medwireNews: Findings from a meta-analysis indicate that Asian people may derive greater cardiovascular (CV) benefit from sodium-glucose cotransporter (SGLT)2 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists than their White counterparts.
Naveed Sattar, from the University of Glasgow in the UK, and co-authors report in Diabetes Care that the two antihyperglycemic drug classes appear to have “differential treatment effects” by race that favored Asian participants.
The team collated data from four diabetes trials of SGLT2 inhibitors that recorded major adverse CV events (MACE) in people with type 2 diabetes – EMPA-REG OUTCOME, CANVAS, CANVAS-R, and VERTIS CV. The hazard ratio (HR) for MACE in the 3298 Asian participants was 0.81, a value that was statistically comparable to the HR of 0.90 for the 20,258 White patients.
But analysis of the DAPA-HF and EMPEROR-Reduced SGLT2 inhibitor trials for patients with heart failure (HF) and a reduced ejection fraction gave a HR for CV death or HF hospitalization of 0.60 with SGLT2 inhibitor therapy versus placebo among the 1788 Asian participants and 0.82 among the 5962 White participants, a difference in HR that resulted in a significant p value for interaction.
The researchers also examined the relationship between race and outcome for six trials of GLP-1 receptor agonists that reported MACE in patients with type 2 diabetes, namely LEADER, SUSTAIN-6, EXSCEL, HARMONY OUTCOMES, REWIND, and PIONEER.
The HR for MACE with GLP-1 receptor agonist therapy versus placebo was 0.68 for the 4195 Asian participants of these trials versus 0.87 among the 37,530 White individuals, again giving a significant p value for interaction.
“Because the interaction between Asian race and outcome seems consistent across different groups of studies, particular[ly] for the GLP-1 [receptor agonist] class, it seems unlikely that random variation in baseline characteristics between trial arms explains the results,” Sattar et al comment.
But they emphasize that the meta-analysis is “hypothesis generating” and note several limitations, such as the inability to differentiate between Asian subpopulations with differing CV disease characteristics.
In addition, Asian participants may have been less likely than their White counterparts to have received preventative therapy for MACE, potentially leading to an “accentuated benefit” with SGLT2 inhibitor or GLP-1 receptor agonist therapy, “although even if this were true, such an observation would be clinically important,” the authors remark.
Sattar et al also postulate about the possibility of biologic differences between races that might affect antihyperglycemic medication efficacy, perhaps related to the earlier diabetes onset found among Asian populations.
“This is speculative, however, and more work is needed to determine if differences are genuine and, if so, identify potential mechanisms, including effects on multiple risk pathways,” they write.
The authors advise that future trials should record Asian race “with greater granularity,” allowing analyses in addition to geographic region.
“We also suggest a need for more outcome- specific trials in Asian countries to further explore and validate the findings for GLP-1 [receptor agonists],” they advise.
“The findings of these analyses are relevant to the design, data capture, and reporting of future CV [outcome trials].”
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