Treatment with Exenatide Plus Insulin Glargine Associated with Decrease in Fasting Glucose and Body Weight

Combining the GLP-1 agonist exenatide with basal insulin glargine was associated with a decrease in fasting glucose and body weight, while insulin lispro combined with insulin glargine was associated with a slight increase in both measures, according to a study presented at this year’s annual scientific sessions of the American Diabetes Association in Chicago.

“The addition of meal-time prandial insulin is considered the gold standard when basal insulin is no longer sufficient control a patient’s diabetes, but it is associated with body weight gain and hypoglycemia, so we need an alternative,” said Michaela Diamant, MD, PhD, professor of internal medicine and chair of diabetology at Vrije Universiteit in Amsterdam, the Netherlands.

In the study, which was conducted at 108 sites in 17 countries, diabetic patients were randomized to two arms, with 247 receiving exenatide twice a day plus basal insulin, and 263 receiving lispro plus basal insulin glargine, according to abstract 70-OR, entitled “Exenatide BID vs. Insulin Lispro TIDM Added to Titrated Insulin Glargine QD in Metformin-Treated T2DM Patients Resulted in Similar Glycemic Control but Weight Loss and Less Hypoglycemia: The 4B Study.” (4B stands for "Basal insulin and exenatide BID compared to Basal insuline and Bolus insulin lispro in type 2 diabetes," Diamant said). At the end of the study, the median lispro dose was 0.5 intravenous kilograms per day, the abstract said.

Of 917 patients who entered the titration phase, 173 patients withdrew, according to Diamant. The remaining patients, who had had diabetes for a median of 13 years, had a median age of 60 and median body weight of 90 kilograms, according to the abstract. To participate, a patient had to have an HbA1c level greater than 7 percent but smaller than 10 percent, Diamant said.

In the exenatide arm, 17 patients withdrew, compared to 8 patients in the lispro arm, she said.

The primary objective was non-inferiority in the change in HbA1c level at 30 weeks from initiation. At the end of the study, blood glucose decreased similarly to 7.2 percent in both groups, with a p value of 0.001, according to the abstract.

However, being in the exenatide arm was associated with a lower fasting glucose and weight. For those in the exenatide arm, fasting blood glucose decreased by 0.4 millimoles, while it increased by 0.2 millimoles for those in the lispro arm, Diamant said. That measure had a p value of less than 0.002, according to the abstract.

Those in the exenatide group also lost an average of 2.5 kilograms, compared to a net gain of 2.1 kilograms for those in the lispro group, Diamant said.

Those in the exenatide arm also experienced less non-nocturnal hypoglycemia than those on lispro. The exenatide group had 0.6 non-nocturnal hypoglycemia compared to 3.3 events per year for those on lispro. Regarding nocturnal nocturnal hypoglycemia, however, the rates were almost the same, 1.5 for those in the exenatide arm, compared to 1.8 for the lispro arm, the abstract said.

However, 32 percent of patients in the exenatide group experienced nausea compared to 2 percent of those on lispro. For those in the exenatide group, 12 percent experienced vomiting, compared to 1 percent of those on lispro; and 11 percent of those on exenatide experienced diarrhea, compared to 5 percent of those on lispro, the abstract said.

“We need more pragmatic studies, in which we compare the current gold standard to something new," Diamant explained. "In the case of adding a GLP-1 receptor agonist, I would like to have a longer term study that would last for a couple of years, in order o see whether patients can delay the complex insulin treatment."