Evidence-Based Positioning of Sodium-Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Receptor Agonists in the Management of Chronic Kidney Disease with Type 2 Diabetes and Overweight or Obesity: A Systematic Literature Review

Introduction Both sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have demonstrated kidney benefits in adults with chronic kidney disease (CKD) with type 2 diabetes (T2D) and overweight/obesity. However, questions remain regarding the optimal positioning, combination and sequencing of the two drug classes. This systematic literature review (SLR) identified evidence on comparisons, combinations or sequencing of SGLT2is and GLP-1 RAs in this population. Methods Databases were searched in May 2025. Relevant congresses between 2023 and 2025, SLR bibliographies and ClinicalTrials.gov were hand-searched. Articles were screened by two independent reviewers. Kidney and composite kidney outcomes were prioritised as the most clinically relevant for a population with CKD; additional safety, cardiovascular, HbA1c and weight endpoints were also extracted. Results Electronic databases identified 922 records, with an additional 117 records from hand searches. In total, 48 publications were included reporting on 38 unique studies; comprising 11 meta-analyses (MAs) and 27 primary publications. Findings from MAs consistently favoured SGLT2is over GLP-1 RAs for composite kidney outcomes. Primary research studies showed no clear direction of benefit for change in estimated glomerular filtration rate (eGFR) or albuminuria from baseline, or eGFR decline. However, progression of kidney disease, where reported, was consistently reduced with SGLT2is versus GLP-1 RAs. Conclusion In the absence of head-to-head trials, the evidence identified supports the use of SGLT2is as a foundational therapy in adults with CKD and T2D, offering kidney protection, metabolic and cardiovascular benefits, with GLP-1 RAs positioned as a complementary adjunct. PROSPERO ID CRD420251053598. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-026-03559-7.