Semaglutide Associated With Improved Kidney Function in Type 2 Diabetes

A post-hoc analysis of the SUSTAIN 1-7 clinical trials examined the effects of once-weekly subcutaneous semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, 0.5 mg and 1.0 mg compared with active treatments and placebo on kidney function and safety.

The clinical trials, published online in The Lancet Diabetes & Endocrinology, specifically assessed estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR), which are 2 key markers for chronic kidney disease, as well as other kidney adverse events (AEs). The SUSTAIN 1-5 trials, as well as the SUSTAIN 7 trial, were randomized controlled trials (RCTs); SUSTAIN 6 was the cardiovascular outcomes trial.

Individuals with type 2 diabetes are at an increased risk of chronic kidney disease, which can lead to kidney failure. Intensive glycemic control aids in reducing the risk of early onset complications, including kidney disease, compared with therapy that is less intensive.

Investigators combined data from the SUSTAIN 1-7 trials to offer clinicians a strong dataset to assess semaglutide on kidney function.

The collective data included 8417 patients with type 2 diabetes, aged 18 years or older. Patients were treated with a fixed dose-escalation regimen of once-weekly subcutaneous semaglutide, with dose increases occurring every 4 weeks, to achieve a maintenance dose of either 0.5 mg or 1.0 mg.

The number of participants and trial durations varied depending on the trial; SUSTAIN 1-5 and 7 were carried out with 388 to 1231 patients over a 30- to 36-week time frame, and SUSTAIN 6 included 3297 patients receiving semaglutide over 104 weeks. Comparators also varied: SUSTAIN 1, 5, and 6 compared against placebo; SUSTAIN 2 compared against sitagliptin; SUSTAIN 3 exenatide extended release; SUSTAIN 4 insulin glargine; and SUSTAIN 7 dulaglutide.

In SUSTAIN 1-5 and SUSTAIN 7, eGFR reductions between baseline to week 12 and baseline to week 30 in patients who received semaglutide 0.5 mg or 1.0 mg were greater than placebo group; the post-hoc analysis therefore reported an initial decline in eGFR up to approximately 12 weeks with semaglutide, followed by a plateau up to week 30. Overall, results from the trials demonstrated a decrease in eGFR with the drug compared with placebo, according to investigators.

The study additionally saw reductions in UACR across the SUSTAIN 1-6 trials with semaglutide treatment and active comparators; UACR increased in placebo groups. Analyses showed consistently lower UACR with semaglutide versus placebo.

Active comparators included in the study displayed similar results to semaglutide for eGFR and UACR over time.

Investigators expressed that a key limitation of the post-hoc analysis is the data’s heterogeneity, as SUSTAIN 1-5 and SUSTAIN 7 data were pooled despite differences in trial design.

Overall, results from this post-hoc analysis of data from the SUSTAIN 1–7 trials suggests that semaglutide has the potential to improve kidney outcomes with long-term treatment. “Long-term data from FLOW (NCT03819153)—to our knowledge, the first kidney outcomes trial with a GLP-1 receptor agonist—will be key to strengthening this hypothesis,” study authors wrote.

Reference:

1. Mann J, Hanson T, Idorn T, et al. Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomized controlled trials. The Lancet; 2020. doi: https://doi.org/10.1016/S2213-8587(20)30313-2.