Meta-analysis underscores individual risk profile impact on GLP-1, SGLT2 benefits
medwireNews: A network meta-analysis highlights the impact of individual risk profiles on the absolute benefits offered by glucagon-like peptide (GLP)-1 receptor agonists and sodium-glucose cotransporter (SGLT)2 inhibitors for people with type 2 diabetes.
For all-cause mortality, for example, 5 years of treatment with a GLP-1 receptor agonist would result in an estimated 24 fewer deaths per 1000 people with very high vascular risk, but just two fewer for people at very low risk.
The corresponding numbers for 5 years of SGLT2 inhibitor treatment were 48 versus five fewer events per 1000 people treated.
The study, published in The BMJ and conducted as part of the BMJ Rapid Recommendations process, included 764 randomized controlled trials involving a total of 421,346 people with type 2 diabetes; trial sizes ranged from 16 to 17,160 participants.
When compared directly against each other, as a network meta-analysis allows, SGLT2 inhibitors and GLP-1 receptor agonists were equivalent for reducing the risk for cardiovascular mortality, nonfatal myocardial infarction, and kidney failure. Both medication classes reduced the risk for these endpoints when compared with placebo.
But SGLT2 inhibitors were superior to GLP-1 receptor agonists for all-cause mortality and for heart failure hospitalization at all levels of vascular risk, resulting in 16 and 24 fewer events per 1000 high-risk people, for example.
By contrast, GLP-1 receptor agonists were more effective for preventing nonfatal stroke, again at all risk levels, with 18 more events occurring per 1000 high-risk people if an SGLT2 inhibitor was used instead. SGLT2 inhibitors did not reduce the risk for stroke when compared against placebo, whereas GLP-1 receptor agonists did.
Treatment with an SGLT2 inhibitor agonist rather than a GLP-1 receptor resulted in significantly greater weight loss (although both reduced bodyweight versus placebo), slightly more serious hyperglycemic events, and markedly more instances of genital infection. Use of GLP-1 receptor agonists was associated with an increased risk for severe gastrointestinal events versus placebo.
“In the absence of head-to-head trials, we […] found high certainty evidence for notable differences between SGLT-2 inhibitors and GLP-1 receptor agonists,” write Giovanni Strippoli (University of Bari, Italy) and study co-authors.
They say that “[i]mportantly, the absolute benefits for cardiovascular and renal outcomes varied substantially for patients, depending on their absolute cardiovascular risk,” and stress the “clear implications for clinical practice.”
The team’s findings will provide the basis for a forthcoming BMJ Rapid Recommendation, and the results of their medication class comparisons can be explored in the MAGICapp.
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