OBJECTIVES: Type 2 diabetes mellitus (T2DM) affects bone metabolism and increased risk of fracture among elderly population. There is no consensus on the selection of specific drug therapies when metformin not adequately responsive in T2DM. Evidence from the published clinical studies suggested inconclusive results regarding effect of anti-diabetic medications on the fracture risk. Therefore, this study aimed to determine effect of DPP-4 Inhibitors compared to sulfonylureas as add-on therapy to metformin in inadequately controlled patients with T2DM.

METHODS: A systematic literature search on PubMed/Medline was conducted to identify randomized controlled trials (RCTs) in patients with T2DM. RCTs comparing DPP-4 Inhibitors versus sulfonylureas as add-on therapy to metformin in T2DM patients were included. We calculated Peto odd ratio with 95% confidence interval (CI) with fixed effect model to compare DPP-4 Inhibitors versus sulfonylureas as add-on therapy to metformin. Meta-analysis was performed by using RevMan 5.3 software.

RESULTS: A total 7 RCTs including 8584 patients with 48 fracture cases. From the included studies patient age, fasting blood glucose level, HbA1c, BMI, and duration of diabetes were ranged from 54.30-72.60 years, 8.9-9.2 mmol/L, 7.5-8.1%, 30-32.5 kg/m², and 5.5-7.6 years respectively. Duration of trials were ranged from 30-104 weeks. Results from meta-analysis showed a non-significant association between overall risk of fracture and DPP-4 inhibitors compared to sulfonylureas as add-on therapy to metformin in inadequately controlled patients with T2DM (Peto odd ratio: 1.45, 95%CI: 0.82-2.57; p=0.21). There was no significant heterogeneity amongst the studies (I²=0%; p=0.86).

CONCLUSIONS: The current result suggests no detrimental effect of DPP-4 inhibitors on fractures risk compared to sulfonylureas in patients with T2DM. The DPP-4 inhibitors and sulfonylureas can be considered as options for add-on therapy to metformin in inadequately controlled T2DM patients. Further long term follow-up RCTs and real world studies are required to confirm the current findings.