Liraglutide lowers risk for amputation: investigators find patients treated with GLP-1 drug had significantly lower number of amputations compared to placebo group.
The word may still be out on whether certain oral diabetes medications puts patients at risk for lower limb complications, but a new study has shown that liraglutide is not one of them. A post hoc review analysis of the LEADER trial published in Diabetes Care examined the effects of Liraglutide on rates of foot ulceration and amputation in patients at high risk for cardiovascular (CV) events.
Liraglutide, a GLP-1 agonist, is an injectable glucose-lowering medication used in patients with type 2 diabetes. GLP-1 agonists act by mimicking the effects of the hormone GLP-1, which increases insulin secretion and lowers glucagon release. This, in effect, causes increased satiety and slowed gastric emptying, with one of the main benefits of GLP-1 agonists being weight loss in patients with diabetes.
Researchers in the present study pulled data from the LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results), a randomized double-blind controlled trial during which patients with type 2 diabetes and risk for CV events were assigned to either liraglutide or placebo groups. The treatment group received 1.8mg/day of liraglutide and was compared to a controlled placebo group.
During analysis, patients were classified as having a diabetic foot ulcer (DFU) if they reported a new onset DFU or worsening of an existing DFU. Amputation was categorized as minor (midtarsal or distal amputation), major (any resection proximal to the midtarsal level), or unknown (could not be classified as minor or major based on available data).
A total of 4,668 participants were randomized into the liraglutide group and 4,672 participants into the placebo group. Participants were followed for a median duration of 3.8 years. Hazard ratios were calculated using Cox regression model and incidence of events was estimated using the Aalen-Johansen method.
Overall, there were 260 DFU events that occurred in 176 patients in the liraglutide group, and 291 events that occurred in 191 patients in the placebo group. When examining the time to first DFU event and mean number of DFUs, although both were slightly less in the liraglutide group compared to placebo, no significant difference was found (p=0.41, p=0.76, respectively).
When examining DFU-related amputations, however, investigators found that patients treated with liraglutide had a significantly lower number of amputations compared to the placebo group. Cox regression analysis showed a statistically significant risk reduction in amputations with liraglutide (p = 0.028).
Based on results from the post hoc analysis, it was shown that patients with type 2 diabetes and a high risk of CV events were at no greater risk for developing DFUs compared to patients taking placebo. Investigators did note, however, that patients taking liraglutide were at a significantly lower risk for amputations relating to DFUs than patients on placebo.
With growing concern over diabetes-related complications, this knowledge provides tremendous opportunity for GLP-1 agonists to play a larger role in specific patient populations. Foot ulcers and other lower limb complications are a significant burden on the diabetes community. Further investigation of the claims made in this study are necessary, but provide compelling evidence for future research.
- Treatment with liraglutide was not associated with an increased risk of developing or worsening diabetic foot ulcers compared with placebo in patients with type 2 diabetes and risk for CV events.
- Liraglutide treatment significantly lowered the risk for lower limb amputation in patients with type 2 diabetes and risk for CV events.
- Additional research is needed in a broader patient population regarding liraglutide and lowered risk for amputation.
Morales, S. (2007). GLP-1 Receptor Agonists. Retrieved from https://www.diabetesdaily.com/learn-about-diabetes/overview-of-diabetes-drugs/glp-1-receptor-agonists/
Bain, S. C., Buse, J. B., Simpson, R., Tarnow, L., Kaltoft, M. S., Stellfeld, M., Ketan Dhatariya. (2018, August 02). The Impact of Liraglutide on Diabetes-Related Foot Ulceration and Associated Complications in Patients with Type 2 Diabetes at High Risk for Cardiovascular Events: Results From the LEADER Trial. Retrieved from http://care.diabetesjournals.org/content/early/2018/07/30/dc18-1094
Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy
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