A new study published in the journalBMC Medicineshowed that sitagliptin treatment helped preserve total femur T scores in women with type 2 diabetes compared to placebo, which suggest a protective effect on bone health. Dipeptidyl peptidase-4 inhibitors (DPP4-Is) may preserve bone, according to experimental models, although there is a lack of clinical evidence and randomized studies that focus on bone outcomes. This trial was set to assess the safety and effectiveness of oral sitagliptin therapy for 52 weeks in enhancing bone outcomes in women with type 2 diabetes. A total of 132 women with type 2 diabetes who were receiving metformin monotherapy and stable glycemic control were included in this study. The participants were chosen at random to receive sitagliptin or a placebo for 52 weeks after being sourced from diabetes outpatient clinics at Sapienza University in Rome, Italy. Changes in bone turnover biomarkers and bone mineral density (BMD) were the primary results. Per-protocol (PP) and intention-to-treat (ITT) analyses were performed. Over the course of 52 weeks, sitagliptin treatment maintained the total proximal femur BMD T score (estimated mean difference: −0.02; 95% CI: − 0.07; 0.03; p = 0.46), while the placebo group experienced a significant decrease (estimated mean difference: − 0.13; 95% CI: − 0.19; p < 0.0001). There was a significant difference between the groups in favor of sitagliptin (estimated mean difference: 0.11; 95% CI: 0.03; 0.19; p = 0.0063). Other skeletal locations and bone turnover indicators showed no discernible changes. The findings from the ITT analysis were validated by the PP analysis. Sitagliptin dramatically decreased the levels of inflammatory mediators involved in bone metabolism as compared to the placebo. At 52 weeks, there were no documented variations in glucose control between or among groups. 5 mild to moderate adverse events occurred, evenly split between the groups, where no significant adverse events were observed. Overall, without consistently affecting turnover indicators or other bone locations, sitagliptin medication was linked to the preservation of the total hip T score in women with type 2 diabetes. Barchetta, I., Filardi, T., Dule, S., Cimini, F. A., Sentinelli, F., Romagnoli, E., Passarella, G., Bleve, E., Oldani, A., Venditti, V., Anastasi, E., Gandini, O., Napoli, N., Nicolucci, A., Lenzi, A., Baroni, M. G., Morano, S., Cavallo, M. G., & SlowDOWN Study Network. (2025). Effect of sitagliptin vs. placebo on bone mineralization in women with type 2 diabetes: the SLowDOWN (SitagLiptin in Diabetes for Osteoporosis in WomeN) randomized clinical trial. BMC Medicine, 23(1), 562.https://doi.org/10.1186/s12916-025-04363-w