From the Journals

Newer antihyperglycemic drugs have distinctive CV, kidney benefits



The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

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