A new study has found that combining the drug pioglitazone with exenatide, in the form of AstraZeneca’s bydureon therapy, provides better blood sugar control in type 2 diabetes than insulin alone and helps promote weight loss.
Exenatide is part of a class of drugs called incretin mimetics, which improve blood sugar control by mimicking the action of a hormone called glucagon-like peptide 1 (GLP-1). It can also help with weight loss.
In this new randomised controlled trial, researchers at the University of Texas Health Science Centre at San Antonio compared the effectiveness of exenatide combined with pioglitazone versus insulin in terms of blood glucose control and weight loss.
A total of 231 adults with long standing, poorly controlled type 2 diabetes (elevated HbA1c and susceptible to hyperglycemia) taking metformin plus a sulphonylurea were given either the exenatide and pioglitazone combo or basal and prandial insulin for 18 months.
At six months, the 101 participants in the exenatide and pioglitazone treated group saw their HbA1c levels fall from a mean of 58 mmol/mol, at baseline among all participants, to 49.7 mmol/mol, as opposed to 57.4 mmol/mol in insulin-treated participants.
After a year, researchers found that the HbA1c levels of those treated with the exenatide combo decreased to 43 mmol/mol, compared with 54 mmol/mol in participants receiving the insulin therapy.
Researchers noted that it takes longer for the combination therapy to take effect. It wasn’t until the third month that the reductions in HbA1c became greater than those seen with insulin.
The rate of occurrence of hypoglycemia in the insulin group was over twice as high (5.8 vs. 2.1 events per patient per year) as what was recorded with the exenatide combination therapy. No severe hypoglycemia occurred in either group.
In addition to that, the six-month follow-up revealed that those in the insulin group gained substantially more weight than their peers taking exenatide with pioglitazone. Here, participants on insulin saw a 5.3 kg increase in weight, while the others only gained 2.7 extra kilos by the end of the study.
While the exenatide and pioglitazone combination therapy shows promise to lower blood sugar and limit weight gain in this study, information is thin on the ground when it comes to the safety of this particular combination.
There is evidence of side effects, such as nausea, vomiting and diarrhea, as well as changes to kidney function in some studies on exenatide use. Further research needs to be done to determine whether the same can be said of the combination therapy.

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