Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis

Chuanjun Zhuo; Chongguang Lin; Chunhua Zhou; Xiangyang Gao; Hailin Shao; Tao Fang; Hongjun Tian; Li Ding; Ming Liu

doi:10.3389/fphar.2021.759262

Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis

Front Pharmacol. 2021 Dec 24:12:759262. doi: 10.3389/fphar.2021.759262. eCollection 2021.

Authors

Chuanjun Zhuo^{1

2

3

4}, Chongguang Lin⁴, Chunhua Zhou⁵, Xiangyang Gao⁶, Hailin Shao¹, Tao Fang¹, Hongjun Tian¹, Li Ding², Ming Liu²

Affiliations

¹ National of Metabolism Management Center (MMC), Tianjin Medical University Affiliated Tianjin Fourth Center Hospital, Nankai University Affiliated Hospital, Tianjin Fourth Center Hospital, Tianjin, China.
² Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
³ Department of Psychiatric-Neuroimaging-Genetics Laboratory (PNGC_Lab), Tianjin Mental Health Center, Tianjin Medical University, Tianjin, China.
⁴ Department of Psychiatry, Wenzhou Seventh Peoples Hospital, Wenzhou, China.
⁵ Department of Pharmacy, The First Hospital of Hebei Medical University, Shijiazhuang, China.
⁶ Big Data Analysis Center of Health Management Institute, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

Abstract

Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy. Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo. Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

Keywords: cardio-renal benefit; glucagon-like peptide-1 receptor agonist; network meta-analysis; semaglutide; type 2 diabetes.