Clinical InvestigationsRegional variation of effects of new antidiabetic medications in cardiovascular outcome trials
Section snippets
Methods
We searched PubMed for clinical trials of SGLT2 inhibitors and of GLP-1 receptor agonists assessing effects on CV and/or renal outcomes and included large (>1,000 patients) phase 3 randomized placebo-controlled trials that reported outcomes by region. Terms used for search are given in Supplementary Table 1. We have further compared our review findings with two other metanalysis of SGLT2Is and GLP1RAs.19, 20
Estimated effects by geographic region were available for 14 of 15 trials identified.
Results
Treatment effects on each of the outcomes by geographical region for SGLT2Is in each of the studies is presented in Table 1 and for GLP1RAs in Table 2. Summaries of the available results across all studies are presented in Table 3.
Discussion
The current analysis suggests that there may be some geographical variation with regard to the effects of SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular outcomes. The point estimates for the effects on several CV outcomes are lower in North America and Europe, not reaching statistical significance in these regions, while for all endpoints, the effects of both SGLT2Is and GLP-1RAs in the rest of the world were large and significant (Figure 1). However, except for the effects of
Limitations and conclusion
The current analysis is limited by the public data available on the effects of SGLT2Is and GLP1RAs by geographical region. The availability of more granular data would allow examination of treatment effect moderation by specific countries and even states, as well as exploration of associations with markers of reduced application of standard of care. However, all analyses will be limited by the extent to which standard of care therapy is assessed in the individual trials. Given that prior
Author contribution
Conceptualization: GC, BAD. Investigation: GC, BAD, CE, SS. Formal analysis: BAD, CE, SS. Drafting of manuscript: GC, BAD. All authors reviewed, edited, and approved the final version of the article.
Competing Interests
None.
Funding
None.
References (26)
- et al.
SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials
Lancet
(2020) - et al.
Temelkova-Kurktschiev T, Investigators R. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial
Lancet
(2019) - et al.
Harmony Outcomes c, investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
Lancet
(2018) - et al.
Influence of global region on outcomes in heart failure beta-blocker trials
J Am Coll Cardiol
(2011) - et al.
Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials
Am Heart J
(2021) - et al.
Income level and inequality as complement to geographical differences in cardiovascular trials
Am Heart J
(2019) - et al.
Paradigm HF, Investigators A. Income Inequality and Outcomes in Heart Failure: A Global Between-Country Analysis
JACC Heart Fail.
(2019) - et al.
Investigators E-RO. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
N Engl J Med
(2015) - et al.
Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
N Engl J Med
(2019) - et al.
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
N Engl J Med
(2017)
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
N Engl J Med
Perkovic V. Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups
Circulation
Investigators D-T. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
N Engl J Med
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