Liraglutide 3.0 mg produced 6% weight loss in type 2 diabetes, SCALE Diabetes trial finds

The SCALE Diabetes trial found that adults with type 2 diabetes and excess weight lost an average of 6.0% of their body weight over 56 weeks while taking daily liraglutide 3.0 mg, compared with 2.0% among those taking a placebo ^[1].

The trial enrolled 846 people at 126 sites in 9 countries between June 2011 and January 2013 ^[1]. Participants were 18 or older, had a body mass index of 27.0 or higher, were taking up to three oral diabetes medicines (metformin, a thiazolidinedione or a sulfonylurea), had stable body weight, and had an A1c between 7.0% and 10.0% ^[1]. Everyone in the study also followed a diet with a 500-calorie daily deficit and did at least 150 minutes of physical activity a week ^[1].

People were assigned 2:1:1: 423 received liraglutide 3.0 mg once daily by injection, 211 received 1.8 mg, and 212 received placebo ^[1]. Starting weights were similar across the groups — 105.7 kg, 105.8 kg and 106.5 kg ^[1]. Average weight loss was 6.4 kg with 3.0 mg, 5.0 kg with 1.8 mg and 2.2 kg with placebo ^[1]. The estimated difference versus placebo was -4.00% (95% CI, -5.10% to -2.90%) for the 3.0 mg dose and -2.71% (95% CI, -4.00% to -1.42%) for 1.8 mg, both with P < .001 ^[1].

Just over half of the 3.0 mg group — 54.3% — lost at least 5% of body weight, compared with 40.4% at 1.8 mg and 21.4% on placebo ^[1]. Losing more than 10% occurred in 25.2%, 15.9% and 6.7% of those groups, respectively ^[1]. The trial's three co-primary endpoints at week 56 were relative weight change and the share of participants losing 5% or more or more than 10% ^[1].

Gastrointestinal disorders were reported more often with the 3.0 mg dose than with 1.8 mg or placebo, and no pancreatitis was reported ^[1]. The authors concluded that further studies are needed to evaluate longer-term efficacy and safety ^[1]. A separate correction notice about "Incorrect Data in Tables and eFigure" was published in JAMA in January 2016 ^[1].

The trial tested liraglutide in people who already had type 2 diabetes. The abstract does not report a direct comparison with weight loss in people who do not have diabetes, and results from a planned 12-week period after participants stopped the drug have not been reported ^[1]. The study did not test semaglutide (Ozempic, Wegovy, Rybelsus), tirzepatide (Mounjaro, Zepbound) or orforglipron, so its numbers do not describe those medicines ^[1].

Why it matters for patients

The trial rested on the idea that losing 5% to 10% of body weight can improve type 2 diabetes and related conditions, and that few safe, effective weight-management drugs were available when it began ^[1]. Its results describe what happened in one specific group: an average 6.0% loss on the 3.0 mg dose, with wide variation between individuals. Just under half of the people on 3.0 mg (45.7%) did not reach a 5% loss, and roughly three-quarters did not lose more than 10% ^[1].

Because every participant received diet and exercise support, the numbers reflect the drug plus that support, not the drug alone ^[1]. Side effects are part of the picture too: gastrointestinal problems were more common at the higher dose ^[1]. The results apply to liraglutide at the doses studied in this population, and not automatically to other GLP-1 or related medicines that were never part of the trial ^[1].