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Studies suggest growing potential for GLP-1 medications


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A growing body of evidence suggests that the use of glucagon-like peptide-1 (GLP-1) medications could become a common approach to improving glucose control in a variety of clinical situations. Studies presented on Saturday morning showed generally favorable results from novel and familiar GLP-1 receptor agonists in type 2 diabetes, type 1 diabetes, and cardiac surgery.

Richard E. Pratley, MD
Richard E. Pratley, MD

A novel oral formulation of semaglutide, which has been submitted to the U.S. Food and Drug Administration for approval, is noninferior to liraglutide in reducing A1C and provided better weight loss, according to Richard E. Pratley, MD, of the Adventhealth Translational Research Institute for Diabetes and Metabolism, who presented the results of the 52-week PIONEER 4 study, which was published simultaneously in The Lancet.

“Given that many with type 2 diabetes are reluctant to inject themselves daily, an oral formulation may get more patients on treatment faster,” Dr. Pratley said.

Dr. Pratley also presented a subanalysis of the BALANCE 205 study of efpeglenatide, a long-acting GLP-1 receptor agonist in development for type 2 diabetes. The 20-week study compared four doses of efpeglenatide (4 mg weekly, 6 mg weekly, 6 mg every two weeks, and 8 mg every two weeks) to placebo. All of the doses showed significant improvements in A1C, body mass index, and weight circumference in a subgroup of patients with prediabetes.

Thomas F. Dejgaard MD, PhD
Thomas F. Dejgaard, MD, PhD

Diabetes is not the only cause of hyperglycemia. Most cardiac surgery patients develop perioperative hyperglycemia that’s usually treated with intravenous insulin. The multicenter Liraglutide for Perioperative Management of Hyperglycaemia in Cardiac Surgery Patients (GLOBE) trial found that 0.6 mg liraglutide given the day before surgery and 1.2 mg the day of surgery reduces the need for insulin in the operating room compared to placebo.

“Liraglutide reduces the need for insulin during and after cardiac surgery,” said Abraham H. Hulst, MD, of Amsterdam Universitair Medische Centra in the Netherlands. ”Perioperative liraglutide improves glycemic control during both the intraoperative and postoperative periods.”

GLP-1 receptor agonists have shown modest effects on glycemic control in type 1 diabetes. Patients with elevated C-peptide levels generally have a greater benefit, noted Thomas F. Dejgaard, MD, PhD, of the Steno Diabetes Center in Copenhagen, Denmark. Rodent studies show that GLP-1 agonists increase beta-cell mass by inducing neogenesis and preventing beta-cell apoptosis.

Tricia M. Tan BSc, MB ChB, FRCP, PhD, FRCPath
Tricia M. Tan, BSc, MBChB, FRCP, PhD, FRCPath

“Adding on 1.8 mg liraglutide to insulin preserved insulin secretion compared to placebo, reduced insulin dose, and reduced self-monitored hypoglycemia,” Dr. Dejgaard reported. “We did not see any changes in body weight, A1C, or glucose profile.”

Roux-en-Y gastric bypass (RYGB) can produce sustained weight loss and diabetes improvements, at least in part by increasing gut secretion of GLP-1, oxyntomodulin (OXM), and peptide YY (PYY). Early work at Imperial College London in Great Britain replicated glycemic improvements of RYGB by infusing a combination of GLP-1, OXM, and PYY. Patients in the study group reduced their caloric intake by 32 percent and lost 4.4 kg over the 28-day study, reported Tricia M. Tan, BSc, MBChB, FRCP, PhD, FRCPath, a Consultant in Diabetes, Endocrinology, and Metabolic Medicine at the college. A comparator group of RYGB patients lost 10.3 kg.

“Our study group had glucose improvements comparable with RYGB and had better glucose tolerance than RYGB even though RYGB had twice the weight loss,” Dr. Tan said.