In the Journals

No increased fracture risk with real-world use of antidiabetes therapies

In an analysis of real-world data, the use of SGLT2 inhibitors, GLP-1 receptor agonists and DPP-IV inhibitors were not associated with an increased risk for fracture in adults with type 2 diabetes, according to findings published in Osteoporosis International.

Khemayanto Hidayat

“The cumulative evidence from observational studies suggests that bone fracture is not a major concern for patients with type 2 diabetes, patients taking DPP-IV inhibitors, GLP-1 receptor agonists or SGLT2 inhibitors in routine clinical practice,” Khemayanto Hidayat, MBBS, MD, a research fellow in the department of endocrinology and metabolism at the First Affiliated Hospital of Soochow University, China, told Endocrine Today. “These findings further support the lack of an association between the use of DPP-IV inhibitors, GLP-1 receptor agonists or SGLT2 inhibitors and the risk for fracture that have been reported by several meta-analyses of randomized controlled trials. Further studies need to investigate the long-term impact of these drugs on fracture risk, particularly in high-risk populations.”

In a meta-analysis, Hidayat and colleagues analyzed data from 18 cohort or case-control studies assessing an association between DPP-IV inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists and fracture risk in type 2 diabetes (14 cohort studies; four case-control studies). All data regarding participant characteristics, medications and diagnoses were identified via databases or registries. Researchers used a random-effects model to estimate summary relative risks for the association between the antidiabetes therapies and fracture risk.

Across 11 studies assessing the use of DPP-IV inhibitors and fracture risk, researchers observed no increased risk vs. comparators (RR = 0.83; 95% CI, 0.6-1.14). The findings were similar for four studies assessing the use of GLP-1 receptor agonists (RR = 0.65; 95% CI, 0.24-1.74) and four studies assessing risk associated with SGLT2 inhibitors (RR = 1.02; 95% CI, 0.91-1.16).

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The use of SGLT2 inhibitors, GLP-1 receptor agonists and DPP-IV inhibitors were not associated with an increased risk for fracture in adults with type 2 diabetes.
Adobe Stock

Researchers noted that the lack of association between the use of DPP-IV inhibitors or GLP-1 receptor agonists and the risk for fracture persisted across nearly all subgroups, apart from an observed reduced risk for hip fracture with GLP-1 receptor agonist use (RR = 0.21; 95% CI, 0.04-0.98). However, the reduced risk did not persist after the exclusion of one study that demonstrated a strong inverse association, according to researchers.

“Our findings, together with the cumulative evidence from randomized controlled trials, should reassure policymakers and medical practitioners that the use of these medications is unlikely to increase the risk of fracture among type 2 diabetes patients in general,” Hidayat said.

In 2015, the FDA warned that the SGLT2 inhibitor canagliflozin (Invokana, Janssen) may cause an increased risk for bone fractures. As Endocrine Today reported at the time, the FDA said patients should not change or stop their medications without talking to their physician, and that the agency was continuing to examine other drugs in the class. – by Regina Schaffer

For more information:

Khemayanto Hidayat, MBBS, MD, can be reached at the First Affiliated Hospital of Soochow University, No. 188 Shizi St., Suzhou 215006, China; email: khemzie_khem@yahoo.com.

Disclosures: The authors report no relevant financial disclosures.

In an analysis of real-world data, the use of SGLT2 inhibitors, GLP-1 receptor agonists and DPP-IV inhibitors were not associated with an increased risk for fracture in adults with type 2 diabetes, according to findings published in Osteoporosis International.

Khemayanto Hidayat

“The cumulative evidence from observational studies suggests that bone fracture is not a major concern for patients with type 2 diabetes, patients taking DPP-IV inhibitors, GLP-1 receptor agonists or SGLT2 inhibitors in routine clinical practice,” Khemayanto Hidayat, MBBS, MD, a research fellow in the department of endocrinology and metabolism at the First Affiliated Hospital of Soochow University, China, told Endocrine Today. “These findings further support the lack of an association between the use of DPP-IV inhibitors, GLP-1 receptor agonists or SGLT2 inhibitors and the risk for fracture that have been reported by several meta-analyses of randomized controlled trials. Further studies need to investigate the long-term impact of these drugs on fracture risk, particularly in high-risk populations.”

In a meta-analysis, Hidayat and colleagues analyzed data from 18 cohort or case-control studies assessing an association between DPP-IV inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists and fracture risk in type 2 diabetes (14 cohort studies; four case-control studies). All data regarding participant characteristics, medications and diagnoses were identified via databases or registries. Researchers used a random-effects model to estimate summary relative risks for the association between the antidiabetes therapies and fracture risk.

Across 11 studies assessing the use of DPP-IV inhibitors and fracture risk, researchers observed no increased risk vs. comparators (RR = 0.83; 95% CI, 0.6-1.14). The findings were similar for four studies assessing the use of GLP-1 receptor agonists (RR = 0.65; 95% CI, 0.24-1.74) and four studies assessing risk associated with SGLT2 inhibitors (RR = 1.02; 95% CI, 0.91-1.16).

#
The use of SGLT2 inhibitors, GLP-1 receptor agonists and DPP-IV inhibitors were not associated with an increased risk for fracture in adults with type 2 diabetes.
Adobe Stock

Researchers noted that the lack of association between the use of DPP-IV inhibitors or GLP-1 receptor agonists and the risk for fracture persisted across nearly all subgroups, apart from an observed reduced risk for hip fracture with GLP-1 receptor agonist use (RR = 0.21; 95% CI, 0.04-0.98). However, the reduced risk did not persist after the exclusion of one study that demonstrated a strong inverse association, according to researchers.

“Our findings, together with the cumulative evidence from randomized controlled trials, should reassure policymakers and medical practitioners that the use of these medications is unlikely to increase the risk of fracture among type 2 diabetes patients in general,” Hidayat said.

In 2015, the FDA warned that the SGLT2 inhibitor canagliflozin (Invokana, Janssen) may cause an increased risk for bone fractures. As Endocrine Today reported at the time, the FDA said patients should not change or stop their medications without talking to their physician, and that the agency was continuing to examine other drugs in the class. – by Regina Schaffer

For more information:

Khemayanto Hidayat, MBBS, MD, can be reached at the First Affiliated Hospital of Soochow University, No. 188 Shizi St., Suzhou 215006, China; email: khemzie_khem@yahoo.com.

Disclosures: The authors report no relevant financial disclosures.