SGLT2 inhibitors are foundational for CKD/T2D, GLP-1 RAs as add-on for high cardiometabolic risk, expert consensus finds.
Background
The optimal positioning and sequencing of sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with chronic kidney disease (CKD), type 2 diabetes (T2D), and overweight/obesity remains unclear despite both classes demonstrating significant cardiorenal benefits. Current guidelines lack specific recommendations on when to prioritize or combine these agents, leaving clinicians without a clear framework for managing this complex patient population and maximizing therapeutic outcomes.
Study Design
An international Delphi panel, involving 114 participants from 10 countries, was conducted in two rounds to establish expert consensus. Statement development was informed by a systematic literature review and guided by 12 global experts. Consensus was predefined as ≥75% agreement or disagreement among panellists. The panel aimed to define the foundational versus adjunctive roles of SGLT2is and GLP-1 RAs in adults with CKD and T2D.
Results
Consensus was reached on 13/30 (43%) statements in Round 1 and 7/17 (41%) in Round 2. Panellists strongly agreed that SGLT2is should be considered foundational therapy for adults with CKD and T2D, irrespective of their body mass index (BMI). This highlights a primary role for SGLT2is in mitigating cardiorenal risk. Conversely, GLP-1 RAs achieved consensus as an add-on therapy, specifically for individuals with a BMI ≥35 kg/m2 who also present with significant cardiometabolic complications, such as persistent glycated haemoglobin A1c (HbA1c) elevation or established atherosclerotic cardiovascular disease.
Key Findings
- SGLT2 inhibitors are foundational therapy for CKD and T2D, independent of BMI.
- GLP-1 RAs are add-on therapy for BMI ≥35 kg/m2 with cardiometabolic complications (e.g., elevated HbA1c, ASCVD).
- Combination therapy with SGLT2is and GLP-1 RAs is appropriate for persistent CKD progression, high cardiovascular risk, or suboptimal metabolic control.
Why It Matters
This consensus provides a clearer, evidence-based framework for clinicians managing CKD and T2D patients, particularly those with overweight/obesity. SGLT2is are now firmly positioned as the foundational first-line therapy for cardiorenal protection, simplifying initial treatment decisions regardless of BMI. GLP-1 RAs are best integrated as an add-on for patients with higher BMI and existing cardiometabolic comorbidities, or in combination for those with ongoing kidney disease progression or high cardiovascular risk. This guidance helps optimize treatment sequencing and combination strategies, potentially improving patient outcomes in a complex disease landscape.
sglt2-inhibitor
glp-1-agonist
chronic-kidney-disease
type-2-diabetes
obesity
consensus