• Weight regain after weight loss is a major problem in the treatment of persons with obesity.
  • The occurrence of obesity is greater than ever, with unfavorable effects on health and increases the risk of death. Many patients have preliminary weight loss, but weight regain frequently occurs unless a structured weight-maintenance program is followed. Rapid weight regain may be due to a decline in total energy expenditure, beyond that predicted from the loss of lean and fat mass, and to increased appetite.
  • A lessen in body weight of 3 to 5% has been related with decreased  obesity-related risk factors, while a larger weight loss of above 5 to 15% of the preliminary body weight is suggested for patients with coexisting conditions, morbid obesity, or both.
  • Structured aerobic exercise programs increase energy expenditure and cardiorespiratory fitness although reducing fat mass and preserving or increasing lean mass. Diet management programs, including the use of low-calorie meal alternate products, can sustain low-calorie diet–induced weight loss with a small weight regain. In addition, lifestyle interventions that promote increased physical activity concurrent with calorie restriction have been shown to sustain moderate weight loss.
  • Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used in the treatment of obesity because it induces weight loss and maintains low-calorie diet–induced weight loss for at least 1 year, mainly by means of appetite inhibition.
  • Whether exercise, medication, or a combination strategy constitutes the extra effective approach for maintaining healthy weight loss . The study investigated the efficacy of 1-year treatment with a moderateto-vigorous–intensity exercise program, liraglutide at a dose of 3.0 mg per day, or the combination of exercise plus liraglutide, as compared with placebo, for healthy weight loss maintenance after weight loss induced by a low-calorie diet.
  • The exercise program was designed to meet the World Health Organization (WHO) recommendations on physical activity for health of a minimum of 150 minutes per week of moderate-intensity aerobic physical activity, or 75 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination of both. After an initial 6-week rampup phase, participants were encouraged to attend supervised group exercise sessions (which involved 30 minutes of vigorous-intensity, interval-based indoor cycling and 15 minutes of circuit training) two times per week and to perform moderate-tovigorous–intensity exercise individually (which mostly involved outdoor or indoor cycling, running, or brisk walking) two times per week.
  • Liraglutide (at a concentration of 6 mg per milliliter) or volume-matched placebo was injected subcutaneously, starting at a dose of 0.6 mg per day, with supervised weekly increments of 0.6 mg per day; the dose was intended to eventually reach 3.0 mg per day.
  • During the 8-week low-calorie diet, the participants’ body weight decreased by a mean of 13.1 kg, which was equivalent to a mean reduction in body weight of 12%. This decrease was accompanied by decreases in the body-fat percentage, waist circumference, waist-to-hip ratio, glycated hemoglobin level, blood pressure, lipid levels, resting heart rate, and HOMA-IR. The Matsuda index, cardiorespiratory fitness, general health perception, physical functioning, and emotional well-being increased.
  • After the low-calorie diet, the participants’ body weight decreased further by a mean of −3.4 kg in the combination group but increased by a mean of 6.1 kg in the placebo group, resulting in a treatment difference of −9.5 kg. The initial weight loss was maintained in the exercise group, with a treatment effect as compared with placebo of −4.1 kg. Liraglutide treatment also resulted in maintenance of the initial weight loss, with a treatment effect as compared with placebo of −6.8 kg. In the combination group, the treatment effect as compared with exercise was −5.4 kg and the treatment effect as compared with liraglutide was −2.7 kg.
  • All active treatments (i.e., those involving exercise, liraglutide treatment, or both) were associated with decreases in fat mass and waist circumference, as compared with increases in the placebo group, and the decreases were twice as large in the combination group as in the other groups. Exercise was associated with increased lean mass. Exercise and the combination strategy were associated with increased cardiorespiratory fitness, which was not observed with placebo or liraglutide . Liraglutide treatment and the combination strategy were associated with reductions in the glycated hemoglobin level, as compared with an increase in the placebo group. Only the combination strategy was associated with reductions in the HOMA-IR and the waist-to-hip ratio and with increases in the Matsuda index and in physical functioning, as compared with placebo. All active treatments were associated with maintained reductions in the systolic and diastolic blood pressures, which were not observed with placebo. Exercise and the combination strategy were associated with maintenance of the initial improvements in general health perception and emotional wellbeing, which were not observed with placebo or liraglutide.
  • Adverse events that occurred in at least 10% of all participants, urinary tract infections, palpitations, and all serious adverse events are reported. Few participants which are receiving liraglutide and placebo discontinued taking liraglutide or placebo because of adverse events. Gastrointestinal adverse events, decreased appetite, and dizziness were more frequently reported in the groups that received liraglutide (i.e., in the liraglutide group and combination group) than in the other two groups. Cholelithiasis as a serious adverse event and palpitations were reported more frequently in the liraglutide group than in the combination group. After 1 year, liraglutide treatment alone was associated with an increased resting heart rate; this finding was not observed with the combination strategy. The incidence of other adverse events was similar among the trial groups.
  • In this randomized, head-to-head, placebo-controlled trial, Investigated that exercise, liraglutide, and both treatments combined for healthy weight loss maintenance. All active-treatment groups decreased body weight and body-fat percentage after 1 year, as compared with the increases observed in the placebo group. The combined strategy reduced the body weight and body-fat percentage approximately twice as much as the single-treatment strategies did and was associated with additional health benefits, such as improvements in the glycated hemoglobin level, insulin sensitivity, cardiorespiratory fitness, physical functioning, and emotional well-being.

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