Patients with type 2 diabetes achieved better glycemic control and gained less body weight with thrice-daily lispro combined with once-weekly dulaglutide than combined with nightly insulin glargine, according to research presented at the 50th European Association for the Study of Diabetes Annual Meeting.
“Dulaglutide, together with metformin or alone, and in combination with insulin lispro at mealtimes, is an effective and safe option for treatment intensification in patients with type 2 diabetes and those inadequately controlled on one or two doses of insulin,” said Johan Jendle, MD, PhD, of Orebro University in Sweden.
In the 52-week, parallel-arm, open-label phase 3 AWARD-4 trial, Jendle and colleagues randomly assigned 884 patients (mean age, 59.4 years; diabetes duration, 12.7 years; HbA1c, 8.5%; body weight, 91.1 kg; BMI, 32.5 kg/m2; total daily insulin dose, 56 U) to once-weekly dulaglutide 1.5 mg (n=295), dulaglutide 0.75 mg (n=293) or bedtime insulin glargine (n=296) titrated-to-target.
Patients included were already receiving one to two doses per day of insulin, whether basal, basal with prandial or premixed insulin, and some metformin. The number of patients completing treatment with dulaglutide 1.5 mg, dulaglutide 0.75 mg and insulin glargine decreased at 26 weeks and 52 weeks.
The researchers looked for HbA1c changes at 26 weeks to assess noninferiority (0.4% margin), then proceeded to assess superiority.
Dulaglutide 1.5 mg and dulaglutide 0.75 mg were superior to insulin glargine for HbA1c change from baseline at 26 and 52 weeks. Greater fasting serum glucose reduction was seen with insulin glargine than the dulaglutide doses.
At 26 weeks, the mean prandial insulin doses were 93 U for dulaglutide 1.5 mg, 97 U for dulaglutide 0.75 mg and 68 U for insulin glargine; the insulin glargine dose was 65 U. At 52 weeks, similar insulin doses were observed.
Body weight decreased with dulaglutide 1.5 mg (–0.35 kg) but increased with dulaglutide 0.75 mg (0.86 kg) and insulin glargine (2.89 kg) at 52 weeks.
The rate of documented symptomatic hypoglycemia (≤3.9 mmol/L) at 52 weeks was 31 events per patient/year for dulaglutide 1.5 mg, 35 events per patient/year for dulaglutide 0.75 mg and 39.9 events per patient/year for insulin glargine. Fewer severe hypoglycemic events were seen with dulaglutide 1.5 mg (n=11) and dulaglutide 0.75 mg (n=15) compared with insulin glargine (n=22).
Nausea, diarrhea and vomiting were observed more often with dulaglutide 1.5 mg and dulaglutide 0.75 mg than with insulin glargine.
For more information:
Jendle J. Abstract #42. Presented at: 50th EASD Annual Meeting; Sept. 16-19, 2014; Vienna.
Disclosure: The study was funded by Eli Lilly and Company. Jendle reports being an advisory board member and speaker for Eli Lilly and other pharmaceutical companies.