls:

  • GLP1-RA and SGLT2i reduce the risk of major cardiovascular events by approximately 14% in patients with known ASCVD, whereas neither reduces the risk of major cardiovascular events in patients without established ASCVD.
  • SGLT2 inhibitors have a more marked effect on preventing hospitalization for heart failure and progression of kidney disease.
  • When considering these therapies for patients with type 2 diabetes, providers should put these factors into consideration in the decision making process.

Reference:

Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Furtado RHM, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Co-Transporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials. Circulation. 2019 Feb 21.

Dahlia Elimairi, Pharm D student UC Denver Skaggs School of Pharmacy