Semaglutide treatment and renal function in the SUSTAIN 6 trial

Background:

Semaglutide is a GLP1-RA for treatment of T2D. SUSTAIN 6 was a 2year CVOT conducted in subjects with T2D at high risk for CV events. The results showed that semaglutide-treated subjects had a significant 26% lower risk of major adverse CV events vs. those receiving placebo. This post hoc analysis assessed the effect of semaglutide on renal function and renal AE by baseline estimated glomerular filtration rate in SUSTAIN 6. Materials: Changes in renal function, UACR and acute renal AEs were assessed in subjects categorised by baseline eGFR (mL/min/1.73 m2: normal ≥90, mild impairment < 90, moderate impairment < 60 and severe impairment < 30).

Results:

Mean eGFR decreased from baseline to week 104 across all treatment groups. The largest decreases were in subjects with normal renal function: –8.6 vs. –6.5 mL/min/1.73 m2 with semaglutide 1.0 mg vs. placebo, respectively. The corresponding changes in eGFR from baseline were –3.2 vs. –5.6 mL/min/1.73 m2 for subjects with mild-; –2.4 vs. –4.2 mL/min/1.73 m2 for subjects with moderate-; and –0.5 vs. –2.6 mL/min/1.73 m2 for subjects with severe renal impairment. UACR decreased with increasing renal impairment with semaglutide 1.0 mg, but not with other treatment groups. The number of AEs related to acute renal failure was generally higher in subjects with greater renal impairment at baseline. The proportion of subjects experiencing new or worsening nephropathy was lower with both semaglutide doses vs. placebo.

Conclusion:

No renal-related safety issues were observed with semaglutide regardless of baseline renal function.