Review of randomised trials analyses cardiovascular benefits and risks of GLP-1 receptor agonists in people with type 2 diabetes

By Editor
31st August 2021
Cardiovascular disease, Research Type 2 diabetes

GLP-1 receptor agonists reduced the risk of worsening kidney function in patients with type 2 diabetes, an analysis of randomised trials has found.

The study, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials, set out to address the uncertainty around kidney outcomes and whether benefits extend to exendin-4-based GLP-1 receptor.

It included meta-analysis of new data from AMPLITUDE-O, using a random effects model to estimate overall hazard ratio for major adverse cardiovascular events (MACE).

The team also examined MACE outcome in patient subgroups on the basis of MACE incidence rates in the placebo group, presence or absence of cardiovascular disease, HbA1c level, trial duration, treatment dosing interval, structural homology to human GLP-1 or exendin-4, BMI, age, and eGFR.

They also searched PubMed for eligible trials and meta-analysed data from published randomised placebo-controlled trials testing either injectable or oral GLP-1 receptor agonists in patients with type 2 diabetes.

Eight trials comprising just over 60,000 patients fulfilled the criteria and overall, GLP-1 receptor agonists reduced:

  • MACE by 14%
  • All-cause mortality by 12%
  • Hospital admission for heart failure by 11%
  • Composite kidney outcome by 21%

There was found to be no increase in risk of severe hypoglycaemia, retinopathy, or pancreatic adverse effects.

From the findings, the researchers interpreted that “GLP-1 receptor agonists, regardless of structural homology, reduced the risk of individual MACE components, all-cause mortality, hospital admission for heart failure, and worsening kidney function in patients with type 2 diabetes.”

Led by joint authors Professor Naveed Sattar and Dr Matthew M Y Lee from the Institute of Cardiovascular and Medical Sciences at the University of Glasgow, and Dr Søren L Kristensen, from the Department of Cardiology at Rigshospitalet University Hospital in Denmark, the team included researchers from institutions across several countries.

The study has been published in The Lancet Diabetes and Endocrinology.

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