Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation.

OBJECTIVE: To compare the risk of renal deterioration under treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose contransporter-2 (SGLT-2) inhibitors versus other second line treatments in people with type 2 diabetes with and without albuminuria (albumin to creatinine ratio ≥30 mg/g). DESIGN: Target trial emulation. SETTINGS: Linkage of electronic health records and claims data from 10 health systems and two national health insurance plans-data from BESTMED (observational evaluation of second line therapy medications in diabetes) study. PARTICIPANTS: People with type 2 diabetes and moderate cardiovascular risk and estimated glomerular filtration rate ≥45 mL/min/1.73 m2 on metformin monotherapy who started treatment with a GLP-1 receptor agonist or SGLT-2 inhibitor, a sulfonylurea, or a dipeptidyl peptidase-4 (DPP-4) inhibitor after metformin between 2014 and 2022. MAIN OUTCOME MEASURE: Deterioration of kidney function defined as doubling of serum creatinine or estimated glomerular filtration rate <15 mL/min/1.73 m2. RESULTS: Among 75 455 eligible people (61 583 (81.76%) without albuminuria), median age was 60 years (interquartile range 51-68), 36 231 (48%) were women, median haemoglobin A1c was 7.8% (interquartile range 7.3-8.5%), and median estimated glomerular filtration rate was 92 mL/min/1.73 m2 (interquartile range 77-102). People were followed for a median of 32 months (interquartile range 18-57). The estimated five year risk of the renal outcome was 2.4% (95% confidence interval 2.1% to 2.7%) for people taking GLP-1 receptor agonists or SGLT-2 inhibitors versus 2.1% (1.8% to 2.6%) for people taking DPP-4 inhibitors among those without albuminuria; and 3.2% (2.3% to 4.1%) versus 5.4% (4.2% to 6.7%), respectively, among people with albuminuria. The estimated five year risk ratio comparing the GLP-1 receptor agonist or SGLT-2 inhibitor group with the DPP-4 inhibitor group was 1.10 (95% confidence interval 0.90 to 1.38) among people without albuminuria and 0.60 (0.42 to 0.82) among people with albuminuria. CONCLUSIONS: Compared with DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors reduce the risk of deterioration of renal function in people with albuminuria. Little evidence of renal benefit among people without albuminuria was observed over the study follow-up period.