Body weight may influence beneficial effects of SGLT2 inhibitors in patients with diabetes
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Findings from a meta-regression analysis indicated that the beneficial effects of SGLT2 inhibition on CV death and HF hospitalization in patients with diabetes may be related to body weight.
The meta-regression analysis was published in ESC: Heart Failure.
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“It could ... be hypothesized that on CV death or hospitalization due to heart failure endpoints in type 2 diabetes are not exclusively because of these drugs on the heart but because of their known salutary effects on blood glucose, weight and blood pressure control,” Samit Ghosal, MD, FRCP, MSc, endocrinologist at Nightingale Hospital in Kolkata, India, and colleagues wrote. “This analysis was therefore conducted to identify any heterogeneity in the CV death or HF (hospitalization) effect size and if any moderators could explain this variability.”
Ghosal and colleagues conducted a database of the Cochrane Library and identified five relevant studies — including 46,969 patients — to evaluate the relationship between metabolic components affected by SGLT2 inhibitors and a reduction in CV death or HF hospitalizations.
Trials included EMPA-REG, CANVAS, DECLARE TIMI-58, CREDENCE and VERTIS CV.
Researchers reported that the Q statistics (8.06) and associated P value (.09) were indicative that the effect size of SGLT2 inhibitors on CV death or HF hospitalizations varied widely across the five studies. They therefore identified three covariates that could have been predictive of positive outcomes among patients who received SGLT2 inhibition compared with placebo: HbA1c, systolic BP and weight.
Models that compared HbA1c (P = .17) and systolic BP (P = .86) among patients in the SGLT2 inhibitor arm compared with placebo did not explain the variance effect size between the five studies; however, the difference in weight between the SGLT2 inhibitor group compared with placebo group correlated with the observed variance in CV death or HF hospitalization (95% CI, 0.05-0.32; P < .01).
Moreover, an R2 of 1 ruled out sampling error and the coefficient of the weight moderator was 0.18, which was indicative of a positive association between the weight differential and the risk for CV death or HF hospitalization among patients receiving SGLT2 inhibition, according to the study.
“This meta-regression analysis clearly demonstrates that in CV outcomes trials with SGLT2 inhibitors for individuals with type 2 diabetes, body weight is a covariate that is integrally linked to cardiovascular death and heart failure,” the researchers wrote. “It appears that the salutary effects of SGLT2 inhibitors in reducing CV death and HF are related to their effect on body weight. This hypothesis, however, needs further study.”
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