Cardiovascular and Renal Benefits of Novel Diabetes Drugs by Baseline Cardiovascular Risk: A Systematic Review, Meta-analysis, and Meta-regression

José M. Rodriguez-Valadez*, Malak Tahsin, Kirsten E. Fleischmann, Umesh Masharani, Joseph Yeboah, Meyeon Park, Lihua Li, Ellerie Weber, Yan Li, Asem Berkalieva, Wendy Max, M. G.Myriam Hunink, Bart S. Ferket*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

BACKGROUND: Eligibility for glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been expanded to patients with diabetes at lower cardiovascular risk, but whether treatment benefits differ by risk levels is not clear. PURPOSE: To investigate whether patients with varying risks differ in cardiovascular and renal benefits from GLP-1RA and SGLT2i with use of meta-analysis and meta-regression. DATA SOURCES: We performed a systematic review using PubMed through 7 November 2022. STUDY SELECTION: We included reports of GLP-1RA and SGLT2i confirmatory randomized trials in adult patients with safety or efficacy end point data. DATA EXTRACTION: Hazard ratio (HR) and event rate data were extracted for mortality, cardiovascular, and renal outcomes. DATA SYNTHESIS: We analyzed 9 GLP-1RA and 13 SGLT2i trials comprising 154,649 patients. Summary HRs were significant for cardiovascular mortality (GLP-1RA 0.87 and SGLT2i 0.86), major adverse cardiovascular events (0.87 and 0.88), heart failure (0.89 and 0.70), and renal (0.84 and 0.65) outcomes. For stroke, efficacy was significant for GLP-1RA (0.84) but not for SGLT2i (0.92). Associations between control arm cardiovascular mortality rates and HRs were nonsignificant. Five-year absolute risk reductions (0.80-4.25%) increased to 11.6% for heart failure in SGLT2i trials in patients with high risk (Pslope < 0.001). For GLP1-RAs, associations were nonsignificant. LIMITATIONS: Analyses were limited by lack of patient-level data, consistency in end point definitions, and variation in cardiovascular mortality rates for GLP-1RA trials. CONCLUSIONS: Relative effects of novel diabetes drugs are preserved across baseline cardiovascular risk, whereas absolute benefits increase at higher risks, particularly regarding heart failure. Our findings suggest a need for baseline risk assessment tools to identify variation in absolute treatment benefits and improve decision-making.

Original languageEnglish
Pages (from-to)1300-1310
Number of pages11
JournalDiabetes Care
Volume46
Issue number6
DOIs
Publication statusPublished - 1 Jun 2023

Bibliographical note

Funding Information:
Acknowledgments. The authors thank Carrie Levinson, Reference & Instruction Librarian, Mount Sinai Health System, who provided expertise for developing the search strategy. Funding. Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award no. R01HL153456. M.G.M.H. has received research funding from the Netherlands Organization for Health Research and Development, the German Innovation Fund, and Netherlands Educational Grant (“Studie Voorschot Middelen”), and additional research funding from the Gordon and Betty Moore Foundation. K.E.F. is the recipient of an Innovative Clinical or Translational Science award from the American Diabetes Association (1-18-ICTS-041).

Funding Information:
Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award no. R01HL153456. M.G.M.H. has received research funding from the Netherlands Organization for Health Research and Development, the German Innovation Fund, and Netherlands Educational Grant (“Studie Voorschot Middelen”), and additional research funding from the Gordon and Betty Moore Foundation. K.E.F. is the recipient of an Innovative Clinical or Translational Science award from the American Diabetes Association (1-18-ICTS-041).

Publisher Copyright:
© 2023 by the American Diabetes Association.

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