Association between incretin-related drugs and fractures in patients treated with pioglitazone: A pharmacovigilance study using the FDA Adverse Event Reporting System

Oct 22, 2025International journal of clinical pharmacology and therapeutics

Link between incretin drugs and bone fractures in patients taking pioglitazone

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Abstract

Inverse associations were observed between incretin-related drugs and fractures in patients treated with pioglitazone.

Dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may be linked to a lower incidence of fractures.
Specifically, drugs such as sitagliptin (DPP-4I) and exenatide and liraglutide (GLP-1RAs) are associated with reduced fracture risk.
A subgroup analysis indicated that GLP-1RAs, particularly exenatide and liraglutide, may further decrease fracture risk in patients taking pioglitazone.
These findings suggest a potential protective effect of incretin-related drugs on bone health in diabetic patients.

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OBJECTIVE: Diabetes mellitus (DM) causes various long-term complications and has, e.g., a direct negative effect on bone metabolism. Pioglitazone, which is used to treat DM, increases the risk of fractures. Reduced bone metabolism in patients with DM substantially impairs their quality of life. Therefore, this study aimed to determine the association of fractures with incretin-related drugs, dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients treated with pioglitazone using a pharmacovigilance database.

MATERIALS AND METHODS: Data from the U.S. Food and Drug Administration Adverse Event Reporting System from the first quarter of 2013 to the end of 2019 were analyzed. The reporting odds ratio and information component values were used to evaluate the positive and inverse associations between the abovementioned drugs and fractures.

RESULTS: Inverse associations were observed between incretin-related drugs and fractures in patients treated with DPP-4Is (sitagliptin) and GLP-1RAs (dulaglutide, exenatide, and liraglutide). A subgroup analysis revealed inverse associations between fractures and GLP-1RAs (exenatide and liraglutide) in patients treated with pioglitazone.

CONCLUSION: Our results suggest that incretin-related drugs, especially GLP-1RAs, reduce the risk of fractures in patients treated with diabetes medications such as pioglitazone.

Association between incretin-related drugs and fractures in patients treated with pioglitazone: A pharmacovigilance study using the FDA Adverse Event Reporting System

Abstract

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