Fotagliptin, potential new approach for treatment-naive patients with type 2 diabetes

There has been a marked increase in T2D prevalence with a forecasted increase to 7079 individuals per 100, 000 by 2030 from f 347 million individuals worldwide in 2008. Many guidelines have recommended metformin as a first-line therapy in combination with exercise and a healthy diet for T2DM management and provided recommendations on second-line therapies when metformin is unable to maintain or achieve long-term glycemic control. However, the selection of second-line therapies for T2DM is challenging.

Dipeptidyl peptidase-4 inhibitors (DPP-4i) could improve blood sugar control by preventing the rapid degradation of incretin hormones and inhibiting glucagon secretion. DPP4 inhibitors have become firmly established in national guidelines and treatment algorithms for improving glycemic control in type 2 diabetes mellitus

Fotagliptin (Salubris Pharmaceuticals, Shenzhen, China) is a selective, once-daily, novel DPP-4 inhibitor approved for glycemic management of T2DM. Mingtong Xu, Sun Yat-Sen University, Guangzhou, China, and colleagues report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to evaluate the safety and efficacy of fotagliptin in treatment-naive patients with T2DM.

Patients with type 2 diabetes were randomized in the ratio of 2:1:1 to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) for 24 weeks of the double-blind treatment period, followed by an open-label treatment period, totalling 52 weeks.

The study's primary efficacy endpoint was to determine fotagliptin's superiority over placebo in the HbA1c change from baseline to week 24. All serious or significant adverse events were recorded.

The study led to the following findings:

· After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo.

· Estimated mean treatment differences in HbA1c were -0.44% for fotagliptin versus placebo, -0.46% for alogliptin versus placebo, and 0.02% for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin.

· Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment.

· During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each).

· No drug-related serious adverse events were observed in any treatment group.

"Fotagliptin is a potential new approach for treating T2DM patients who are inadequately controlled with exercise and diet intervention," the researchers concluded.

Reference:

Xu, M., Sun, K., Xu, W. et al. Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial. BMC Med 21, 388 (2023). https://doi.org/10.1186/s12916-023-03089-x