HDCN Abstract:  ASN Annual Meeting 2020 -- Digital Meeting  

Tuttle KR, Cherney D, Hadjadj S, et al.

Reduction in the Rate of eGFR Decline with Semaglutide vs. Placebo: A Post Hoc Pooled Analysis of SUSTAIN 6 and PIONEER 6

ASN Annual Meeting 2020 -- Digital Meeting
J Am Soc Nephrol (Oct) 31:36A 2020


The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated that once-weekly (OW) subcutaneous (s.c.) semaglutide may have beneficial effects on kidney function in subjects with type 2 diabetes (T2D) at high CV risk. SUSTAIN 6 and the PIONEER 6 CVOT (once-daily [OD] oral semaglutide) had similar designs and populations, and both evaluated the effects of semaglutide vs placebo (PBO) on macro- and microvascular outcomes. This post hoc analysis of pooled data from the two trials evaluated the effects of semaglutide vs PBO on kidney function decline.


Data for 6,480 subjects with T2D from SUSTAIN 6 (OW s.c. semaglutide 0.5 and 1.0 mg or PBO, N=3,297; median follow-up 2.1 years) and PIONEER 6 (OD oral semaglutide 14 mg or PBO, N=3,183; median follow-up 1.3 years) were pooled into two groups: semaglutide and PBO. Annual change in estimated glomerular filtration rate (eGFR) was compared (semaglutide vs PBO) in the overall population and subgroups by baseline (BL) eGFR (≥30–<60 or ≥60 mL/min/1.73 m2). Changes in eGFR from BL during trial were analyzed using a linear random regression model with individual intercept and time slope. The estimated treatment difference (ETD) at 1 year between annual rates of eGFR slope from BL was calculated; an interaction p-value <0.05 indicated difference between subgroups.


In the overall population, the annual rate of eGFR change was 0.60 mL/min/1.73 m2 (p<0.0001) lower with semaglutide vs PBO. In the eGFR ≥30–<60 mL/min/1.73 mand ≥60 subgroups, the ETDs for semaglutide vs PBO were, respectively, 1.07 and 0.48 mL/min/1.73 m2/year, with a non- significant interaction p-value (Figure).


Semaglutide was associated with a significantly smaller decline in kidney function than PBO in subjects with T2D at high CV risk across tested BL eGFR categories; the data suggest the main benefit might be observed in those with kidney disease.

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