Perspectives on Diabetes Care

Another Use for GLP-1 Receptor Agonists?

Jun 10, 2015, 20:00 PM

There are currently five approved GLP-1 receptor agonists (GLP-1 RA) available in the United States. There is one short-acting agent, exenatide immediate-release or Byetta. There are four long-acting agents, liraglutide (Victoza), exenatide extended-release (Bydureon), albiglutide (Tanzeum) and dulaglutide (Trulicity). There are other emerging GLP-1 RA being investigated. GLP-1 RA are effective in reducing hemoglobin A1C, fasting glucose and post-prandial glucose levels. These agents have also been shown to reduce weight from baseline over 6 to 12 months. Some of the trials reported statistically significant improvements in systolic blood pressure and cholesterol levels with a specific GLP-1 RA. Overall, these agents have several benefits for patients with diabetes.

Recently, a study was published in the Journal of Clinical Endocrinology and Metabolism about the effect of liraglutide on bone mineral content and density among women. In this study, biomarkers for bone formation and resorption were also evaluated. In the study, individuals were recruited if s/he were 18 to 65 years of age and had a body mass index between 30 to 40 kg/m2. Prior to randomization, individuals had to follow an 8-week weight loss program and lose 7.5% of body weight from baseline. This program included a low-calorie diet of amino acids, fatty acids, vitamins and minerals. After 8 weeks, 37 women were randomized to either liraglutide 1.2 mg per day or a control group for a total of 52 weeks. Among the liraglutide-treated group, bone mineral content and density were maintained, whereas bone mineral content was lost among individuals in the control group. The biomarker for bone formation (i.e. P1NP) increased among the liraglutide-treated group, which was a statistically significant result versus placebo. There were no other changes in biomarkers from either group.

While this trial provides new evidence with GLP-1 RA that I have discovered, there are some limitations, such as small sample size and short duration. In addition, the authors did not report if the women had prediabetes or diabetes.  Only BMI and body weight were reported as baseline characteristics. The most significant amount of weight loss occurred during the “pre-trial” 8-week program, but weight was maintained through the intervention period with liraglutide and the control. In addition, the addition of a GLP-1 RA did not change vitamin D levels. It is important to note that none of the women had vitamin D deficiency, as the levels were above 30  ng/mL at baseline and prior to randomization. More evidence would be added to the current literature of anti-hyperglycemic agents and effect on osteoporosis. For example, rosiglitazone has been associated with increased risk of fractures and it is unknown if SGLT-2 inhibitors have an impact on osteoporosis. Therefore, this trial may be the start of new evidence regarding GLP-1 RA among a special patient population. Interesting stuff!