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GLP-1 and bone loss

GLP-1 treatment prevents bone loss during weight loss

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The results may have a significant bearing on future obesity treatment

Using the intestinal hormone glucagon-like peptide 1 (GLP-1) in obesity treatment prevents the loss of bone mass otherwise frequently associated with major weight loss, according to a study from the University of Copenhagen, Hvidovre and Glostrup Hospital, Denmark. According to the researchers behind the study, the results may have a significant bearing on future obesity treatment.

It is known that rapid weight loss can lead to a loss of bone mass and an increased risk of bone fractures. The Danish research shows that treating obesity with the GLP-1 hormone helps prevent loss of bone mass in addition to having a number of positive effects on the formation of new bone and on blood sugar levels.

"GLP-1 analogues like liraglutide are today widely used in the treatment of type 2 diabetes and have been shown not to increase the risk of bone fractures, unlike other diabetes drugs,” said physician and PhD student, Eva Winning Jepsen from the Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen. “Liraglutide has just been approved for obesity treatment because of its appetite-inhibiting effects, but its effect on the bones of overweight patients who are not suffering from type 2 diabetes has so far been unknown."

The study looked at 37 women who achieved a large weight loss of 12kg by eating a low-calorie diet. The women were divided into two groups: one which was given the GLP-1 analogue liraglutide, and a control group. Over a one-year period, the women were given frequent dietary advice to help them maintain their weight loss; and if they gained weight, they could replace up to two meals with a low-calorie powder.

The researchers recorded the total, pelvic and arm-leg bone mineral content (BMC) and bone markers (CTX-1 and P1NP) before, after weight loss and after 52 weeks weight maintenance. Primary end points were the change in BMC and bone markers after 52 weeks weight maintenance with or without GLP-1 RA treatment.

They report that total, pelvic and arm-leg BMC decreased during weight maintenance in the control group (p<0.0001), but not significantly in the liraglutide group. Thus, total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group (estimated difference 27g (95% CI 5–48), p=0.01), although the 12% weight loss was maintained in both groups. In the liraglutide group, the bone formation marker P1NP increased by 16% (7±3μg/L) vs a 2% (-1±4μg/L) decrease in the control group (p<0.05). The bone resorption marker CTX-1 did not change during the weight loss maintenance phase.

Therefore, the study showed that the liraglutide group had not lost any bone mass and had increased blood levels of bone formation markers as opposed to the control group which had lost bone mass.

"Menopausal women have an increased risk of osteoporosis and bone fractures. If they try to lose weight and thus lose even more bone mass, they are at an even higher risk,” said lead researcher, Associate Professor Signe Soerensen Torekov from the Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen. “The study shows that overweight women can now lose weight with liraglutide without increasing the risk of losing bone mass. At the same time, they also achieve a number of other positive effects on their sugar metabolism which are not achieved through a diet-induced weight loss alone,"

The importance of intestinal hormones on bone formation and breakdown has long been a focus area and this study now opens up for exploiting the beneficial effect of intestinal hormones on the bones.

"Overweight is a protective factor for osteoporosis and bone fractures, but it increases the risk of other diseases such as cardiovascular diseases and type 2 diabetes. It appears that treatment with liraglutide makes it possible to lose weight and maintain the beneficial effect on the bones, while at the same time reducing the risk of cardiovascular disease and type 2 diabetes. This may have a significant bearing on our future approach to obesity treatment," added Torekov.

The study, GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women., has been published in the Journal of Clinical Endocrinology and Metabolism and was presented at the American Diabetes Association (ADA) in Boston on 6th June 2015.

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