Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials

Nov 27, 2024Bone

Use of Glucagon-like Peptide-1 Receptor Agonists and Bone Fracture Risk in Type 2 Diabetes

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Abstract

A total of 44 randomized controlled trials involving 47,823 patients were analyzed, revealing a pooled fracture risk reduction of 23% with GLP-1 receptor agonists compared to other treatments.

Patients treated with GLP-1 receptor agonists had a relative risk of fractures of 0.77 compared to those receiving placebo or other anti-diabetic medications.
The reduction in fracture risk was significant only for treatments lasting more than 78 weeks.
Liraglutide was specifically associated with a substantial decrease in fracture risk, with a relative risk of 0.42.
Other GLP-1 receptor agonists did not show similar benefits over other anti-diabetic drug treatments.
The findings suggest a potential link between GLP-1 receptor agonist treatment duration and fracture risk reduction in type 2 diabetes patients.

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BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporosis (OP) and fractures.

PURPOSE: The aim of this study was to analyze the available evidence on the effect of GLP-1 RAs on fracture risk in patients with type 2 diabetes.

METHODS: A systematic search based on PubMed, Embase and Web of Science databases was performed to collect relevant literature published until May 2024 on the application of GLP-1 RAs in T2DM patients. Data were extracted from each study for comparative analysis, and meta-analysis was performed using R software to calculate relative risk (RR) and 95 % confidence intervals (CI) for dichotomous variables. Two subgroup analyses were also performed.

RESULTS: A total of 44 randomized controlled trials (RCTs) involving 47,823 patients were analyzed. There were 292 incident fracture cases (138 in GLP-1 RAs group and 154 in control group). The pooled RR for fractures in patients treated with GLP-1RAs compared with those treated with placebo or other anti-diabetic drugs was 0.77 (95 % CI: 0.61-0.96). Subgroup analyses showed that the beneficial effect was dependent on the period of treatment with GLP-1 RAs, only treated for >78 weeks were effective in reducing the risk of fractures in patients with T2DM (RR 0.77; 95 % CI: 0.61-0.96). Furthermore, subgroup analyses showed that liraglutide treatment was associated with a significant reduction in fracture risk (RR 0.42; 95 % CI: 0.21-0.85). However, other GLP-1 RAs did not present benefits over other anti-diabetic drug treatments.

CONCLUSION: GLP-1 RAs could reduce the risk of fracture in T2DM patients, and the beneficial effect was interrelated to the period of treatment. Liraglutide could significantly reduce the risk of fracture in T2DM patients compared to placebo and other anti-diabetic drugs. Due to the limited nature of contemporary research, further studies are needed to develop a clear clinical consensus.

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Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials

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