medwireNews: A network meta-analysis published in JAMA offers indirect comparisons of the survival benefits associated with use of the most recent antidiabetic agents.
Commenting on the findings for medwireNews, John Wilding (University of Liverpool, UK) highlighted that the reported mortality reductions associated with use of sodium-glucose cotransporter (SGLT)2 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists are comparable to those achieved with antihypertensives or lipid-lowering drugs.
He noted, however, that these antidiabetic drugs are newer and therefore more expensive than blood pressure and cholesterol drugs. “But they won’t be forever.”
The analysis by Sean Zheng (Royal Brompton Hospital, London, UK) and co-workers includes 236 trials, the vast majority of which compared SGLT2 inhibitors, GLP-1 receptor agonists, or dipeptidyl peptidase (DPP)-4 inhibitors with placebo treatment. Just 23 trials were head-to-head comparisons of the different drug classes, with 14 of these pitting GLP-1 receptor agonists against DPP-4 inhibitors.
The overall mortality rates were 3.6%, 3.9%, and 4.4% among patients treated with SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists, respectively, versus 5.2% among those given placebo.
The 236 trials included a total of 176,310 patients, but over half of these (87,162) and around 80% of the cumulative follow-up time (ie, patient–years) came from just nine trials: the cardiovascular (CV) outcome trials.
Wilding pointed out that, for the meta-analysis primary endpoint of all-cause mortality, all the SGLT2 inhibitor CV outcome trials were positive, all the DPP-4 inhibitor trials were neutral, and the GLP-1 analog trials had mixed results. Given their large contribution of data to the meta-analysis, the results of these trials therefore largely dictated the meta-analysis results.
As such, use of SGLT2 inhibitors and of GLP-1 receptor agonists was associated with a significant mortality reduction compared with placebo use, with absolute risk reductions of 1.0% and 0.6%, respectively, and relative risk reductions of 20% and 12%.
DPP-4 inhibitors, by contrast, had no significant effect on mortality when compared with placebo. Thus, for this outcome it was inferior to the other two medication classes, with use of SGLT2 inhibitors and GLP-1 receptor agonists reducing risk by an absolute 0.9% and 0.5%, respectively, and a relative 22% and 14%, compared with DPP-4 inhibitor treatment.
Ranking analysis placed SGLT2 inhibitors as likely to be the most effective for reducing the risk for all-cause and cardiovascular mortality, heart failure, and myocardial infarction, whereas GLP-1 receptor agonists came out on top for unstable angina and stroke.
However, Wilding cautioned against placing too much weight on this finding, describing the class comparison as “flawed,” because of the differences – both pharmacologic and in trial design – within the GLP-1 analog class. The analysis is therefore “comparing a class where the drugs studies are very similar in their effects, to one where some of the drugs appear ineffective, thus diluting the overall beneficial effects of those that work,” he said.
He added that whether the reported effects of the GLP-1 receptor agonists represent a class effect remains an open question.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group
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