The importance of addressing multiple risk markers in type 2 diabetes: results from LEADER and SUSTAIN 6

Presented at the EASD 2021 by: Frederik Persson, MD - Copenhagen, Denmark

Introduction and methods

This analysis investigated to which extend improvements of multiple risk markers affect outcomes in patients with T2DM in the LEADER and SUSTAIN 6 trials.

LEADER (n=8638; median follow-up 3.8 years) compared the effects of liraglutide vs placebo

and SUSTAIN 6 (n=3040; median follow-up 2.1 years) compared the effects of semaglutide vs placebo on outcomes in patients with T2DM aged ≥50 years and with established CVD or ≥60 years with CV risk factors. This post-hoc analysis pooled the liraglutide/semaglutide- and placebo-treated groups of both trials (total n=11678). Patients were categorized by the number of risk markers with clinically relevant improvements after 1 year (0 [reference group], 1, 2, 3 and ≥4 risk marker changes). Clinically relevant risk marker improvements were defined as body weight reduction ≥5%, HbA1c reduction ≥1%, SBP reduction ≥5 mmHg, LDL-c reduction ≥0.5 mmol/L, eGFR increase ≥0 mL/min/1.73m² and UACR reduction ≥30% of baseline value.

Outcomes investigated from year 1 onwards were MACE (CV death, nonfatal MI and stroke), expanded MACE (MACE, coronary revascularization or hospitalization for unstable angina pectoris or HF), CV death, and nephropathy (new onset macroalbuminuria, doubling of serum creatinine and eGFR ≤ 45 mL/min/1.73m², continuous renal replacement therapy or renal death).

Main results

• There was no significant difference in MACE between patients with 0, 1, 2, 3, or ≥4 improved risk makers.
• Compared with patients with 0 risk marker improvements, patients with 2, 3 or ≥4 improved risk markers had reduced risk of expanded MACE (HR 0.80, 95%CI 0.67-0.96, P=0.02; HR 0.80, 95%CI 0.66-0.97, P=0.02; and HR 0.82, 95%CI 0.66-1.02, respectively), CV death (HR 0.66, 95%CI 0.45-0.96, P=0.03; HR 0.67, 95%CI 0.45-0.99, P=0.04; and HR 0.60, 95%CI 0.38-0.94, P=0.03, respectively) and nephropathy (HR 0.71, 95%CI 0.52-0.97, P=0.03; HR 0.48, 95%CI 0.34-0.68, P<0.0001; and HR 0.43, 95%CI 0.29-0.65, P<0.0001, respectively).
• A trend of reduced risk with each additional risk marker improvement was observed for expanded MACE (P=0.004), CV death (P=0.005) and nephropathy (P<0.0001).

Conclusion

This post-hoc analysis of LEADER and SUSTAIN 6 showed that improvements in 2 or more risk markers were associated with reduced risk of expanded MACE, CV death and nephropathy as compared with 0 or 1 improved risk marker in patients with T2DM with established CVD or CV risk factors.

Frederik Persson stated that these findings underscore the importance of multifactorial intervention in patients with T2DM.

-Our reporting is based on the information provided at the EASD Virtual Meeting–