PracticeUpdate: Conference Series | ADC 2018

Adding Liraglutide to Standard of Care Lowers Risk of Glycemic Deterioration in T2D Patients at High CV Risk Liraglutide-treated patients also experienced greater reductions inHbA1c thanpatients receiving just standard of care, despite the use of other antihyperglycemic drugs in the control group. BY THE PRACTICEUPDATE EDITORIAL TEAM A post hoc analysis of the LEADER trial has found that patients with advanced type 2 diabetes (T2D) at high risk of cardiovas- cular disease benefitted from having liraglutide added to their standard of care. These patients had reduced risk of glycemic deterioration and hypoglycemia, and they experienced greater reductions in HbA1c compared with those who received placebo plus standard of care, despite greater intensification of treatment in the placebo group. The LEADER trial (n=9340) compared CV outcomes with the GLP-1 liraglutide versus placebo when added to standard of care in patients with T2D at high CV risk. Anthony Roberts, MBBS, FRACP, Endocrinologist at the Royal Adelaide Hospital in Adelaide, South Australia, presented results of the post hoc analysis of the LEADER trial at ADC 2018. The analysis assessed the long-term (up to 5 years) glycemic durability with liraglutide. “Despite the liraglutide and placebo groups following standard of care treatment guidelines, glycemic deterioration was evident in both groups,” Dr. Roberts said. However, liraglutide-treated patients declined more slowly compared with patients on placebo over the 5-year study follow-up: 69% versus 85%, respectively (HR, 0.50; 95% CI, 0.48–0.53; P < .001). HbA1c was reduced from baseline in both groups of patients, but reduction was greater with liraglutide. Three years into the study, the estimated treatment difference was –40% (95% CI, –45 to –0.34), despite the intensification of treatment in standard of care–alone group. Liraglutide-treated patients also experienced reduced hypoglycemia. Dr. Roberts, however, said that, while the results were encouraging, they should be viewed within the context of the study. “This was a post hoc analysis and the results may not be generalizable beyond the population recruited, that is patients with type 2 diabetes and at high risk of cardiovascular events.” In the study, baseline patient characteristics were evenly matched between the liraglutide (n=4668) and standard of care–alone (n=4672) groups: mean age, 64 years; diabetes duration, 12.8 years; HbA1c, 8.7%; and 45% were treated with insulin. Dr. Roberts and colleagues used Fine and Gray's proportional sub- hazards model to analyze treatment group differences in time to glycemic deterioration, defined as a composite of HbA1c ≥8.0% and reduction <0.5% since previous visit, or an increase in insulin or oral anti-hyperglycemic drug. They also analyzed individual components of the composite endpoint.

There was heterogeneity across countries for most outcomes, but these were directionally consistent across country and patient subgroups, including those with and without prior CVD. “The implications of the study are twofold. Firstly, the benefits seen in clinical trials for people with type 2 diabetes with prior cardiovascular disease also seem to be present in ordinary clinical practice,” Dr. Shaw said. “Secondly, it would appear that these benefits are a class effect, and may also extend to those people without prior CVD, although this requires confirmation in clinical trials.” The proportion of exposure time among patients in the SGLT2 inhibitor group was 75% to dapagliflozin, 9% to empagliflozin and 16% to other SGLT2 inhibitors. Dr. Shaw acknowledged that CVD-REAL 2 had a num- ber of limitations, including: ƒ ƒ There is the possibility of residual, unmeasured confounding, despite robust statistical techniques. ƒ ƒ Mortality data were available only from the inpatient setting in Japan and Singapore, where most fatal events occur in the hospital. However, sensitivity analyses excluding data from these two countries produced similar results. ƒ ƒ Safety endpoints were not examined. ƒ ƒ Experience with SGLT-2 inhibitors in the real world is relatively short, and longer-term follow-up is required to assess if the CV risks are sustained over time.

www.practiceupdate.com/c/73019

www.practiceupdate.com/c/73011

ADC 2018 • PRACTICEUPDATE CONFERENCE SERIES 15