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Patients with type 2 diabetes who were treated second-line with sodium-glucose co-transporter-2 (SGLT2) inhibitors, which can be associated with weight loss, did not have an increased risk of major osteoporotic fractures.

Compared with individuals using a sulfonylurea, those given a SGLT2 inhibitor had a fully adjusted hazard ratio for major osteoporotic fracture of only 1.2 (95% CI 0.8-1.8), reported Nikki Werkman, PharmD, of Maastricht University Medical Center in the Netherlands.

"Type 2 diabetes is a metabolic disorder associated with decreased bone quality," she said at the . The lack of glycemic control observed in patients with diabetes results in accumulation of advanced glycation end products leading to reduced bone turnover and a deterioration in the quality of bone. In spite of the fact that their bone mineral density (BMD) can be normal or elevated, they have an elevated risk for fractures.

In patients with type 2 diabetes whose blood glucose is not well controlled with diet/lifestyle measures and pharmacotherapy with metformin, second-line options include the SGLT2 inhibitors, sulfonylureas, and the incretin class of agents.

Clinical trials have demonstrated consistent reductions in glycated hemoglobin (HbA1c) with SGLT2 inhibitor therapy. Another potentially beneficial effect is the 2- to 5-kg weight loss that some patients experience while on these drugs.

"While losing weight is generally considered beneficial for patients with type 2 diabetes, we also know that a lower BMI is associated with an increased risk of osteoporotic fractures," she said.

Therefore, to investigate the association between the use of SGLT2 inhibitors, changes in BMI, and risk of major osteoporotic fractures, she and her colleagues analyzed data from the U.K. Clinical Practice Research Database, which is one of the world's largest primary care databases. It covers approximately 7% of the British population and is representative of the country's general population.

Within this cohort, the researchers identified 6,592 new users of SGLT2 inhibitors from 2013 to 2018 whose mean age was 58. Median follow-up was 2.4 years.

Mean BMI was quite high, at 36, and HbA1c control was poor, at a mean of 9%, she said. A total of 27% had a history of fractures. Those considered major were fractures of the hip, radius/ulna, and humerus, along with clinically symptomatic vertebral fractures.

The analysis was adjusted for age, sex, comorbidities, smoking, alcohol consumption, and use of other medications.

Among current users of SGLT2 inhibitors, there were 33 major osteoporotic events.

BMI loss of more than 0.5 points was seen in 15% of patients in the SGLT2 inhibitor group, and compared with sulfonylurea users, there was no increased risk for fracture in these patients (HR 1.1, 95% CI 0.6-1.9).

A few patients (<5%) actually gained 0.5 BMI points or more; they also had no increased fracture risk (HR 1.3, 95% CI 0.5-3.6), nor did the remainder of patients whose weight remained stable (HR 1.3, 95% CI 0.7-2.2).

"In summary, our main finding was that there was no association between the use of SGLT2 inhibitors, changes in BMI, and the risk of osteoporotic fracture," she concluded.

Strengths of the study included its population-based design and statistical adjustment for a wide range of potential confounders, while a limitation was its relatively young patient sample. "As a result of this, we observed lower fracture rates than we probably would have had in an elderly population," she noted.

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