Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial

Abstract

Background Several antidiabetic therapies affect bone metabolism. Sulfonylureas have the lowest impact on bone among oral antidiabetics. The objective of this study is to compare the effects of vildagliptin and gliclazide modified release (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with uncontrolled type 2 diabetes (T2D). Methods Forty-two postmenopausal women with uncontrolled T2D were randomly allocated into vildagliptin or gliclazide MR (control) groups. The primary endpoint was the change in the BTMs in months 6 and 12 compared with the baseline. The secondary endpoint was the variation in the BMD, which was assessed via dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and total hip at baseline and month 12. Results After a 12-month treatment, the BTM serum carboxy-terminal telopeptide of type 1 collagen increased 0.001 ± 0.153 ng/mL in the vildagliptin group versus 0.008 ± 0.060 ng/mL in the gliclazide MR group ( p = 0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen type I and urinary amino-terminal telopeptide of type 1 collagen remained stable in both groups, and there was no statistically significant difference between the effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD did not change in the vildagliptin or gliclazide MR groups after a 12-month treatment (0.000 ± 0.025 g/cm 2 versus −0.008 ± 0.036, respectively, p = 0.434). Furthermore, there was a similar lack of change in the femoral neck and total hip BMD values in both treatments. Conclusions Bone turnover markers and BMD remained unchanged after a 12-month treatment in both groups, which suggests that vildagliptin has the same safety profile as gliclazide MR on bone metabolism. Trial Registration ClinicalTrials.gov number NCT01679899 Electronic supplementary material The online version of this article (doi:10.1186/s13098-017-0232-2) contains supplementary material, which is available to authorized users.

Diabetes pharmacotherapy and effects on the musculoskeletal system

“…Among 1536 participants of the Cardiovascular Health Study, a longitudinal study of community‐based elderly adults, wherein approximately 10% of participants had a diagnosis of diabetes, DPP‐4 plasma activity was not associated with individual BMD or with incident hip fractures . Vildagliptin had no effects on bone markers or BMD over a 12‐month period of therapy in post‐menopausal women with T2D, although effects on fracture risk were not an endpoint of this study.…”

“…Glyburide had the smallest effect on markers of osteoblast activity (P1NP and bone alkaline phosphatase), in both women and men. Another randomized controlled trial, designed to compare the effects of one year treatment with gliclazide (modified release; 73.3 ± 25.7 mg] to a DPP‐4 inhibitor (vidagliptin, 100 mg) on bone metabolism in 42 postmenopausal women with uncontrolled T2D, found no impact of the SU on bone formation (PINP, osteocalcin) or resorption (CTX, U‐NTX) markers compared with baseline; in addition, gliclazide modified release use did not affect lumbar spine, femoral neck, or total hip BMD. Finally, a nested case‐control study, examining any association between antidiabetic treatments (alone or in combination) in a “real‐world” setting, demonstrated that the use of a SU combined with metformin modestly increased fracture risk compared with metformin alone; however, the causality for SU could not be established …”

“…However, regarding bone integrity, one BMD remained stable from baseline following 52 or 104 weeks of treatment with either of these medications 252. The risk of fracture from SUs has, to date, predominately been associated with the risk of falls due to hypoglycemia[253][254][255][256] with SU therapy, and not to a direct effect of the drugs on bone remodeling (bone turnover markers) or integrity (ie, BMD) 252,257. Because SUs increase both first and second phase insulin release by β-cells (in a glycaemia-independent manner), hypoglycemia is a known risk factor of the SUs.…”

Review article: effects of type 2 diabetes therapies on bone metabolism

“…Again, evidence from both the ADOPT study and the Rochester study indicate that glyburide, one of the class representatives, does not have an effect on bone metabolism and fracture risk [ 21 , 39 ], with exception of the decreased serum levels of the bone formation marker PINP with glyburide therapy [ 22 ]. A recent study published by our group suggests that gliclazide modified release, a sulfonylurea, does not change bone markers concentrations nor BMD [ 40 ]. The existing data support the impression that sulfonylureas have a minimal effect and are at least neutral concerning BMD and their effects regarding fractures are confounded by the hypoglycemia-induced fall risk in elderly subjects.…”

“…We previously reported a prospective trial comparing the bone effects of vildagliptin and gliclazide modified release (MR), a sulphonylurea, in a subset of postmenopausal women with T2DM. Neither drugs showed any positive or negative effects on the markers of bone formation or resorption or on BMD [ 40 ].…”