PURLS / PEER REVIEWED

How Do These 3 Diabetes Agents Compare in Reducing Mortality?

Clinician Reviews. 2019 April;29(4):5e-7e

References

1. Zheng S, Roddick A, Aghar-Jaffar R, et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018;319:1580-1591.
2. CDC. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2017.
3. American Diabetes Association. Standards of medical care in diabetes—2019. Diabetes Care. 2019;42(suppl 1):S1-S193.
4. National Institute for Health and Care Excellence. Type 2 diabetes in adults: management. www.nice.org.uk/guidance/ng28. Accessed March 1, 2019.
5. Garber A, Abrahamson M, Barzilay J, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm—2018 executive summary. Endocr Pract. 2018;24:91-120.
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CAVEATS

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 medication classes.

However, there was relatively low heterogeneity among the studies included, 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.

CHALLENGES TO IMPLEMENTATION

Cost, adverse effects, and formulation

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.

ACKNOWLEDGEMENT

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.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[2]:99-101).