Liraglutide: A New Player in Type 1 Diabetes Treatment?

ORLANDO — The addition of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide (Victoza, Novo Nordisk) to insulin may offer multiple benefits for patients with type 1 diabetes, new research suggests.

Dr Paresh Dandona

Findings of a randomized, placebo-controlled, double-blinded, 1-year trial in 46 adults with type 1 diabetes were presented June 24 in a late-breaking poster here at the American Diabetes Association (ADA) 2018 Scientific Sessions by Paresh Dandona, MD, PhD, head of the division of endocrinology at the State University of New York at Buffalo.

During a press briefing, Dandona noted that since the discovery of insulin in 1921 "we've had improvements in the delivery of insulin and new insulin analogs, but still we are far from achieving the targets in the type 1 diabetes population. So clearly something additional is required."

In 2011, soon after liraglutide was approved in the United States for the treatment of type 2 diabetes, Dandona and colleagues published a small 12-week study demonstrating improved glycemic control, weight loss, and reduced systolic blood pressure with the agent in 14 patients with type 1 diabetes.

Now similar findings have been seen in this longer study of 46 patients funded by the National Institutes of Health.

Dandona said he believes the improvements are a class effect, as studies of other GLP-1 agonists have also shown benefit in type 1 diabetes.

"GLP-1 receptor agonists — liraglutide is a representative here — could be effective in type 1 diabetes in providing additional control, diminution of glycemic oscillations, and improved cardiovascular outcomes," he observed.

The mechanism for HbA_1c-lowering in type 1 diabetes with GLP-1 receptor agonists is likely caused by glucagon suppression, slowing of gastric emptying, appetite suppression, and weight loss, he noted.

Endocrinologist Fabiano M. Serfaty, MD, medical director of Serfaty Clinic, Rio de Janeiro, Brazil, and a consultant for the Portuguese site of Medscape agrees, calling liraglutide a possible new player in the treatment of type 1 diabetes.

"There are…hormones other than insulin that affect the blood sugar levels, like glucagon, GLP-1, gastric inhibitory polypeptide, amylin, cortisol, growth hormone, and epinephrine...Patients with type 1 diabetes have impaired beta-cell function, so insulin and amylin are reduced or absent and GLP-1 cannot act properly," Serfaty explained.

Elena Toschi, MD, of the Joslin Diabetes Center, Boston, Massachusetts, told Medscape Medical News that she has a few patients with type 1 diabetes who take liraglutide, but noted "the challenge is not all insurance plans cover it" because it's not approved for type 1 diabetes. She said it helps minimize postprandial glucose spikes and that gastrointestinal side effects, such as nausea, don't happen in all patients and tend to diminish with time when they do.

Other potential downsides include the fact that it's injected and patients must be screened for pancreatitis, certain types of cancer, and kidney stones. But as adjunctive therapies currently being studied in type 1 diabetes go, she believes liraglutide and metformin are generally safer than the sodium-glucose cotransport (SGLT) inhibitors, which carry the risk for diabetic ketoacidosis.

Indeed, Serfaty said, "We need to help patients with type 1 diabetes reduce their complications and improve their quality of life. Physicians and patients with type 1 diabetes don't have to be afraid of liraglutide, which is an effective and safe drug that improves the imbalance of the hormones that control blood glucose."

Multiple Benefits With Liraglutide in Type 1 Diabetes Up to 1 Year

Study participants were aged 30 to 75 years and had type 1 diabetes treated with multiple daily insulin injections or insulin pump. They had an average baseline HbA_1c of 9.92% and a body mass index of 28.9 kg/m². Patients were randomized to once-daily subcutaneous injections of liraglutide 1.8 mg (n = 26) or placebo (n = 20). Blinded continuous glucose monitoring (CGM) was performed for 4 weeks prior to treatment, at weeks 24 to 26, and weeks 48 to 52.

After the first 26 weeks, treatment was unblinded and the placebo group was switched to liraglutide so that all participants took liraglutide for the second 26 weeks.

At 52 weeks, placebo-adjusted HbA_1c had fallen by 0.57 percentage points in the group that started out taking liraglutide (P = .006 vs placebo), from 7.92% to 7.45% (P = .009).

The liraglutide group also experienced a 2.5-kg weight loss by 52 weeks (P = .041 vs placebo) and "an amazing" 9-mmHg drop in systolic blood pressure (P = .031), Dandona said.

Insulin dose and fasting and weekly glucose levels also fell, but there was no significant increase in reported hypoglycemia or time spent with glucose less than 70 mg/dL based on CGM data. C-peptide levels were nondetectable throughout the study.

Dandona is a consultant/advisor for and receives research support from AstraZeneca. Serfaty and Toschi have reported no relevant financial relationships.

American Diabetes Association 2018 Scientific Sessions. June 24, 2018; Orlando, Florida. Abstract 3-LB.

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