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LISBON -- Combining titrated insulin glargine with once-weekly exenatide helped patients achieve both weight loss and hemoglobin A1c improvement, researchers reported here.

In a post-hoc analysis of the DURATION-7 trial, more type 2 diabetes patients achieved a significant reduction in A1c with the GLP-1 agonist therapy after 28 weeks (165 of 204, 81%) versus those on combination titrated insulin glargine plus placebo (123 of 206, 60%).

Patients on titrated insulin glargine plus placebo were more likely to experience an increase in A1c levels after baseline (83 of 206, 40%), compared to those on the combination GLP-1 treatment (39 of 204, 19%).

Presenting the findings at the European Association for the Study of Diabetes meeting, coauthor Juan Frias, MD, of the National Research Institute in Los Angeles, also reported a greater prevalence of weight loss (at any degree) among patients on the exenatide therapy (62% versus 40%). In the same vein, those on the combination treatment were substantially less likely to report any weight gain during the trial (38% versus 60%).

Overall, nearly double the number of patients on the combination GLP-1RA treatment reported improvement for both A1c and body weight reduction compared to placebo plus insulin glargine (51% versus 23%), without an increase in hypoglycemic events.

It's just the latest study to find benefits of adding GLP-1 receptor agonists to basal insulin therapy, Frias explained. "There are clear improvements, or at least similar reductions in hemoglobin A1c compared to intensification of granular insulin, but with the benefits of a lower risk of hypoglycemia, generally weight loss, as opposed to weight gain," he stated, adding that ability to avoid daily injections is also better for the patient.

DURATION-7 included a total of 511 patients whose type 2 diabetes was not well controlled on basal insulin with or without stable metformin. At baseline, patients had an A1c of 7.5%-12.0%, on a minimum of 20 U/day of titration insulin glargine with or without combination metformin and sulfonylurea. Prior to randomization into the once-weekly exenatide with titrated insulin glargine with or without metformin (n=233) or placebo plus insulin glargine with or without metformin (n=231), use of all sulfonylureas was discontinued.

While an algorithm for insulin glargine titration was generally followed, Frias noted that the deviations were allowed as the discretion of the clinical investigator:

• Fasting glucose <72 mg/dL = -2 units IG dose change
• 72-99 mg/dL = 0 units
• 100-153 mg/dL= +2 units
• >153 mg/dL= +4 units

Adverse events were generally similar in the two groups, aside from the "expected" increase in gastrointestinal events -- including nausea, diarrhea, and vomiting -- and injection-site related adverse events in the exenatide group. No reports of severe hypoglycemia was reported in either group.

Session chairwoman Melanie J. Davies, MD, of the University of Leicester in England, inquired about possible indicators to predict success regarding patients who would better respond to this treatment. Frias responded that the idea was "worth looking at" in future studies, particularly to assess the differences between those who improved both A1c and body weight versus those who did not report any improved outcomes.

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