Saxagliptin Hydrochloride

In high‑fat diet/streptozotocin‑induced diabetic rats, saxagliptin (a DPP‑4 inhibitor) for 12 weeks improved insulin secretion capacity (by hyperglycemic clamp) and increased β‑cell/α‑cell area ratio. It induced β‑cell proliferation (c‑myc, cyclin D1 upregulation), reduced DPP‑4 activity, restored SDF‑1α levels, and activated β‑catenin and AKT. Silencing the SDF‑1α receptor CXCR4 attenuated saxagliptin’s proliferative effect. Saxagliptin promotes β‑cell proliferation via SDF‑1α/CXCR4‑dependent activation of WNT and AKT signaling, suggesting DPP‑4 inhibitors may delay β‑cell failure.

Fig. 1 Effects of saxagliptin on body weight, blood glucose, and islet function in high-fat diet/STZ-induced diabetic rats. Body weight was measured every 2 weeks. (Li CJ, et al., 2017)

In a 24‑month, three‑arm randomized trial (301 adult‑onset autoimmune type 1 diabetes), adding saxagliptin plus vitamin D to conventional therapy (metformin ± insulin) significantly preserved β‑cell function, with a smaller decline in 2‑h C‑peptide AUC (‑276 vs. ‑419 pmol/L, P=0.01), especially in patients with higher GADA levels. Saxagliptin alone did not significantly preserve C‑peptide. Both active treatments reduced insulin dose without worsening glycemic control. Saxagliptin plus vitamin D is a promising adjunctive therapy for adult‑onset type 1 diabetes.

Fig. 2 Effects of Saxagliptin and Saxagliptin plus Vitamin D on Secondary Endpoints. (Yan X, et al., 2023)