medwireNews: Combining exercise with the glucagon-like peptide (GLP)-1 receptor agonist liraglutide results in clinically relevant weight loss while maintaining bone mineral density (BMD) in people with obesity, Danish researchers report.
“A major concern with weight loss is concomitant bone loss,” explain Signe Sørensen Torekov and co-authors in JAMA Network Open. Therefore, “identifying treatments that induce clinically relevant weight loss while minimizing bone loss is essential in long-term obesity management,” they write.
Torekov and colleagues compared weight loss and changes in BMD in a secondary analysis of 195 clinical trial participants (mean age 43 years; 64% women) with obesity (mean BMI 37 kg/m2) who lost at least 5% of their body weight while following an 8-week, calorie-restricted diet (800 kcal/day). After the diet, the participants were randomly assigned to undertake a moderate-to-vigorous intensity exercise program (n=48), receive liraglutide 3 mg/day (n=49), a combination of the two interventions (n=49), or placebo (n=49) for 52 weeks.
The diet consisted of four low-calorie meal replacements per day while the exercise plan involved two group sessions per week, consisting of 30 minutes of indoor cycling and 15 minutes of circuit training, and encouragement to perform moderate-to-vigorous intensity exercise individually twice weekly.
At the end of the 8-week low-calorie diet, mean weight loss was 13.1 kg across the whole cohort. During the 52-week follow-up period, participants in the exercise and liraglutide groups maintained their weight loss, those in the combination group lost additional weight, and those given placebo regained weight. Specifically, at week 52, the average weight loss relative to the pre-diet baseline was 11.2 kg, 13.7 kg, 16.9 kg, and 7.0 kg, respectively.
The researchers report that although participants in the combination group lost more weight than those in the placebo group, there was no significant difference between these two groups in the change in total hip BMD from baseline to week 52. The mean reduction was a significant 0.019 g/cm2 in the combination group and a significant 0.012 g/cm2 in the placebo group. There was also no significant difference between the two arms in the change in lumbar spine BMD with respective, nonsignificant, reductions of 0.010 g/cm2 and 0.001 g/cm2 versus baseline.
“Thus, in the combination group, the preserved bone mass was observed despite a weight reduction of a magnitude that is clinically relevant in the context of novel incretin-based obesity therapies, such as semaglutide and tirzepatide,” Torekov et al remark.
Liraglutide alone also resulted in greater weight loss than placebo after 1 year, but unlike participants in the combination group, those in the liraglutide group experienced significantly greater bone density loss at the total hip and lumbar spine with significant BMD reductions of 0.026 g/cm2 and 0.020 g/cm2 versus baseline, respectively.
The corresponding BMD reductions in the exercise-only group were a significant 0.013 g/cm2 and a nonsignificant 0.003 g/cm2 versus baseline, which were significantly smaller than the decreases observed with liraglutide but no different to those seen with placebo.
Distal forearm BMD increased significantly from baseline to 1 year in the exercise and combination groups and did not change significantly in the other two groups. There were no significant differences among the four groups for this outcome.
Torekov et al conclude: “Collectively, our results show that the combination of exercise and GLP-1 [receptor agonist] was the most effective weight loss strategy while preserving bone health.”
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