Liraglutide 3.0 mg produced more weight loss than placebo in 56-week trial

Adults without type 2 diabetes who injected liraglutide 3.0 mg once daily lost a mean of 8.4 kg over 56 weeks, compared with 2.8 kg for those who received a placebo, according to results published July 2, 2015, in the New England Journal of Medicine ^[1][2]. Liraglutide is a glucagon-like peptide-1 (GLP-1) analog ^[1].

How the trial was set up

The double-blind trial enrolled 3,731 patients at 191 sites in 27 countries and ran from June 1, 2011, through March 18, 2013 ^[1]. Patients were randomly assigned in a 2:1 ratio to liraglutide 3.0 mg (2,487 people) or placebo (1,244 people). Both groups received counseling on lifestyle modification ^[1][2].

To join, patients had to have a body-mass index of at least 30, or at least 27 if they had treated or untreated dyslipidemia or hypertension. People with type 1 or type 2 diabetes were excluded ^[1].

At the start, the mean age was 45.1 years, mean weight was 106.2 kg and mean BMI was 38.3. Of the participants, 78.5% were women and 61.2% had prediabetes ^[1][2].

Liraglutide was injected under the skin once a day, starting at 0.6 mg and increasing by 0.6 mg each week to reach 3.0 mg ^[1].

What the numbers showed

Three goals were set in advance: change in body weight, the share of patients losing at least 5% of starting weight, and the share losing more than 10% ^[1].

The difference in average weight loss between the two groups was −5.6 kg (95% confidence interval, −6.0 to −5.1; P<0.001) ^[1][2].

In the liraglutide group, 63.2% lost at least 5% of body weight, compared with 27.1% on placebo. And 33.1% lost more than 10%, compared with 10.6% on placebo. Both differences were statistically significant (P<0.001) ^[1][2].

The most frequently reported side effects with liraglutide were mild or moderate nausea and diarrhea. Serious adverse events occurred in 6.2% of the liraglutide group and 5.0% of the placebo group ^[1][2].

By week 56, 71.9% of the liraglutide group and 64.4% of the placebo group had completed treatment ^[1].

The trial was funded by Novo Nordisk, which also planned and performed the statistical analyses, provided editorial and writing assistance, and supplied the trial drugs ^[1]. Its registration number is NCT01272219 ^[1][2].

Why it matters for patients

Weight loss of 5% to 10% has been shown to reduce complications related to obesity and improve quality of life, while weight loss is difficult to maintain with lifestyle intervention alone, the paper notes ^[1].

In this trial, about one in three people on liraglutide lost more than 10% of their body weight, a result reached by about one in ten on placebo ^[1]. The average loss, however, was 8.4 kg, and results varied widely from person to person — the standard deviation was 7.3 kg ^[1]. More than a quarter of the liraglutide group did not complete the 56 weeks ^[1].

Because everyone in the trial also received diet and exercise counseling, the results reflect the drug plus counseling, not the drug alone ^[1].

The study enrolled only people without diabetes, so the numbers do not describe what happens in patients with type 2 diabetes ^[1]. Liraglutide was already approved for type 2 diabetes at doses up to 1.8 mg once daily; the 3.0 mg dose used here is higher than that ^[1].

What happens next

A two-year extension of the trial, involving patients with prediabetes, was designed to test whether liraglutide delays the onset of type 2 diabetes and had recently been completed when these results were published ^[1]. The extension's results are not reported in this article ^[1].

After week 56, patients who did not have prediabetes were assigned at random, 1:1, either to keep taking liraglutide or to switch to placebo for 12 weeks, to assess whether the effect was maintained after the drug was stopped and whether there were safety issues related to stopping it ^[1]. Those findings are also not reported in this article ^[1]. Whether the 3.0 mg dose would be reviewed or approved for weight management in the United States has not been reported ^[1].