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SGLT2i—especially in combination therapy—show the greatest reduction in fracture risk among patients with type 2 diabetes mellitus, followed by GLP-1 RA and DPP-4i.
As per the outcomes of a large study involving more than 1 million patients, sodium-glucose cotransporter 2 inhibitor (SGLT2i)-based therapy illustrates the most favorable bone safety profile in type 2 diabetes mellitus (T2DM) when compared with glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i).
T2DM is linked with an increased susceptibility to fractures, making drug safety a critical concern. This study compared real-world fracture risk across three key antidiabetic classes:
Researchers conducted a network meta-analysis including 13 population-based cohort studies, encompassing 1,064,952 T2DM patients. Data were sourced from major databases including Cochrane Library, Web of Science, Scopus, and PubMed. The key endpoint ascertained was the risk of total fractures, assessed across different drug classes and compared both directly and indirectly via statistical modeling.
Ranking probabilities were calculated using SUCRA and P-scores to identify the most protective therapies. All evaluated therapies were linked with a reduction in fracture risk. However, SGLT2i–based therapies ranked highest in SUCRA probability analysis, indicating the strongest likelihood of minimizing fracture risk (Table 1).
This large real-world analysis strengthens the evidence that modern glucose-lowering therapies are not only beneficial for glycemic control but may also mitigate fracture risk. Among them, SGLTi—especially in combination regimens—rank highest for skeletal safety, supporting their broader use in T2DM sufferers.
Frontiers in Endocrinology
Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies
Mohamed E A Mostafa et al.
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