GLP-1RAs and SGLT2is Reduce Cardiovascular Events Independent of Reductions of Systolic Blood Pressure and Body Weight: A Meta-Analysis with Meta-Regression

Mei Qiu; Liang-Liang Ding; Miao Zhang; Jin-Hao Lin; Xu-Bin Wei; Hua Huang

doi:10.1007/s13300-020-00912-z

GLP-1RAs and SGLT2is Reduce Cardiovascular Events Independent of Reductions of Systolic Blood Pressure and Body Weight: A Meta-Analysis with Meta-Regression

Diabetes Ther. 2020 Oct;11(10):2429-2440. doi: 10.1007/s13300-020-00912-z. Epub 2020 Aug 27.

Authors

Mei Qiu¹, Liang-Liang Ding², Miao Zhang³, Jin-Hao Lin⁴, Xu-Bin Wei⁵, Hua Huang⁶

Affiliations

¹ Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China. 13798214835@sina.cn.
² Department of Endocrinology, First Affiliated Hospital of Yangtze University, Jingzhou, 434000, China.
³ Department of Nephrology, Shenzhen Hospital of Beijing University of Chinese Medicine, Shenzhen, 518116, China.
⁴ Department of Gastroenterology, Shenzhen Hospital of Beijing University of Chinese Medicine, Shenzhen, 518116, China.
⁵ Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, China.
⁶ Department of Neurology, Hankou Hospital of Wuhan City, Wuhan, 430312, China.

Abstract

Introduction: The impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events during the treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is) for type 2 diabetes is unclear.

Methods: We searched Embase and PubMed. We performed meta-analysis using hazard ratio (HR) and 95% confidence interval (CI) as effect size stratified by drug class on six endpoints of interest, which were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), cardiovascular death (CVD), myocardial infarction (MI), stroke, and all-cause death (ACD). We performed meta-regression to assess the difference between GLP-1RAs and SGLT2is, and the impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events.

Results: We included 11 randomized trials. Compared with placebo, SGLT2is reduced HHF by 32% (HR 0.68, 95% CI 0.60-0.76) whereas GLP-1RAs reduced HHF by only 9% (HR 0.91, 95% CI 0.83-0.99). The benefit from SGLT2is on HHF was significantly greater than that from GLP-1RAs (P_subgroup = 0.004). GLP-1RAs reduced stroke by 16% (HR 0.84, 95% CI 0.76-0.93) whereas SGLT2is did not reduce stroke (HR 0.96, 95% CI 0.82-1.12). GLP-1RAs and SGLT2is similarly reduced MACE by 12%, CVD by 15%, MI by 9%, and ACD by 13%. The effects of systolic blood pressure reduction and body weight reduction on the logarithms of HRs of GLP-1RAs or SGLT2is vs. placebo as for reducing six endpoints of interest were not statistically significant (β ranged from - 0.145 to 0.269, and P ranged from 0.211 to 0.941).

Conclusions: GLP-1RAs and SGLT2is lead to similar benefits on MACE, CVD, MI, and ACD in adults with type 2 diabetes. The benefit from SGLT2is on HHF is greater than that from GLP-1RAs, while GLP-1RAs vs. placebo significantly reduce stroke whereas SGLT2is do not. The two drug classes reduce cardiovascular events independent of reductions of systolic blood pressure and body weight.

Keywords: Cardiovascular events; GLP-1RAs; SGLT2is; Type 2 diabetes.