Saxenda becomes first GLP-1 drug approved for weight management

Saxenda (liraglutide 3.0 mg), a once-daily injection, became the first GLP-1 receptor agonist approved in the United States for chronic weight management, according to federal drug listing records that show a marketing start date of Dec. 31, 2014 ^[1]. The trial behind the approval found that adults without type 2 diabetes lost a mean of 8.4 kg over 56 weeks on the drug, compared with 2.8 kg on placebo ^[2].

Federal listing data describe Saxenda as a prescription product containing liraglutide at a strength of 6 mg/mL, given by subcutaneous injection, supplied in 3 mL plastic syringes under application number NDA 206321 ^[1]. Liraglutide is listed in the same record as a GLP-1 receptor agonist ^[1].

The supporting study, called SCALE Obesity and Prediabetes, was a 56-week double-blind randomized trial that enrolled 3,731 adults who did not have type 2 diabetes ^[2]. To join, participants had to have a body-mass index of at least 30, or a BMI of at least 27 along with treated or untreated dyslipidemia or hypertension ^[2]. They were assigned in a 2:1 ratio to liraglutide 3.0 mg (2,487 people) or placebo (1,244 people), and both groups received counseling on diet and exercise ^[2]. At the start, the mean age was 45.1 years, mean weight was 106.2 kg and mean BMI was 38.3; 78.5% of participants were women and 61.2% had prediabetes ^[2].

At week 56, the liraglutide group had lost a mean of 8.4 kg and the placebo group a mean of 2.8 kg, a difference of 5.6 kg (95% confidence interval, -6.0 to -5.1; P<0.001), calculated with last-observation-carried-forward imputation ^[2]. Individual results varied widely: the standard deviation was 7.3 kg in the liraglutide group and 6.5 kg in the placebo group ^[2]. In all, 63.2% of people on liraglutide lost at least 5% of their starting body weight versus 27.1% on placebo, and 33.1% versus 10.6% lost more than 10% ^[2].

The most frequently reported side effects with liraglutide were mild or moderate nausea and diarrhea ^[2]. Serious events were reported in 6.2% of the liraglutide group and 5.0% of the placebo group ^[2]. The trial was funded by Novo Nordisk and registered as NCT01272219 ^[2].

Some limits are built into the results. The study excluded people with type 2 diabetes, and it followed participants for 56 weeks, so effects beyond that period were not captured ^[2]. The trial tested the drug alongside diet and exercise counseling, not on its own ^[2]. Whether weight loss is maintained after the drug is stopped has not been reported in these results ^[2].

Why it matters for patients

This was the first time a GLP-1 receptor agonist was cleared for weight management, which opened the path for later obesity drugs in the same class ^[1]. For patients, the practical details in the record are dosing and delivery: a daily subcutaneous injection of a 6 mg/mL solution ^[1].

The average result in the trial was about 8.4 kg, but the spread around that average was wide ^[2]. A mean figure does not predict what any one person will lose, and roughly a third of participants on the drug lost more than 10% of their body weight while about two-thirds did not reach that mark ^[2].

Gastrointestinal side effects were the most common complaints, and they were mostly mild or moderate ^[2]. Serious events were slightly more frequent on the drug than on placebo in this trial, 6.2% versus 5.0% ^[2].

Access conditions in the trial were tied to BMI: at least 30, or at least 27 with dyslipidemia or hypertension ^[2]. People with type 2 diabetes were not part of this study, so its numbers do not describe that group ^[2].

Questions that patients often ask about weight drugs — how long to stay on treatment, what happens after stopping, and what it costs — are not answered by the approval record or the published trial results ^[1][2].