LAS VEGAS — The glucose-lowering drug liraglutide (Victoza, Novo Nordisk) promotes weight loss in overweight and obese people who don't have diabetes, according to the results of the multinational SCALE — Obesity and Prediabetes trial, presented here at the American Association of Clinical Endocrinologists (AACE) 23rd Annual Scientific and Clinical Congress.

The injectable glucagonlike peptide-1 (GLP-1) agonist performed significantly better than placebo, producing weight loss comparable to that of already-approved weight-loss drugs in other trials, said Xavier Pi-Sunyer, MD, professor of medicine at Columbia University College of Physicians and Surgeons in New York City and codirector of the New York Obesity Nutrition Research Center.

"Patients lost 8% of their body weight from baseline," he told Medscape Medical News. "That's as good as any drug out there. It's better than anything except [phentermine-topiramate], and it's about as good as [phentermine-topiramate]. I think it stacks up pretty well."

On September 11, 2014, a US Food and Drug Administration advisory panel is scheduled to review liraglutide 3.0 mg — a higher dose than the approved 1.8-mg dose used for diabetes — for the new obesity indication.

There was significantly more nausea and vomiting with liraglutide compared with placebo in SCALE, but it resolved with time.

Also, a slightly elevated risk for pancreatitis and gallbladder disorders was seen among patients randomized to liraglutide compared with placebo. "The net effect was under 1% but was slightly more for the drug vs placebo group. It is being investigated and people are being followed," said Dr. Pi-Sunyer.

Low rates of these events preclude any conclusion about causation, Farhad Zangeneh, MD, director of the Endocrine, Diabetes, and Osteoporosis Clinic, Sterling, Virginia, told Medscape Medical News. "Obesity and diabetes [themselves] cause pancreatitis and gallbladder issues. There's a lot of background noise," he said. Dr. Zangeneh was not involved in the study.

Weight Loss

The study enrolled 3731 individuals with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with 1 or more comorbidities. Participants were randomized 2:1 to receive once-daily subcutaneous liraglutide 3.0 mg or placebo, along with diet and exercise.

Of the 2590 patients who completed the 56-week study, 78.5% were female with a mean age of 45 years, mean body weight of 106 kg, and mean BMI of 38 kg/m2. Nearly two-thirds had prediabetes. More patients on liraglutide completed the study than those on placebo (72% vs 64%).

At week 56, the liraglutide group had lost 8.0% of their body weight (8.4 kg), compared with 2.6% (2.8 kg) in the placebo group (P < .0001). The proportion of patients who lost 5% or more of their body weight was 64% with liraglutide 3.0 mg vs 27% with placebo (P < .0001); 33% and 10%, respectively, lost more than 10% of their body weight.

Weight loss was independent of prediabetes status or baseline BMI, Dr. Pi-Sunyer reported.

The liraglutide group experienced blood-pressure drops of 2.82 mm Hg (systolic) and 0.89 mm Hg (diastolic). Lipid profiles improved as well, with increases in HDL cholesterol and reductions in LDL and VLDL cholesterol and triglycerides (overall significance P < 0.02).

Gastrointestinal Side Effects

Mild to moderate nausea and vomiting were the most frequently reported side effects. Withdrawal rates due to adverse events — primarily gastrointestinal — were 9.9% for liraglutide vs 3.8% for placebo.

Most of the nausea and vomiting occurred early on, within the first 4 weeks, Dr. Pi-Sunyer told Medscape Medical News. "That's why you do a dose titration, starting with 0.6 mg and work your way up by 0.6-mg increments. Patients get better after 4 to 5 weeks. By 56 weeks, you have very few people who have a problem with [these side effects]."

Rates of gallbladder disorders and pancreatitis were 2.7 and 0.3 events per 100 patient-years for liraglutide, respectively, and 1.1 and 0.1 events per 100 patient-years for placebo, respectively. Both pancreatitis and gallbladder-related problems were reported in 1 patient in the liraglutide group and 1 patient in the placebo group.

The new framework for treating obesity as a chronic disease, previously reported on by Medscape Medical News , requires as much focus on obesity as on diabetes, said Dr. Zangeneh. Lifestyle modifications and medical therapy are needed for both conditions, he said. "Everything in medicine [has a] risk/benefit ratio. To leave people obese is not without risk."

Dr. Pi-Sunyer is on the advisory boards for Novo Nordisk, Vivus, Eisai, Zafgen and Lilly. Dr. Zangeneh is a consultant and/or speaker for Novo Nordisk, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Eisai, Vivus, AbbVie, Janssen, and Bristol-Myers Squibb.

American Association of Clinical Endocrinologists 23rd Annual Scientific and Clinical Congress. Presented May 16, 2014.


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