PracticeUpdate: Conference Series | ADC 2018

Once-WeeklyDulaglutideNoninferior toOnce-Daily Liraglutide inPatientsWithType 2Diabetes Both GLP-1 receptor agonists showed strong antihyperglycemic effects, further confirming the benefits of this class of drugs for themanagement of T2D. BY THE PRACTICEUPDATE EDITORIAL TEAM

T he AWARD-6 study showed that glycemic control with once-weekly dulaglutide was not inferior to that with once-daily liraglutide in the management of type 2 diabetes (T2D). Both drugs produced robust HbA1c reductions in most patients, reaching the American Diabetes Association HbA1c target of <7.0%. Dulaglutide, a long-acting GLP-1 receptor agonist, is now available on the PBS in Australia. It has a longer plasma half-life than liraglutide and is given subcutaneously once a week. “The AWARD-6 study demonstrates strong anti- hyperglycemic profiles for both GLP-1 receptor agonists dulaglutide and liraglutide, further con- firming the benefits of this class for the treatment of type 2 diabetes,” said Tim Davis, MBBS, DPhil, FRCAP, MRCP, Professor of Medicine at the University of Western Australia, and Consultant Physician and Endocrinologist at Freemantle Hospital, in Western Australia. The AWARD-6 study compared the efficacy and safety of once-weekly dulaglutide 1.5 mg versus once-daily liraglutide 1.8 mg in 599 patients with T2D who were being treated with metformin ≥1500 mg. The primary objective of the study was to show non-inferiority in terms of glycemia (HbA1c) at 6 months compared with baseline, with a non-in- feriority margin of 0.4%. In this phase III, open-label, parallel-arm 26-week study, there was a short run-in period followed by randomization onto either the once-weekly dula- glutide or once-daily liraglutide groups. Patients in the liraglutide group underwent dose titration from 0.6 mg to 1.8 mg, usually within the first few weeks of the study, to help ensure that as many patients were on the full liraglutide dose as possible. Safety data were collected for a further 4 weeks following the main study. The baseline characteristics of patients in both groups were very similar: approximately a 50:50 female-to-male ratio, average age of 57 years, mean HbA1c of 8.1%, and mean body weight of 94.1 kg. The adjusted change from baseline at 26 weeks for a reduction in HbA1c was –1.42% in the dulaglu- tide group and –1.36% in the liraglutide group. The mean treatment difference in HbA1c was –0.06%

(95% CI, –0.19 to 0.07; P

< .0001) between

non-inferiority

the two groups. While both groups experienced significant weight reduction, liraglutide-treated patients demonstrated a 0.71-kg greater reduction than dulaglutide-treated patients (P = .01). " The adjusted change from baseline at 26 weeks for a reduction in HbA1c was –1.42% in the dulaglutide group and –1.36% in the liraglutide group. " As predicted for this class of drug, themost common treatment-related adverse events were gastroin- testinal-related. The most common adverse events for both dulaglutide and liraglutide included nau- sea (20.4% with dulaglutide, 18.0% with liraglutide), diarrhea (12.0%, 12.0%), dyspepsia (8.0%, 6.0%), and vomiting (7.0%, 8.3%). “With persistent dosing, nausea rates in both groups fell in the second half of the follow-up period to about 3–4%,” Dr. Davis said. Of the 299 patients randomized to dulaglutide and the 300 to liraglutide, 269 patients in each group finished treatment at week 26. The number of patients who discontinued the study and/or discontinued the assigned drug due to gastroin- testinal adverse events were similar (dulaglutide, 3.0%; liraglutide, 4.3%). “Retention in the study was excellent and there was no difference in the number of patients who withdrew from the study between both groups," Dr. Davis said. Meanwhile, the rate of hypoglycemia was 0.34 events per patient per year for dulaglutide and 0.52 for liraglutide. No severe hypoglycemia was reported in either group.

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ADC 2018 • PRACTICEUPDATE CONFERENCE SERIES