Combined exercise + liraglutide maintains healthy weight loss in obese people

Combining exercise and liraglutide treatment is more effective in improving and maintaining healthy weight loss than either strategy alone in people with obesity, reveals a head-to-head study.

“Weight regain after weight loss is a major problem in the treatment of persons with obesity,” the researchers pointed out. “Many patients have an initial large weight loss [after treatment], but weight regain often occurs unless a structured weight-maintenance programme is followed.”

This head-to-head, placebo-controlled trial compared four strategies: moderate-to-vigorous–intensity exercise, subcutaneous liraglutide 3.0 mg per day, combined exercise and liraglutide, or control (ie, usual activity plus placebo injection). Participants were 195 adults (mean age 43 years, 64 percent female) who were obese (BMI 32–43, mean body weigh 96.7 kg) but did not have diabetes. They were randomized to either one of the four strategies for 1 year, following an 8-week low-calorie diet. [N Engl J Med 2021;384:1719-1730]

After 1 year, all three active treatment strategies led to weight loss that was significantly greater than the control strategy — with the greatest weight loss seen in the combined exercise plus liraglutide group (difference, −4.1 kg; p=0.03 with exercise, −6.8 kg; p<0.001 with liraglutide, and −9.5 kg; p<0.001 with combined strategy).

The combination strategy also induced significant weight reduction by 5.4 kg more compared with exercise (p=0.004), but not when compared with liraglutide (−2.7 kg; p=0.13).

“The combination of exercise and liraglutide therapy … resulted in a total weight loss of 16 percent. This is more than the total weight losses of approximately 10 percent that were obtained with 1-year diet-management programmes after an initial low-calorie diet,” the researchers highlighted.

“[On the other hand,] participants in the placebo group regained, on average, 6.1 kg, which was equivalent to 45 percent of the weight that they had initially lost [after the 8-week low-calorie diet],” they added.

While all three active treatment strategies also reduced the proportion of body fat compared with control, the benefit was greatest in the combination strategy group. Body-fat composition reduced by 3.9 percentage points in the combination group, which was approximately double the decrease seen in either the exercise group (−1.7 percentage points; p=0.02) or the liraglutide group (−1.9 percentage points; p=0.009).

“The combination of exercise and liraglutide treatment was associated with loss of fat mass and reduction in waist circumference that were approximately twice those observed with the single treatments, and it preserved lean mass,” the researchers reported.

Furthermore, the combination strategy was associated with additional benefits, including improvements in cardiorespiratory fitness, HbA1c level, insulin sensitivity, physical functioning, and emotional well-being.

In contrast, the control group saw reversal of all associated metabolic health-related gains. 

While increase in resting heart rate was observed in participants treated with liraglutide alone, this increase was not seen when liraglutide therapy was combined with exercise — supporting the health-promoting potential of the combination strategy.

Cholelithiasis also occurred more frequently with liraglutide alone than the combination strategy.

“This result shows the critical importance of implementing structured treatment after weight loss, as compared with a strategy of just 12 individualized consultations regarding weight and diet, as provided in the current trial … for sustained weight loss,” the researchers concluded.

The stable adherence to the exercise programme supports the feasibility of such strategy, they noted. Nonetheless, they also acknowledged that the findings might not be generalizable to older people aged >65 years, severely obese people with BMI >43, patients with coexisting conditions (such as type 2 diabetes), and people with low adherence or limited ability to carry out moderate-to-vigorous–intensity exercise.