LAS VEGAS – The antidiabetic drug liraglutide promotes weight loss in overweight and obese individuals who do not have diabetes, according to results from a randomized trial reported on May 16 at the annual meeting of the American Association of Clinical Endocrinologists.
The 3,731 patients enrolled in the SCALE (Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities) trial were randomized 2:1 to treatment with once-daily subcutaneous 3.0 mg liraglutide or placebo, each along with caloric reduction and exercise. All patients were overweight or obese, with no known diabetes. About two-thirds had prediabetes.
At 56 weeks, patients given liraglutide had lost 8.0% of their body weight, compared with their counterparts given placebo, who had lost 2.6% (P less than .0001), reported lead author Dr. F. Xavier Pi-Sunyer, codirector of the New York Obesity Nutrition Research Center at St. Luke’s–Roosevelt Hospital Center, and professor of medicine at the Institute of Human Nutrition, Columbia University, in New York. The drug also had significant positive effects on various metabolic and lipid measures.
Rates of serious adverse events were similar with liraglutide and placebo, with the exception of pancreatitis and gallbladder disorders, which although still rare, were more than twice as common with the drug.
Liraglutide, in formulations of 1.2 mg and 1.8 mg for daily injections, was approved in 2010 for the treatment of type 2 diabetes and is marketed as Victoza. The 3.0-mg formulation used in SCALE is investigational.*
"Liraglutide 3.0 mg, as an adjunct to diet and exercise, was efficacious and generally well tolerated. It was associated with significant benefits in addition to weight loss, including improvement in hemoglobin A1c, fasting plasma glucose, blood pressure, and fasting lipids," Dr. Pi-Sunyer commented.
"The imbalance on pancreatitis and gallbladder disorders is undergoing further investigation," he added. "With regard to acute pancreatitis, no consistent mode or latency period was found. The majority of the events were mild according to the revised Atlanta criteria and were quickly reversible with stopping of the drug."
Session attendee Dr. Daniel Hurley, an endocrinologist at the Mayo Clinic in Rochester, Minn., asked, "In the patients with pancreatitis, any clinical idea whether this was gallstone induced or triglyceride induced?"
"Actually, the group that had the best result with regard to triglycerides did have a little more pancreatitis, so I don’t think it’s a triglyceride effect; in other words, the drug did drop triglycerides in these patients," Dr. Pi-Sunyer replied. "Only one patient developed both gallstones and pancreatitis; I don’t believe the two are probably related. We know that with weight loss, you get more gallstones and cholecystitis, and the drug group obviously had much better weight loss than the control group. I think that probably explains the gallbladder effect."
Liraglutide and other long-acting glucagonlike peptide–1 (GLP-1) receptor agonists are well known to decrease appetite and produce satiety, session comoderator Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, noted in an interview.
"So there’s a lot of interest now in using that not just for improving glucose metabolism in the diabetic, but as a weight loss agent. In the diabetes field, it’s really a two-fer – you basically improve glucose metabolism and you get the weight loss. But this is one of the first trials specifically just treating obesity without diabetes, and I’m sure they want to get FDA [Food and Drug Administration] approval for it" for this indication, he said. "It’s coming; we’re going to be using the GLP-1 receptor agonists for obesity," he predicted.
The 3.0-mg dose used in the trial is higher than the dose of 1.8 mg or so typically used in patients with diabetes, Dr. Horton noted. "There has been all the controversy about pancreatitis and so forth, and what was important here was showing that the higher dose didn’t increase the risk for any of these rare complications. But you have to be aware of them, and anybody who’s had pancreatitis, that’s a contraindication of course. But I think the drugs are safe even at the higher dose."
In the trial, patients given liraglutide (manufactured by Novo Nordisk) had significant improvements from baseline in waist circumference (–4.2 cm), body mass index (–2.0 kg/m2), fasting plasma glucose level (–6.9 mg/dL), hemoglobin A1c level (–0.2%), systolic and diastolic blood pressure (–2.8/–0.9 mm Hg), and fasting lipids.
The rate of serious adverse events was 6.2% with the drug and 5.0% with placebo. The respective rates of events leading to treatment discontinuation were 9.9% and 3.8%.