Slide 1: One Year after FLOW and more from SOUL
One Year after FLOW and more from SOUL Title Presenter Oral Semaglutide and Kidney Outcomes in Type 2 Diabetes: A Prespecified Analysis of the SOUL Randomised Cardiovascular Johannes Mann Outcomes Trial Semaglutide for the treatment of type 2 diabetes and chronic kidney disease: The impact of mainta
Slide 2: Oral semaglutide and kidney outcomes in type 2 diabetes: SOUL analysis
Oral semaglutide and kidney outcomes in type 2 diabetes: a prespecified analysis of the SOUL randomised cardiovascular outcomes trial Johannes F. E. Mann, MD; N Marx, MD; JE Deanfield, MD; SS Emerson, MD, PhD; SE Inzucchi, MD; DK McGuire, MD, MHSc; SL Mulvagh, MD; R Pop-Busui, MD, PhD; NR Poulter, F
Slide 3: Conflicts of interest
Conflicts of interest Presenting author Johannes F. E. Mann reports: • Grants from Novo Nordisk, European Union and McMaster University Hamilton, Canada, AstraZeneca, Bayer, Boehringer, Hexal and Sanofi • Consulting fees from Novo Nordisk, AstraZeneca, Bayer and Boehringer Ingelheim • Personal fees/
Slide 4: Background
Background People with T2D are at high risk for CKD and kidney failure1 Once-weekly 1.0 mg injectable semaglutide improves kidney outcomes compared with placebo in people with T2D and CKD2 The effect of once-daily oral semaglutide on kidney outcomes in people with T2D + CVD and/or CKD is investigate
Slide 5: SOUL trial design
SOUL trial design1,2 3 mg 7 mg 14 mg oral semaglutide OD Screening Follow-up 3 mg 7 mg 14 mg placebo OD Week 0 Week 4 Week 8 5 weeks Treatment period (event-driven, ≥1225 first EAC-confirmed MACE) Estimated 5 years End-of-treatment Follow-up Randomisation (1:1) visit visit Key inclusion criteria End
Slide 6: Baseline characteristics
Baseline characteristics Mean HbA1C Median T2D Male/female (%) Mean age (years) Mean BMI (kg/m2) (% [mmol/mol]) duration (years) 71.1/28.9 66.1 8.0 (63.5) 31.1 14.7 Medical history Baseline characteristics and lab parameters CVD only 56.7% Blood pressure Systolic 134.6 (mmHg) Diastolic 76.7 CKD only
Slide 7: Primary CV outcome
Primary CV outcome Primary endpoint: 3-point MACE 20 Cumulative incidence (%) HR 0.86 (95% CI: 0.77; 0.96) p=0.006 for superiority (two-sided) 15 Placebo 10 Components: Oral semaglutide • CV-related death • Nonfatal MI 5 • Nonfatal stroke 0 0 6 12 18 24 30 36 42 48 54 60 Time since randomisation (mo
Slide 8: Individual components of the primary outcome
Individual components of the primary outcome Oral semaglutide Placebo Outcome HR (95% CI) No. of participants with event/ no. of participants in analysis MACE 579/4825 668/4825 0.86 (0.77; 0.96) CV death 301/4825 320/4825 0.93 (0.80; 1.09) Nonfatal MI 191/4825 253/4825 0.74 (0.61; 0.89) Nonfatal str
Slide 9: 5-point major kidney outcomes
5-point major kidney outcomes 14 Proportion of participants (%) HR 0.91, 95% CI: 0.80; 1.05, p=0.19 (two-sided) 12 Events: 403 (oral sema), 435 (placebo) Components: 10 Placebo • CV-related death 8 • Kidney-related death • Persistent ≥50% 6 Oral semaglutide eGFR reduction 4 • Persistent eGFR <15 mL/
Slide 10: 4-point composite kidney outcomes (excluding CV-related death)
4-point composite kidney outcomes (excluding CV-related death) 3.0 Proportion of participants (%) HR 0.86, 95% CI 0.66; 1.10 2.5 Events: 112 (oral sema), 129 (placebo) Placebo Components: 2.0 • Kidney-related death 1.5 Oral semaglutide • Persistent ≥50% eGFR reduction 1.0 • Persistent eGFR <15 mL/mi
Slide 11: Individual components of the composite kidney outcomes
Individual components of the composite kidney outcomes Oral Placebo Outcome semaglutide HR (95% CI) No. of participants with event/ no. of participants in analysis 5-point composite 403/4825 435/4825 0.91 (0.80; 1.05) 4-point composite 112/4825 129/4825 0.86 (0.66; 1.10) ≥50% eGFR loss 71/4781 86/47
Slide 12: Composite kidney outcomes in those with eGFR <60 at baseline
Composite kidney outcomes in those with eGFR <60 mL/min/1.73 m2 at baseline 5-point composite kidney outcome 4-point composite kidney outcome 20 7 HR 0.84, 95% CI 0.69; 1.02, p=0.08 HR 0.80, 95% CI 0.58; 1.09, p=0.16 Proportion of participants (%) Events: 185 (oral sema), 214 (placebo) 6 Events: 72
Slide 13: Mean eGFR over time in the overall population
Mean eGFR over time in the overall population 75 74 eGFR (mL/min/1.73m2) 73 72 70.5 71 Oral semaglutide 70 68.5 69 Annual rate of change in eGFR (mL/min/1.73m2) Placebo 68 Oral sema: –1.67, placebo: –2.06 ETD: 0.40 (95% CI 0.27; 0.53) 0 67 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Time since ra
Slide 14: Mean eGFR over time by baseline kidney function
Mean eGFR over time by baseline kidney function eGFR ≥60 mL/min/1.73m2 eGFR <60 mL/min/1.73m2 Annual rate of change in eGFR (mL/min/1.73m2) Annual rate of change in eGFR (mL/min/1.73m2) Oral sema: –1.93, placebo: –2.27 Oral sema: –1.04, placebo: –1.59 87 ETD: 0.34 (95% CI 0.19; 0.49) 48 ETD: 0.55 (9
Slide 15: Safety
Safety • SAEs were reported in 47.9% participants treated with oral semaglutide and 50.3% with placebo1 • Treatment with oral semaglutide vs placebo was not associated with an increased rate of: • Serious kidney adverse events (1.19 vs 1.45 per 100 person-years) • Acute kidney injury* (0.76 vs 0.93
Slide 16: In FLOW, superiority of semaglutide vs placebo was confirmed
In FLOW, superiority of semaglutide vs placebo was confirmed for the primary and 3 confirmatory secondary outcomes FLOW was a dedicated kidney outcomes trial of 1.0 mg injectable semaglutide vs placebo, in participants with T2D and CKD First composite kidney event Hierarchical testing HR: 0.76 [0.66
Slide 17: In SELECT, a significant decrease in risk of adverse kidney outcomes
In SELECT, a significant decrease in risk of adverse kidney outcomes was observed with semaglutide Time to first occurrence of the main 5-component kidney composite endpoint* 0.03 HR: 0.78, 95% CI 0.63; 0.96; p=0.02 Incidence: 1.8% (sema), 2.2% (placebo) Placebo SELECT was a dedicated Probability of
Slide 18: Conclusions
Conclusions Oral semaglutide in people with T2D at low kidney disease risk: • Numerically reduced the main 5-point kidney outcome (non-significant) • Numerically to a larger extend reduced the 4-point outcome (excluding CV death; non-significant) • Reduced the loss of eGFR (effect more pronounced wh
Slide 19: Thank you for your attention
Thank you for your attention Contact: Professor Johannes F. E. Mann prof.j.mann@gmail.com