Exercise Plus Liraglutide Good for Weight Loss Maintenance

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide were roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine.

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.

Hope for Healthy Weight Loss Maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”

Obesity and Weight-Loss Challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.

Weight Loss With Exercise and Medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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