Simulated head-to-head comparison of SGLT-2 inhibitors and GLP-1R agonists in type 2 diabetes

Head-to-head clinical trials comparing sodium-glucose transport protein 2 (SGLT-2) inhibitors to glucagon-like peptide-1 receptor (GLP-1R) agonists for kidney protection in patients with type 2 diabetes are not available. An observational study showed a slight improvement in acute kidney injury but also slightly increased mortality rates following SGLT-2 inhibitor treatment compared with GLP-1R agonists.

Adverse kidney outcomes are frequent complications in diabetes mellitus type 2 and are currently treated with SGLT-2 inhibitors or GLP-1R agonists. So far, clinical trials comparing the kidney protective effects of these two agents are however lacking. Dr Uffe Heide-Jørgensen (Aarhus University, Aarhus, Denmark) and team emulated a clinical trial from nationwide Danish population-based registries registry data. Trial participants included were adults with type 2 diabetes, an eGFR ≥30 mL/min/1.73 m² and a urine albumin-creatinine ratio <300 mg/g. Treatment consisted of SGLT2 inhibitors or GLP-1R agonists starting in January 2014 to November 2020. Participants with chronic kidney dialysis, kidney failure or transplant were excluded from the analysis. To address potential confounders arising from the lack of randomisation, the stabilised inverse probability of the treatment weighting method was used. The primary outcome was acute kidney injury estimated from laboratory measurements. A total of 36331 participants receiving SGLT2 inhibitors and 18822 participants receiving GLP-1R agonists were included.

Using an intention-to-treat analysis, there was an approximately 20% lower ratio of acute kidney injury events with SGLT2 inhibitors compared with GLP-1R agonists after 1 year of treatment (95% CI 0.74–0.90), This trend continued at 3 years and 5 years of treatment. The results were consistent favouring SGLT2 inhibitors in subgroups characterised by sex, age (<65 vs ≥65 years), albumin-creatinine ratio, and presence of cardiovascular disease. As an exception, no differences between treatment regimens were observed in the subgroup of participants with an eGFR < 60 mL/min/1.73 m^2. Numerically, the mortality rate was higher in participants receiving SGLT2 inhibitors compared with GLP-1R agonists (ratio 1.05; 95% CI 0.99–1.09).

“SGLT2 inhibitors are associated with a slightly higher mortality compared with GLP-1R agonists, but with somewhat lower rates of acute kidney injury”, said Dr Uffe Heide-Jørgensen (Aarhus University, Aarhus, Denmark). “The lower incidence of acute kidney injury was largely consistent across subgroups.”

1. Jensen SK, et al. Initiation of SGLT2i vs GLP1-RA and incidence of AKI in persons with type 2 diabetes mellitus. Abstract #462, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

Copyright ©2024 Medicom Medical Publishers



Posted on 20 June 202424 June 2024