SGLT2 Inhibitors for Diabetes: No Link to Fractures in Older Adults

The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does now no longer seem to elevate the hazard for fractures in older adults, new studies suggest.

The statistics come from a national propensity score-matched examination of US Medicare recipients with kind 2 diabetes who have been new customers of both an SGLT2 inhibitor, a dipeptidyl peptidase four (DPP-four) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors became now no longer related to an extended hazard of nontraumatic fractures as compared with DPP-four inhibitors or GLP-1 agonists. Results have been steady throughout classes of sex, frailty, age, and insulin use,” said Min Zhuo, MD, of Harvard Medical School, Boston, Massachusetts, and colleagues, who posted their paintings online October 27 in JAMA Network Open.

“Our outcomes upload to the proof base comparing the protection profile of SGLT2 inhibitors in older adults outdoor of [randomized controlled trials] and in addition signify the hazard-advantage stability of SGLT2 inhibitors in scientific practice,” they write.

Asked to comment, Simeon I. Taylor, MD, Ph.D., advised Medscape Medical News, “This is an amazing examine this is typically reassuring that extraordinarily short, much less than 1 yr, remedy with an SGLT2 inhibitor does now no longer seem to noticeably boom the hazard of bone fractures.”

However, Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, additionally noted: “Notwithstanding those reassuring statistics, the paper additionally does an awesome process of stating vital limitations.”

“Most importantly, those statistics do now no longer deal with questions associated with the hazard of long-time period persistent remedy. It is instructive to refer again to the posted statistics demonstrating an about 2-yr lag earlier than a full-size boom withinside the hazard of fracture became found in rosiglitazone-handled sufferers withinside the ADOPT examine.

The duration of the lag is probably associated with the baseline bone mineral density at the time drug remedy is initiated. These issues may also contribute to the found version in bone-associated results in exceptional research.”

Concern approximately SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS examine, wherein the general fracture hazard with canagliflozin became a full-size 26% better than placebo. However, next to large randomized trials of canagliflozin and different SGLT2 inhibitors did now no longer locate the equal hazard.

In addition, preceding observational research in more youthful adults have additionally now no longer observed use of SGLT2 inhibitors to be related to extended fracture hazard as compared with DPP-four inhibitors or GLP-1 agonists.

Understanding Fracture Risk With SGLT2 Inhibitors Is “Critical”

Older adults with kind 2 diabetes may also advantage from discounts in atherosclerotic cardiovascular occasions, hospitalization for coronary heart failure, end-degree kidney disease, and loss of life-related to SGLT2 inhibitors, however, the reality that aging may also have terrible results on bone metabolism means “expertise the fracture hazard related to SGLT2 inhibitors in older adults with kind 2 diabetes is critical,” said Zhuo and colleagues.

In the cutting-edge examination, they analyzed claims statistics for Medicare beneficiaries elderly sixty-six years and older (1 yr beyond Medicare eligibility) who have been newly prescribed an SGLT2 inhibitor, DPP-four inhibitor, or GLP-1 agonist among April 1, 2013, and December 31, 2017.

A general of 45,889 sufferers from every remedy institution has been propensity-matched the usage of fifty-eight baseline characteristics, for a complete of 137,667 sufferers.

After matching, there have been 501 occasions of the number one composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By remedy institution, fracture quotes according to one thousand person-years have been four.69, 5.26, and four. seventy-one for SGLT2 inhibitors, DPP-four inhibitors, and GLP-1 agonists, respectively.

The variations among sufferers taking DPP-four inhibitors or GLP-1 agonists as compared with SGLT2 inhibitors have been now no longer full-size, with danger ratios of 0. ninety and 1.00, respectively.

Results remained steady in diverse sensitivity and subgroup analyses, together with restricting the statistics to simply the canagliflozin institution. Overall, the fracture price became extra with woman sex, frailty, older age, and insulin use, steady throughout drug classes.

The dangers for falls and hypoglycemia have been decreasing withinside the SGLT2 inhibitor as opposed to matched DPP-four inhibitor groups (danger ratio [HR], 0.82), and there has been no distinction in syncope. None of these variations have been full-size for the SGLT2 inhibitor institution as compared with the GLP-1 agonist institution.

Consistent with preceding statistics, the hazard for diabetic ketoacidosis became better with SGLT2 inhibitors as opposed to DPP-four inhibitors and GLP-1 agonists (HR, 1.29 and 1. fifty-eight), and the hazard for coronary heart failure hospitalization became decrease (HR, 0. forty-two and 0.69).

In the cutting-edge examination, they analyzed claims statistics for Medicare beneficiaries elderly sixty-six years and older (1 yr beyond Medicare eligibility) who have been newly prescribed an SGLT2 inhibitor, DPP-four inhibitor, or GLP-1 agonist among April 1, 2013, and December 31, 2017.

A general of 45,889 sufferers from every remedy institution has been propensity-matched the usage of fifty-eight baseline characteristics, for a complete of 137,667 sufferers.

After matching, there have been 501 occasions of the number one composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By remedy institution, fracture quotes according to one thousand person-years have been four.69, 5.26, and four. seventy-one for SGLT2 inhibitors, DPP-four inhibitors, and GLP-1 agonists, respectively.

The variations among sufferers taking DPP-four inhibitors or GLP-1 agonists as compared with SGLT2 inhibitors have been now no longer full-size, with danger ratios of 0. ninety and 1.00, respectively.

Results remained steady in diverse sensitivity and subgroup analyses, together with restricting the statistics to simply the canagliflozin institution. Overall, the fracture price became extra with woman sex, frailty, older age, and insulin use, steady throughout drug classes.

The dangers for falls and hypoglycemia have been decreasing withinside the SGLT2 inhibitor as opposed to matched DPP-four inhibitor groups (danger ratio [HR], 0.82), and there has been no distinction in syncope. None of these variations have been full-size for the SGLT2 inhibitor institution as compared with the GLP-1 agonist institution.

Consistent with preceding statistics, the hazard for diabetic ketoacidosis became better with SGLT2 inhibitors as opposed to DPP-four inhibitors and GLP-1 agonists (HR, 1.29 and 1. fifty-eight), and the hazard for coronary heart failure hospitalization became decrease (HR, 0. forty-two and 0.69).

In the cutting-edge examination, they analyzed claims statistics for Medicare beneficiaries elderly sixty-six years and older (1 yr beyond Medicare eligibility) who have been newly prescribed an SGLT2 inhibitor, DPP-four inhibitor, or GLP-1 agonist among April 1, 2013, and December 31, 2017.

A general of 45,889 sufferers from every remedy institution has been propensity-matched the usage of fifty-eight baseline characteristics, for a complete of 137,667 sufferers.

After matching, there have been 501 occasions of the number one composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By remedy institution, fracture quotes according to one thousand person-years have been four.69, 5.26, and four. seventy-one for SGLT2 inhibitors, DPP-four inhibitors, and GLP-1 agonists, respectively.

The variations among sufferers taking DPP-four inhibitors or GLP-1 agonists as compared with SGLT2 inhibitors have been now no longer full-size, with danger ratios of 0. ninety and 1.00, respectively.

Results remained steady in diverse sensitivity and subgroup analyses, together with restricting the statistics to simply the canagliflozin institution. Overall, the fracture price became extra with woman sex, frailty, older age, and insulin use, steady throughout drug classes.

The dangers for falls and hypoglycemia have been decreasing withinside the SGLT2 inhibitor as opposed to matched DPP-four inhibitor groups (danger ratio [HR], 0.82), and there has been no distinction in syncope. None of these variations have been full-size for the SGLT2 inhibitor institution as compared with the GLP-1 agonist institution.

Consistent with preceding statistics, the hazard for diabetic ketoacidosis became better with SGLT2 inhibitors as opposed to DPP-four inhibitors and GLP-1 agonists (HR, 1.29 and 1. fifty-eight), and the hazard for coronary heart failure hospitalization became decrease (HR, 0. forty-two and 0.69).

https://www.medscape.com/viewarticle/961683?src=#vp_2

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