SAN FRANCISCO – A new meta-analysis suggests – but does not prove – that black patients with type 2 diabetes may not benefit from the widely heralded cardioprotective effects of the diabetes drugs classified as sodium-glucose transporter 2 inhibitors and glucagonlike peptide–1 receptor agonists.
Dr. Basem Mishriky
“Both are excellent classes of medications that improve hemoglobin A1c, reduce weight, and may have a renal-protective effect. But because there is no clear evidence of [their] cardiovascular benefit in [black] patients, it may remain appropriate to use other [drugs] when metformin fails,” said internist and lead study author Basem Mishriky, MD, of East Carolina University, Greenville, N.C. He spoke after the report was presented at the annual scientific sessions of the American Diabetes Association.
Dr. Mishriky cautioned that the findings of the analysis were not conclusive because the trials included in their analysis had a low number of black patients and were not powered to uncover racial differences.
Recent study results have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 receptor (GLP-1R) agonists have significant positive effects on cardiovascular risk. In a 2019 meta-analysis, researchers examined the results of eight trials with 60,082 participants and found that the risk of a composite measure of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular mortality fell by about 12% (SGLT2 inhibitors: hazard ratio, 0.86; 95% confidence interval, 0.74-1.01 and GLP-1R agonists: HR, 0.88, 95% CI, 0.78-0.98). The study was published in Diabetic Medicine (2019;36[4]:444-52).
Dr. Mishriky and his colleagues decided to conduct their analysis after noticing the high number of white patients included in the cardiac safety trials of these medications. “We cannot assume that a drug causes benefit in [black] patients just because it improved outcomes in a population that was predominantly white,” he said. “The onset of the traditional risk factors for cardiovascular disease, such as diabetes, obesity, and hypertension, occur at an earlier age in [black] patients, and there is a high prevalence of sickle cell trait in [black] patients, which is associated with increased risk for diabetes-related complications.”
In addition, some medications, such as angiotensin-converting enzyme inhibitors, may result in lower reductions in blood pressure in black patients, compared with their white counterparts, he noted.
For the new study, Dr. Mishriky and his colleagues included six cardiovascular safety trials of medications in the two classes of drugs (two for SGLT2 inhibitors and four for GLP-1R agonists) that reported statistically significant decreases in cardiovascular risk. The trials included a total of 53,978 patients, of whom 2,794 (5%) were black.
The researchers found no significant evidence of a difference in the incidence of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) between the diabetes medications (SGLT2 inhibitors or GLP-1R agonists) and placebo among black patients with type 2 diabetes and cardiovascular disease, Dr. Mishriky said.
When the two classes of drugs were pooled, the cardiovascular risk in patients who took the drugs, compared with those who received placebo, was statistically insignificant (risk ratio, 0.97; 95% CI, 0.68-1.39, P = .88). The risk was also statistically insignificant when the SGLT2 inhibitors and GLP-1R agonists were compared separately with placebo (RR, 1.00; 95% CI, 0.47-2.14; P = .99 and RR, 0.96; 95% CI, 0.61-1.53; P = .87; respectively). A comparison of the results for the SGLT2 inhibitors and the GLP-1R agonists showed no difference either.
Dr Mishriky said the results suggest that alternative medications to SGLT2 inhibitors and GLP-1R agonists, such as pioglitazone (Actos) and dipeptidyl peptidase–4 (DPP-4) inhibitors, might be considered for black patients who fail metformin.
He noted that, given the limitations of the trials included in the analysis, additional trials with SGLT2 inhibitors and GLP-1R agonists were needed to evaluate cardiovascular benefit in black patients.
An expanded version of the meta-analysis will be published soon, he added.
Dr Mishriky and his colleagues reported no relevant disclosures.
SOURCE: Mishriky B et al. ADA 2019, Abstract 242-OR.