A year of regular exercise plus daily subcutaneous injections of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was superior to placebo or liraglutide or exercise alone in maintaining weight loss, in a new study.
The S-LITE trial randomized close to 200 healthy patients with obesity but no diabetes who had lost at least 5% of their initial weight on an 8-week very low-calorie diet to one of these four treatment regimens for weight-loss maintenance.
With the combined treatment, the patients not only kept the most weight off, they also lost the most body fat while preserving muscle mass.
“Therefore, we recommend this combined use of exercise and liraglutide after weight loss,” Julie R. Lundgren, MD, and a PhD student, concluded in her oral presentation of the trial results during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
The study shows “how important it is to initiate a strategy for weight [loss] maintenance,” Lundgren and senior author Signe S. Torekov, PhD, both from the University of Copenhagen, Denmark, told Medscape Medical News in an email.
“It is not enough to go on a diet and lose weight,” they stressed. Patients need “some kind of active treatment after the weight loss in order to maintain [this lower] weight and health benefits” that go along with it.
This combined treatment would most likely also help patients with type 2 diabetes maintain weight loss, they speculated. Although, they added, “depending on how long you have had type 2 diabetes, it may be more difficult to reverse adverse effects of type 2 diabetes.”
Therefore, it is better to lose weight before developing diabetes (for which obesity is a risk factor).
What Is the Best Way to Prevent Weight Regain?
S-LITE was a randomized placebo-controlled trial designed to investigate 1-year weight-loss maintenance and change in body fat and muscle mass using four strategies in healthy patients with obesity.
The trial enrolled 215 participants who were 18-65 years old with a body mass index (BMI) of 32-43 kg/m2 and no diabetes or previous bariatric surgery, who did less than 2 hours of vigorous exercise a week.
On average, the participants were 42 years old, weighed 107.6 kg (237 lb), and had a BMI of 36.5 kg/m2; 64% were women.
After an 8-week very low-calorie diet (800 kcal/day), 195 patients (91%) had lost the required ≥ 5% of body weight and were able to enter the maintenance phase.
They were randomized to 1 year of treatment with liraglutide 3.0 mg/day; exercise 150 minutes/week (plus placebo); exercise 150 minutes/week plus liraglutide 3.0 mg/day (combination); or placebo.
Participants injected themselves with either placebo or liraglutide daily (depending on what group they were in).
The exercise intervention consisted of two supervised sessions per week and two individual sessions per week, to reach 150 minutes/week of activity.
The supervised exercise sessions, which took place in the department of physiology, Hvidovre Hospital, consisted of 30 minutes of high-intensity interval-based cycling and 15 minutes of circuit training, guided by exercise trainers affiliated with the study.
The drop-out rate was low.
At 1 year, 41 of 49 randomized patients in the liraglutide group, 40 of 48 patients in the exercise group, 45 of 49 patients in the combination group, and 40 of 49 patients in the placebo group completed the study.
Greatest Success With Combined Strategy
At the start of the weight-loss maintenance phase, participants had lost an average of 13.1 kg.
At 1 year, patients in the liraglutide only group had lost an additional 0.7 kg; patients in the exercise group had regained 2.0 kg; and participants in the placebo group had regained about half of what they had lost (6.1 kg).
However, participants in the combined exercise and liraglutide group had lost an additional 3.4 kg.
Moreover, participants in the liraglutide and exercise group lost fat while preserving lean muscle mass.
At the start of the weight-loss maintenance phase, participants had lost an average of 2.3% of their body fat.
After 1 year, participants in the combined liraglutide and exercise group had lost an additional 3.5% of their body fat — which was greater than the loss of body fat in the exercise group (1.8%) and liraglutide group (1.6%), or the gain of body fat in the placebo group (0.4%).
“The compliance to both study medication and the exercise program was very high in our study,” Torekov and Lundgren said, “so we consider the combined treatment strategy as feasible with the correct guidance and supervision.”
However, they stressed that guided exercise is especially important when initiating a program for untrained individuals, and studies have shown that it may be more difficult to adhere to long-term unsupervised exercise programs.
And the cost of liraglutide may be a potential drawback for some individuals, they acknowledged.
Likewise, exercising at a gym may be costly, “but it is also possible to exercise outside the gym on your own for free, for example by cycling, brisk walking, or running.”
Moreover, “later treatment of the comorbidities associated with obesity (type 2 diabetes, cardiovascular disease, etc) is also costly,” they point out.
“In general, the participants liked the treatment programs as is also reflected in the low dropout rate and high adherence to the programs,” the researchers concluded.
Torekov has reported receiving research support from Novo Nordisk. Lundgren has reported no relevant financial relationships. Disclosures for the other authors are listed in the abstract.
ADA 2020 Scientific Sessions. Presented June 13, 2020. Abstract 139-OR.