SGLT-2 Inhibitors, GLP1-RAs Show Cardiorenal Event Prevention
The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.
Key Takeaways
Among three classes of newer antidiabetic drugs, sodium glucose cotransporter-2 (SGLT-2) inhibitors were the most effective for reducing cardiovascular deaths, renal events, and hospitalizations for heart failure (HHF) in patients with or without diabetes.
Both SGLT-2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduced major adverse cardiovascular events (MACE).
Compared with placebo, SGLT-2 inhibitors were associated with a robust reduction of HHF and renal outcome, and a moderate reduction of cardiovascular and total death, and MACE.
The findings confirm that GLP-1RAs compared with placebo reduce the risk of MACE, total death, HHF, and a composite of adverse renal outcomes.
Dipeptidyl peptidase-4 (DPP-4) inhibitors did not work as well as SGLT-2 inhibitors or GLP-1RAs for preventing cardiovascular and renal disease.
Why This Matters
This meta-analysis included data from the most recently published cardiovascular outcome trials and hence provides the most up-to-date assessment of available evidence for cardiorenal outcomes produced by DPP-4 inhibitors, GLP-1RAs and SGLT-2 inhibitors, the authors said.
The findings confirmed the lack of any benefit from DPP-4 inhibitors on cardiorenal outcomes in people with type 2 diabetes.
SGLT-2 inhibitors and GLP-1RAs are the preferred treatments, after metformin, for patients with type 2 diabetes and cardiorenal disease.
Study Design
This study was a meta-analysis of 23 prospective, double-blind outcome trials that had at least 6-month follow-up and compared the efficacy of DPP-4 inhibitors, GLP-1RAs, or SGLT-2 inhibitors with placebo for preventing cardiovascular, heart failure, or renal outcomes in adult patients with or without type 2 diabetes.
Study participants were all adults, and all included trials were multinational, industry sponsored, had their results appear between 2013 and 2021, and their mean duration ranged from 9 months to 5.4 years. Enrollment in each trial ranged from 1222 to 17,160 patients, and together the 23 trials included 181,143 patients.
Four of the trials compared DPP-4 inhibitors with placebo in 43,522 patients, 8 trials compared GLP-1RAs with placebo in 60,080 patients, and 11 trials compared SGLT-2 inhibitors with placebo in 77,541 patients,
The primary outcome in each trial was MACE, a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), and nonfatal stroke. Cardiovascular and total death were coprimary outcomes. Nonfatal MI, nonfatal stroke, hospitalization for HF, and renal composite outcome were secondary outcomes.
Key Results
For the primary outcome of MACE, GLP-1RAs reduced the risk by a significant 13% compared with placebo, and SGLT-2 inhibitors reduced the risk by a significant 11% compared with placebo. Agents from each of these two drug classes showed no significant difference in their effects on MACE when compared, but each class significantly reduced MACE compared with DPP-4 inhibitors. The DPP-4 inhibitors showed no significant difference from placebo in their effect on MACE.
For the outcome of cardiovascular death, SGLT-2 inhibitors were associated with a significantly lower risk compared with placebo and with DPP-4 inhibitors. The effect of GLP1-RAs was not significantly different from the DPP-4 inhibitors or placebo and was not significantly different from the SGLT-2 inhibitors. SGLT-2 inhibitors and the GLP1-RAs did not differ significantly for this outcome, and the DPP-4 inhibitors did not significantly differ from placebo.
For the outcome of total death, the GLP1-RAs and SGLT2 inhibitors were each associated with a significantly lower risk compared with placebo and with DPP-4 inhibitors. The SGLT-2 inhibitors and the GLP1-RAs did not differ significantly for this outcome, and the DPP-4 inhibitors did not significantly differ from placebo.
For the outcome of HHF, the GLP-1RAs and SGLT-2 inhibitors were each associated with a significantly lower risk compared with placebo, and compared with the DPP-4 inhibitors, which were no better than placebo. The SGLT-2 inhibitors were also significantly better than the GLP1-RAs.
For renal outcomes, the GLP-1RAs and SGLT-2 inhibitors were each associated with a significantly lower risk compared with placebo, and compared with the DPP-4 inhibitors, which were no better than placebo. The SGLT-2 inhibitors were also significantly better than the GLP1-RAs.
Limitations
None of the cardiovascular outcome trials compared the drugs directly. The between-class comparisons depended on indirect evidence.
The analysis did not account for possible between-drug differences among agents within a class.
No patient-level data were available, making adjustment for potential confounders difficult.
Trial designs, patient characteristics, definitions of endpoints, and background therapies differed among the included studies.
Disclosures
The study received no funding.
Dario Giugliano, MD, received honoraria from Novartis, Sanofi, Eli Lilly, AstraZeneca, and Novo Nordisk.
Maria Ida Maiorino, MD, PhD, received honoraria from AstraZeneca, Bruno Farmaceutici, Mundipharma, Novo Nordisk, and Sanofi.
Katherine Esposito, MD, PhD, received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, and sanofi-aventis.
None of the other authors had relevant disclosures.
This is a summary of a preprint research study, “The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta- analysis of 23 CVOTs,” written by a research team located primarily at the University of Campania Luigi Vanvitelli, Naples, Italy, on Research Square, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.
For more news, follow Medscape on Facebook, Twitter, Instagram, YouTube, and LinkedIn
Source: Read Full Article