In this study, the effects of sitagliptin analogue (SITA) or pioglitazone (PIO) treatment on glucose homeostasis and ${eta}$-cell dynamics in animal models of type 2 diabetes-Akita and db/db mice were evaluated. After 4-6 weeks of treatment, both SITA and PIO were shown to lower non-fasting glucose levels and reduced glycemic excursion in the intraperitoneal glucose tolerance test. In addition, both drugs preserved normal islet structure and the proportion of ${eta}$-cells in the islets. Compared to the controls, SITA treatment induced a higher ${eta}$-cell proliferation rate in Akita mice and a lower rate of apoptosis in db/db mice, whereas PIO treatment induced a lower rate of apoptosis in db/db mice and reduced proliferation rates in Akita mice. In conclusion, both SITA and PIO appear to exert some beneficial effects on the islet structure in addition to glycemic control via different mechanisms that involve ${eta}$-cell dynamics in Akita and db/db mice.