Sustained glycaemic control, lower amputation risk with liraglutide
Adding liraglutide treatment to standard of care (SoC) reduced the risk of worsening glycaemic control, along with greater reductions in HbA1c levels in patients with type 2 diabetes (T2D) compared with SoC alone, according to long-term data of the LEADER trial presented at IDF 2017. Risk of amputation also appeared to be lower in liraglutide-treated patients with diabetic foot ulcer (DFU).
Patients with T2D (mean age 64 years, diabetes duration 12.8 years) who were randomized to liraglutide (n=4,668) or placebo (n=4,672), in addition to SoC, for a duration of up to 5 years were assessed for time to glycaemic deterioration ─ defined as a combined endpoint of HbA1c ≥8.0 percent and a reduction of <0.5 percent since the last visit, or increased use of insulin/oral antihyperglycaemic drug (OAD) including initiation of OAD or insulin use, insulin dose increase by ≥10 units, or addition of fast-acting/mixed insulin to basal insulin. [IDF 2017, abstract OP-0014]
After adjusting for all-cause mortality, risk of glycaemic deterioration was lower in the liraglutide vs the placebo groups. Fewer patients in the liraglutide than the placebo groups (69 percent vs 85 percent) were estimated to have worsening glycaemic control over 5 years based on the Fine and Gray’s proportional subhazards model.
Individual components of the composite glycaemic deterioration endpoint were also less likely to occur with liraglutide than with placebo.
At 3 years, HbA1c reduction from baseline was greater with liraglutide than with placebo (mean change, -1.16 percent vs -0.77 percent, estimated treatment difference, -0.40 percent, 95 percent confidence interval, -0.45 to -0.34). This occurred despite patients in the placebo group increased their use of antihyperglycaemic medications.
In addition, fewer hypoglycaemic episodes occurred in the liraglutide vs the placebo groups, who received SoC alone.
Potential risk reduction for amputation in diabetic foot ulcer
A post hoc analysis of the LEADER trial showed that DFU occurred in similar proportions of patients in both the liraglutide and the placebo groups (proportion reporting ≥1 DFU episode, 3.9 percent vs 4.2 percent, hazard ratio [HR], 0.91; p=0.38). [IDF 2017, P-0694]
Among the patients who developed DFU during the study, similar proportions reported DFU complications, including infections (60.8 percent vs 68.6 percent; p=0.12), peripheral revascularization (11.4 percent vs 12.0 percent; p=0.84), and involvement of underlying structures (36.4 percent vs 41.9 percent; p=0.28) in both treatment groups.
However, liraglutide-treated patients had lower amputation rates than the placebo group (25.0 percent vs 35.1 percent; p=0.04). Also, a lower proportion of subjects with DFU needed amputation of the foot, lower leg or leg in the liraglutide group compared with the placebo group (7.4 percent vs 15.7 percent; p=0.01).
“These findings may suggest a reduced risk of amputation in those with DFU when treated with liraglutide vs placebo in patients with T2D and increased risk of CV events,” said lead author Dr Ketan Dhatariya of the Norfolk and Norwich University Hospitals NHS Foundation Trust in Norwich, UK.