How do these 3 diabetes agents compare in reducing mortality?

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A lack of head-to-head RCTs

This study was a network meta-analysis that included many trials, the majority of which compared SGLT-1 inhibitors, GLP-1 agonists, and DPP-4 inhibitors with controls rather than to one another. Thus, the findings are not derived from a robust base of head-to-head RCTs involving the 3 classes of medication.

For another diabetes-related PURL, see “Bariatric surgery + medical therapy: Effective Tx for T2DM?"

However, there was relatively low heterogeneity among the studies included (I2=12), which lends strength to the meta-analysis.6 Patients with the highest baseline CV risk likely gleaned the greatest benefits from these treatments and may have driven much of the observed mortality reduction. This may limit the generalizability of the results to people with low CV risk. The comparative effectiveness and risk for adverse effects among individual medications within each class is unknown because the analysis was completed by drug class in order to adequately power the study to detect treatment effects.


Cost, adverse effects, and formulation may represent challenges

The cost of SGLT-2 inhibitors and GLP-1 agonists may present challenges to patients wishing to use these options. Additionally, the increased risk for genital infections with SGLT-2 inhibitors, and of overall adverse effects (many of which were gastrointestinal) with GLP-1 agonists, must be considered. Lastly, the injectable formulation of GLP-1 agonists may present a barrier to patients’ ability and willingness to effectively administer these agents.


The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

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