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GLP-1 Drug Boosts T1D Control

— A1c, glucose, weight, blood pressure all improved in randomized trial

Ƶ MedicalToday

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ORLANDO -- Adding the GLP-1 analog liraglutide (Victoza) to conventional insulin treatment for type 1 diabetes improved glycemic control as well as other cardiometabolic parameters, a randomized trial showed.

Hemoglobin A1c came out 0.57% lower with liraglutide than with placebo, with the liraglutide group dropping from 7.9% to 7.45% at 52 weeks (P=0.006 vs placebo to week 26, P=0.009 vs baseline), reported Paresh Dandona, MD, PhD, of the State University of New York at Buffalo, at the American Diabetes Association annual meeting.

The A1c impact was surprisingly larger than the roughly 0.3% effect seen in a prior pilot study, he noted at an ADA press conference.

The double-blind trial in 46 adults, randomized to daily 1.8-mg liraglutide injections or placebo atop an insulin regimen well-titrated during run-in, also showed significant reductions of 2.5 kg (5.5 lb) placebo-adjusted weight loss and 9 mm Hg in systolic blood pressure with the additional medication.

A1c, blood pressure, and weight impacts of liraglutide were similar at the end of the trial between the placebo group unblinded and crossed over to the drug at 26 weeks and those on liraglutide the whole 52 weeks. Hypoglycemia was not increased at any point with liraglutide.

"If you have a glycemic improvement, if you have weight loss, you have falling blood pressure, you are having a remarkable reduction overall in cardiovascular risk," Dandona suggested at the press conference.

These effects were despite no detectable C-peptide at baseline or on treatment, suggesting the mechanism wasn't activating beta cell reserves to produce insulin that would reach the periphery, Dandona noted.

While GLP-1 drugs are used in type 2 diabetes mainly to potentiate glucose-stimulated insulin secretion, they also inhibit glucagon secretion, delay gastric emptying, and reduce body weight. "I believe it's a class effect," Dandona noted.

ADA press conference moderator Bernard Zinman, MD, of the Mount Sinai Hospital in Toronto, agreed.

"There is good reason to believe that insulin and a GLP-1 receptor agonist are a very good couple. They work very well together in type 2 diabetes," he told Ƶ. "I think that we will see more GLP-1 receptor agonists being used in type 1 diabetes."

Steven Kahn, MB ChB, of the University of Washington in Seattle, commented that this is part of an effort to reduce the need for insulin and hyperglycemia. SGLT2 medications are also moving into type 1 diabetes, though DPP4s are unlikely to be used.

As to whether the additional half a percentage point of A1c reduction would be worthwhile for the cost of a GLP-1 drug, "it all depends on what the patient can afford and is willing to do," Kahn, who was not involved in the study, told Ƶ. Although if these drugs could be used to reduce insulin needs and thus risk of severe hypoglycemia episodes requiring medical attention, there would be potential for cost savings, he noted.

Disclosures

The study was supported by the NIH.

Dandona disclosed relevant relationships with AstraZeneca.

Kahn disclosed relevant relationships with Boehringer-Ingelheim, Janssen, and Novo Nordisk.

Primary Source

American Diabetes Association

Dandona P, et al "Liraglutide as an Additional Treatment to Insulin in Patients with Type 1 Diabetes Mellitus–A 52-Week Randomized Double-Blinded Placebo-Controlled Clinical Trial" ADA 2018; Abstract 3-LB.