Clinical guidelines recommend denosumab for people with osteoporosis at high risk of fracture. Denosumab has potent effects in suppressing bone resorption, and observational studies and post hoc analyses of randomized trials suggest it also has beneficial effects on glucose metabolism.

Now, researchers at Brigham and Women’s Hospital have associated denosumab use with a 32% decreased risk of type 2 diabetes compared with the use of an oral bisphosphonate. Daniel H. Solomon, MD, MPH, a rheumatologist in the Division of Rheumatology, Inflammation and Immunity at the Brigham, Houchen Lyu, MD, of the Chinese PLA General Hospital, and colleagues published the findings in The BMJ.

Background

Many pharmacoepidemiologists have begun to recommend using the “new user” design for retrospective observational studies, a way to approximate a randomized, controlled trial. These studies analyze a cohort from treatment initiation, including patients’ pretreatment characteristics, and capture all events during follow-up.

In real-world practice, most patients use other anti-osteoporosis drugs before switching to denosumab. Therefore, the Brigham group modified the new user design by including both treatment-naïve participants and those who switched to denosumab from an oral bisphosphonate.

Methods

The data source for the study was the IQVIA Medical Research Data, which captures primary care records from more than 800 general practitioners in the U.K. The research team identified 4,301 patients who became new users of denosumab 60 mg between July 1, 2010, and December 31, 2021, and met certain other criteria.

By considering a number of risk factors for diabetes, the researchers created propensity scores and matched each of the 4,301 patients with five patients who used an oral bisphosphonate (alendronate 10 or 70 mg, ibandronate 150 mg, or risedronate 35 mg).

Treatment-naïve denosumab users were matched with new bisphosphonate users. Patients who switched to denosumab from a bisphosphonate were matched with patients who had used a bisphosphonate for an equal length of time and were continuing use.

Primary Analysis

The primary outcome was incident type 2 diabetes as defined by diagnostic codes. Over five years of follow-up, the incidence was:

• Bisphosphonate users—8.3 per 1000 person-years
• Denosumab users—5.7 per 1000 person-years (HR, 0.68; 95% CI, 0.52–0.89)

Subgroup Analyses

People at high risk of diabetes because of prediabetes or obesity showed even greater reductions in risk. The incidence of diabetes was the following:

Among people with prediabetes

• Bisphosphonate—22.1 per 1,000 person-years
• Denosumab—11.8 per 1,000 person-years (HR, 0.54; 95% CI, 0.35–0.82)

Among people with obesity

• Bisphosphonate—24.7 per 1,000 person-years
• Denosumab—16.2 per 1,000 person-years (HR, 0.65; 95% CI, 0.40–1.06)

Individualized Management of Osteoporosis

People with osteoporosis who are at high risk of type 2 diabetes, especially those with prediabetes or obesity, should be advised the risk might be reduced with denosumab compared with the use of an oral bisphosphonate.