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Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials.

Monami M, Dicembrini I, Antenore A, Mannucci E - Diabetes Care (2011)

Bottom Line: Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients.Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.

View Article: PubMed Central - PubMed

Affiliation: Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, Careggi Teaching Hospital, Florence, Italy.

ABSTRACT

Objective: Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients. Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.

Research design and methods: A meta-analysis was performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP-4 inhibitors with placebo or active drugs.

Results: Twenty-eight trials enrolling 11,880 and 9,175 patients for DPP-4 inhibitors and comparators, respectively, were included, reporting 63 fractures. DPP-4 inhibitors, compared with placebo or other treatments, were associated with a reduced risk of fractures (Mantel-Haenszel odds ratio [MH-OR] 0.60, 95% CI 0.37-0.99, P = 0.045), even after the exclusion of comparisons with thiazolidinediones or sulfonylureas (MH-OR 0.56, 0.33-0.93, P = 0.026).

Conclusions: The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.

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Related in: MedlinePlus

Subgroup analyses of MH-OR (95% CI) for bone fractures in placebo-controlled trials. DPP-4i, DPP-4 inhibitors.
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Figure 1: Subgroup analyses of MH-OR (95% CI) for bone fractures in placebo-controlled trials. DPP-4i, DPP-4 inhibitors.

Mentions: The total number of bone fractures was 63 (26 and 37 with DPP-4 inhibitors and comparators, respectively). The MH-OR for DPP-4 inhibitors was 0.60 (95% CI 0.37–0.99, P = 0.045) (Supplementary Fig. A3); the corresponding figure with continuity correction was 0.60 (0.39–0.92, P = 0.019). The MH-OR for DPP-4 inhibitors was 0.54 (0.28–1.03, P = 0.063) and 0.70 (0.32–1.52, P = 0.37) in trials with a duration <52 weeks or ≥52 weeks, respectively; only 7 trials with events and duration ≥52 weeks were available. Similar results (MH-OR 0.41, 0.21–0.81, P = 0.01) were obtained in placebo-controlled trials, with no difference across individual DPP-4 inhibitors (Fig. 1).


Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials.

Monami M, Dicembrini I, Antenore A, Mannucci E - Diabetes Care (2011)

Subgroup analyses of MH-OR (95% CI) for bone fractures in placebo-controlled trials. DPP-4i, DPP-4 inhibitors.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198283&req=5

Figure 1: Subgroup analyses of MH-OR (95% CI) for bone fractures in placebo-controlled trials. DPP-4i, DPP-4 inhibitors.
Mentions: The total number of bone fractures was 63 (26 and 37 with DPP-4 inhibitors and comparators, respectively). The MH-OR for DPP-4 inhibitors was 0.60 (95% CI 0.37–0.99, P = 0.045) (Supplementary Fig. A3); the corresponding figure with continuity correction was 0.60 (0.39–0.92, P = 0.019). The MH-OR for DPP-4 inhibitors was 0.54 (0.28–1.03, P = 0.063) and 0.70 (0.32–1.52, P = 0.37) in trials with a duration <52 weeks or ≥52 weeks, respectively; only 7 trials with events and duration ≥52 weeks were available. Similar results (MH-OR 0.41, 0.21–0.81, P = 0.01) were obtained in placebo-controlled trials, with no difference across individual DPP-4 inhibitors (Fig. 1).

Bottom Line: Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients.Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.

View Article: PubMed Central - PubMed

Affiliation: Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, Careggi Teaching Hospital, Florence, Italy.

ABSTRACT

Objective: Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients. Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.

Research design and methods: A meta-analysis was performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP-4 inhibitors with placebo or active drugs.

Results: Twenty-eight trials enrolling 11,880 and 9,175 patients for DPP-4 inhibitors and comparators, respectively, were included, reporting 63 fractures. DPP-4 inhibitors, compared with placebo or other treatments, were associated with a reduced risk of fractures (Mantel-Haenszel odds ratio [MH-OR] 0.60, 95% CI 0.37-0.99, P = 0.045), even after the exclusion of comparisons with thiazolidinediones or sulfonylureas (MH-OR 0.56, 0.33-0.93, P = 0.026).

Conclusions: The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.

Show MeSH
Related in: MedlinePlus