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

AbstractObjectiveTo 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).DesignTarget trial emulation.SettingsLinkage 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.ParticipantsPeople 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 measureDeterioration of kidney function defined as doubling of serum creatinine or estimated glomerular filtration rate <15 mL/min/1.73 m2.ResultsAmong 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.ConclusionsCompared 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.