Early responders to liraglutide 3.0 mg as adjunct to diet and exercise from the SCALE Maintenance trial
Sean Wharton1, Søren Kruse Lilleøre2, Cecile H Jepsen2, Louis Aronne3
1. Wharton Medical Clinic, Weight and Diabetes Management, Hamilton, Canada.
2. Novo Nordisk, Søborg, Denmark.
3. Weill Cornell Medical University, New York, NY, USA.

Background: The SCALE Maintenance trial (NCT00781937) randomised adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with comorbidities who lost ≥5% of initial body weight during a 4–12-week low calorie diet (1200–1400 kcal/day) run-in period prior to randomisation to liraglutide 3.0 mg or placebo as adjunct to diet and exercise. Mean weight loss in the run-in period was ~6%. 
Aim: This is a post-hoc analysis of the SCALE Maintenance trial comparing outcomes in liraglutide 3.0 mg early responders (ERs) vs. early non-responders (ENRs) who completed 56 weeks of treatment (ERs vs. ENRs; ≥5% vs. <5% weight loss at week 16 after randomisation).
Method: Efficacy outcomes for liraglutide 3.0 mg ERs vs. ENRs are reported as observed means or proportions for individuals completing 56 weeks of treatment. The safety analysis set was used for adverse events.
Results: Mean characteristics at randomisation (n=212) for participants on liraglutide 3.0 mg were: 46 years of age, 84% female, BMI 36 kg/m². Of those who completed 56 weeks of treatment (n=159), 108 (68%) were ERs to liraglutide 3.0 mg and 51 (32%) ENRs. 91.7% of ERs maintained their run-in weight loss (or lost further weight) during 56 weeks of treatment vs. 47.1% of ENRs. The percentage of individuals who had regained all weight loss achieved during the run-in period by week 56 was 0.0% for ERs vs. 3.9% for ENRs. At week 56, greater mean and categorical weight loss and similar improvements in cardiometabolic risk factors were observed in ERs vs ENRs (Table). Adverse events (AEs) were reported in 92.7% of ERs vs. 91.0% of ENRs. For serious AEs, proportions were 4.9% vs. 0.0% and for gastrointestinal AEs 78.9% vs. 62.7% for ERs vs. ENRs respectively.

Table: Outcomes in ERs and ENRs who completed 56 weeks of treatment.
Change: change from randomization                                 Early responders to     Early non-responders to 
to week 56	                                                                            liraglutide 3.0 mg        liraglutide 3.0 mg
                                                                                                    n=108	                       n=51
Change in body weight (%)	                                             -9.9	                               0.0
Change in body weight (kg)	                                             -9.6	                               0.1
Proportion achieving ≥5% weight loss at week 56 (%)	     73.1	                             11.8
Proportion achieving >10% weight loss at week 56 (%)  47.2	                               0.0
Proportion achieving >15% weight loss at week 56 (%)  20.4	                               0.0
Change in mean waist circumference (cm)	                     -7.9	                               0.0
Change in FPG (mmol/L)	                                                     -0.6	                              -0.5
Change in HbA1c (%)	                                                             -0.2	                              -0.1
Change in SBP (mmHg)	                                                     -0.1	                              -0.5
Change in DBP (mmHg)	                                                      2.0	                               1.3

Discussion: Among those who completed 56 weeks of treatment, liraglutide 3.0 mg ERs achieved greater mean and categorical weight loss than liraglutide 3.0 mg ENRs, following ≥5% weight loss pre-randomization.