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Diabetes Update #4 – Venomous lizards help diabetes!

GLP-1 agonists including Byetta, Bydureon (originally found in Gila monster venom) & Saxenda reduce major cardiac events in type 2 diabetes

4th September 2019

Largest study of pooled data shows the drugs cut major CV events by 12% and MI by 9%

Major adverse cardiovascular and renal events are reduced in patients with type 2 diabetes whose treatment includes GLP-1 receptor agonists, according to findings from the largest study of pooled data to date.

The systematic review and meta-analysis of seven trials covering 56,000 people showed that cardiovascular (CV) and all-cause deaths were reduced among those taking the antihyperglycaemics.

In addition, fatal or non-fatal stroke was reduced by 16%, composite major CV events by 12% and myocardial infarction by 9%.

“These benefits were obtained without an increase in risk of severe hypoglycaemia, pancreatic adverse effects or thyroid cancer,” noted the senior author Professor John McMurray from the British Heart Foundation Cardiovascular Research Centre at the University of Glasgow.

GLP-1-receptor agonists also improved long-term blood glucose control, lipid levels, blood pressure and weight, without increasing hypoglycaemic risk.

The treatment reduced hospital admission for heart failure and a composite kidney outcome, including new-onset microalbuminuria, glomerular filtration rate decline or creatinine increase, progression to end-stage kidney disease or death due to kidney disease.

A decrease in macroalbuminuria accounted for most of the improvement in kidney outcomes.

Benefits for different GLP-1 receptor agonists on major adverse CV events were consistent, aside from a suggestion of less effectiveness for extendin-4-based compounds.

“The cardioprotective effects of GLP-1 receptor agonists, as well as reductions in the risk of heart failure and worsening kidney function, represent an important treatment opportunity to reduce morbidity and mortality in patients with type 2 diabetes,” Professor McMurray and colleagues wrote.

The drugs included were: lixisenatide, liraglutide (Saxenda), semaglutide, oral semaglutide, exenatide (Byetta & Bydureon), albiglutide and dulaglutide.

In an accompanying comment, Professor Eberhard Standl, from the Munich Diabetes Research Group eV in Neuherberg, Germany, said the meta-analysis provided robust data that there was no cardiovascular safety issue with GLP-1 receptor agonists.

However, he noted that there was a non-significant benefit observed for primary prevention in a subgroup of nearly 13,000 patients taking GLP-1 receptor agonists that “does not seem particularly convincing”. Most of this evidence came from a single study.

“For the time being, we should be cautious to be really making too strong claims for primary prevention,” he said, adding it was therefore too early to change treatment paradigms.

The study had no funding but several authors reported ties to companies selling GLP-1-receptor agonists.

(Published in Pharmacy News, September 2019)

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