Updated meta-analysis addresses exendin-4 GLP-1 receptor agonist doubts
medwireNews: An updated meta-analysis including AMPLITUDE-O supports the cardioprotective effects of glucagon-like peptide (GLP)-1 receptor agonists regardless of whether they are human- or exendin–4-based.
The analysis from Naveed Sattar (University of Glasgow, UK) and colleagues, published in The Lancet Diabetes & Endocrinology, included eight placebo-controlled trials with a total 60,080 participants.
Three trials (ELIXA, EXSCEL, and AMPLITUDE-O) involved medications with an exendin-4 structural basis, whereas the medications used in the other five trials (LEADER, SUSTAIN-6, Harmony Outcomes, REWIND, and PIONEER 6) are based on human GLP-1.
Writing in a linked commentary, Darren McGuire (University of Texas Southwestern Medical Center, Dallas, USA) and Neha Pagidipati (Duke University Medical Center, Durham, North Carolina, USA) say: “Although initially it might seem minimally incremental to add data from only one trial to the seven trials previously analysed, several key issues that are addressed and clarified by the addition of the AMPLITUDE-O data make this paper very important.”
Overall, treatment with a GLP-1 receptor agonist was associated with a significant 14% reduction in the risk for major adverse cardiovascular events (nonfatal myocardial infarction or stroke, or cardiovascular death), with no significant difference in effect size according to the medications’ structural basis.
The number needed to treat was 65 to prevent one outcome event over a weighted average median follow-up of 3.0 years.
Treatment with a GLP-1 receptor agonist significantly reduced the risk for a range of individual outcomes, including fatal or nonfatal stroke by 17%, as highlighted by McGuire and Pagidipati who note that to date only REWIND has reported such an effect.
“In the context of the trials considered, in which background atherosclerotic cardiovascular disease risk reduction therapies were highly prevalent and risk factors were well managed, this incremental risk reduction for stroke by GLP1 receptor agonists is clinically important,” they observe.
There was also a significant 11% reduction in the risk for heart failure hospitalization, but here the commentators advise caution, noting that this “is completely driven by results from two trials [Harmony Outcomes and AMPLITUDE-O] evaluating formulations not approved for clinical use because of industry decisions to halt development.”
GLP-1 receptor agonist treatment was additionally associated with a risk reduction of 13% for cardiovascular death, 12% for all-cause mortality, 10% for fatal or nonfatal myocardial infarction, and of 21% for adverse renal outcomes in the six trials that provided data on this outcome.
The researchers conclude that clinical use of these medications represents “an important treatment opportunity to reduce morbidity and mortality in patients with type 2 diabetes.”
However, McGuire and Pagidipati note that GLP-1 receptor agonists “remain woefully underused in contemporary clinical practice.”
They attribute this partly to their cost, but also to “the challenge of busy practitioners keeping up with the data and clinical inertia, both of which can be addressed with systematic educational programmes and processes.”
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