The importance of treatment sequencing with SGLT2 inhibitors and GLP-1 receptor agonists combination for kidney function preservation in type 2 diabetes

Aims: To determine whether the sequence of initiation between sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) influences kidney outcomes in people with type 2 diabetes (T2D) receiving these therapies in association. Materials and methods: We retrospectively included adults with T2D treated with both a SGLT2i and a GLP-1RA, stratified by treatment sequence: SGLT2i followed by GLP-1RA or GLP-1RA followed by SGLT2i. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from initiation of the first drug. Analyses used mixed models for repeated measures adjusted with inverse probability of treatment weighting (IPTW) and confirmed by propensity score matching (PSM). Results: Among 565 participants (mean age 64 years, 29% women, diabetes duration 14 years, baseline eGFR 80 mL/min/1.73 m2), 210 initiated SGLT2i first and 355 GLP-1RA first. Over a median 4.3-year follow-up, eGFR declined more slowly in the SG group than in the GS group (adjusted difference 0.80 mL/min/1.73 m2 per year; 95% CI 0.23–1.37; p = 0.006); this effect was more evident in patients with CKD at baseline. PSM analyses yielded consistent results. Changes in urine albumin-to-creatinine ratio, HbA1c, and body weight were similar between groups. Conclusions: In people with T2D receiving combination therapy, initiating treatment with a SGLT2i was associated with greater long-term preservation of kidney function compared with starting with a GLP-1RA. Early SGLT2i use may confer better renal protection even when GLP-1RA intensification is subsequently required, confirming SGLT2i as a foundational therapy for preventing the decline in renal function in T2D.