About 80,000 diabetes patients were analyzed from 8 clinical trials.
Authors found that GLP1 agonists and SGLT2 inhibitors prevented cardiovascular events (MACE) equally by 14% in those with established CVD. However, both classes of medications did not appear to be effective in reducing MACE in adults with diabetes but without established CVD.
SGLT2 inhibitors showed superior results compared to GLP1 agonists in regard to preventing hospitalizations for heart failure or severe kidney disease progression, such as end-stage-renal disease or death.
If cost, side effects, drug interactions and contraindications allow, diabetes patients would greatly benefit from these therapies on three fronts; glucose control, heart and kidney disease prevention.
Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as two new classes of anti-hyperglycemic agents that also reduce cardiovascular risk.
The relative benefits in patients with and without established atherosclerotic cardiovascular disease (ASCVD) for different outcomes with these classes of drugs remain undefined.
We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases.
The primary outcomes were: the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and progression of kidney disease (PKD).
In total, data from 8 trials and 77,242 patients, 42,920 (55.6%) in GLP1-RA trials and 34,322 (44.4%) in SGLT2i trials, were included.
- Both drug classes reduced MACE in a similar magnitude with GLP1RA reducing the risk by 12% (HR 0.88, p<0.001) and SGLT2i by 11% (HR 0.89, p=0.001).
- For both drug classes, this treatment effect was restricted to a 14% reduction in those with established ASCVD (HR 0.86, P=0.002) whereas no effect was seen in patients without established ASCVD (HR 1.01, P=0.81).
- SGLT2i reduced HHF by 31% (HR 0.69, P<0.001)
- GLP1-RA did not have a significant effect in reducing HHF (HR 0.93, p=0.20).
- Both GLP1-RA (HR 0.82, p<0.001) and SGLT2i (HR 0.62, p<0.001) reduced the risk of progression of kidney disease (PKD) including microalbuminuria,
- But only SGLT2i reduced the risk of worsening eGFR, end-stage kidney disease, or renal death (HR 0.55, <0.001).
In trials reported to date, 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 PKD (progression of kidney disease)
Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with T2DM.