Kidney Week

Abstract: PO0984

The Importance of Addressing Multiple Risk Markers in Type 2 Diabetes: Results from the LEADER Trial

Session Information

• Diabetic Kidney Disease: Clinical - 1
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Hein Zobel, Emilie, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Emilie Hein Zobel,

• Hansen, Tine, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Tine Hansen,

• Persson, Frederik, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Frederik Persson,

• Rasmussen, Soren, Novo Nordisk A/S, Søborg, Denmark

Soren Rasmussen,

• Von Scholten, Bernt Johan, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Bernt Johan Von Scholten,

• Wolthers, Benjamin, Novo Nordisk A/S, Søborg, Denmark

Benjamin Wolthers,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

Background

The benefit of multifactorial intervention in type 2 diabetes (T2D) was demonstrated in the small Steno-2 study in microalbuminuric T2D. Larger studies in more diverse cohorts are limited. We investigated the importance of multiple risk-marker improvement for micro- and macrovascular outcomes in the LEADER trial.

Methods

LEADER (n=9340, ClinicalTrials.gov number NCT01179048) randomized patients with T2D to liraglutide or placebo (1:1) in addition to standard of care. We categorized patients according to number of risk markers with a clinically relevant change at year 1 of treatment and investigated subsequent risk of an expanded cardiovascular outcome (MACE-6) or nephropathy. We defined clinically relevant change as: body weight loss ≥5%, HbA_1c reduction ≥1%, systolic blood pressure reduction ≥5 mmHg, LDL reduction ≥0.5 mmol/L, eGFR reduction ≥0 ml/min/1.73m² and urinary albumin-to-creatinine ratio reduction ≥30% of baseline value. Numbers of risk markers with change were classified as: none (group G0), 1 (G1), 2 (G2), 3 (G3) and ≥4 (G4). Cox regression analyzed risk of the outcomes adjusted for continuous baseline levels of the risk markers and treatment group.

Results

Compared to patients with no risk-marker change, risk of cardiovascular disease was lower for patients with 2 (HR [95% CI] 0.81 [0.66–0.98] or 3 (0.80 [0.65–0.99]) risk-marker changes, and risk of nephropathy was lower for those with 3 (0.50 [0.35–0.72]) or ≥4 (0.48 [0.31–0.73]) risk-marker changes (Table). Test for trend with number of improved risk markers as a continuous variable: p=0.004 and p<0.001, respectively.

Conclusion

Improvement in multiple risk markers within 1 year translates into reduced risk of micro- and macrovascular outcomes in T2D, underscoring the benefit of pleiotropic antidiabetic treatments.

Funding

• Commercial Support –