Prescribe SGLT2 inhibitors, GLP-1 receptor agonists ‘as early as possible’ for CV benefit
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Adults with type 2 diabetes assigned an SGLT2 inhibitor or a GLP-1 receptor agonist during cardiovascular outcomes trials derived benefit from the therapies regardless of whether they were prescribed insulin, according to a meta-analysis.
In an analysis of data across eight large, multiyear CV outcomes trials for three classes of diabetes agents, researchers also found that participants using insulin at baseline when assigned other diabetes drugs were more likely to experience a major adverse CV event vs. those assigned the drugs who did not use insulin.
“SGLT2 inhibitors and GLP-1 agonists should be used as early as possible in the diabetes course to provide the most cardiac benefit,” Joanna Khatib, MBBS, an endocrinology fellow at Tulane University School of Medicine, told Healio. “Even when insulin is used, these classes of medications still provide benefits.”
In a meta-analysis, Khatib and colleagues assessed major adverse CV events from eight recent CV outcome trials for SGLT2 inhibitors, GLP-1 receptor agonists and DPP-IV inhibitors: DECLARE, EMPA-REG, EXSCEL, HARMONY, LEADER, SUSTAIN-6, EXAMINE and SAVOR-TIMI 53. Researchers compared CV outcomes for participants from subgroups that were already prescribed insulin at baseline vs. participants from subgroups that did not use insulin at baseline. The EXAMINE and SAVOR-TIMI 53 studies were excluded from sensitivity analyses because DPP-IV inhibitor drugs did not show CV benefit in their individual trials.
Researchers calculated relative risk for all comparison groups based on the number of cases and noncases in each group.
“We reported RRs for four comparison groups to compare the associations between new diabetes medicine treatment with or without insulin usage and cardiovascular events,” the researchers wrote. “Four group sets were listed as the following: new drug treatment without baseline insulin vs. placebo without baseline insulin, new drug treatment with baseline insulin vs. new drug treatment without baseline insulin, new drug treatment with baseline insulin vs. placebo with baseline insulin, and placebo with baseline insulin vs. placebo without baseline insulin.”
In pooled analyses, researchers found that treatment with any new diabetes drug but without insulin for type 2 diabetes was associated with CV benefit compared with placebo with no insulin at baseline (pooled RR = 0.85; 95% CI, 0.77-0.95). However, for patients prescribed insulin at baseline, researchers still observed a significant benefit in CV risk reduction when assigned diabetes drugs, with an RR of 0.93 (95% CI, 0.88-0.98).
Adverse effects on CV outcomes were associated with baseline insulin treatment for participants in the drug treatment groups (RR = 1.52; 95% CI, 1.43-1.62) and the placebo groups (RR = 1.33; 95% CI, 1.16-1.52).
“Providers should encourage the use of SGLT2 inhibitors and GLP-1 receptor agonists more in diabetes regimens, regardless of whether patients are prescribed insulin,” Khatib said. “We need more clinical trials examining the cardiac benefits of SGLT2 inhibitors and GLP-1 agonists for patients prescribed insulin, but with more information on diabetes control and the extent of that benefit provided as the diabetes control is worse.”
For more information:
Joanna Khatib, MBBS, can be reached at joannaek89@gmail.com.
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