Mizagliflozin
SGLT1 is an glucose transporter that is present in the gastrointestinal (GI) tract. It is responsible for transporting nutritional glucose from the intestine into the bloodstream.
Mizagliflozin is a small molecule inhibitor of SGLT1 that is minimally absorbed in the body. This results in limiting mizagliflozin’ s primary site of action to the GI tract.
In two Phase 1 clinical studies in healthy subjects, mizagliflozin has been shown to reduce and delay glucose absorption and prevent postprandial spikes in plasma insulin. In the first Phase 1 study, increasing single doses of mizagliflozin or placebo were administered immediately prior to breakfast. Plasma glucose and insulin concentrations were determined at various times up to six hours after dosing. Compared to placebo, single doses of mizagliflozin reduced the increase in postprandial blood glucose levels and delayed time to peak concentrations. These effects were dose-dependent. The inhibitory effect on blood glucose increases was most pronounced one hour after the meal. In addition, insulin exhibited a profile similar to that of blood glucose levels with a dose dependent suppression of insulin concentrations that was most pronounced one hour after a meal.
In the second Phase 1 study, healthy subjects received placebo or mizagliflozin three times a day (TID) for 10 days. A control group dosed TID with 50 mg miglitol (an alpha-glucosidase inhibitor) was also included. Postprandial effects were determined after breakfast, lunch and dinner on Day 3 and Day 12. For all doses studied, mizagliflozin reduced the increase of postprandial plasma glucose and insulin concentrations after each meal.
The data from these two Phase 1 studies in healthy subjects are consistent with the desired effect on postprandial glucose and insulin levels and provide strong support for mizagliflozin as a therapeutic candidate to treat patients with PBH.
In 2022 Vogenx initiated a phase 2 clinical study to determine the effects of mizagliflozin in patients with PBH (NCT05541939). The single ascending dose study in PBH patients measured the effect of mizagliflozin on safety and tolerability, and levels of circulating postprandial glucose and insulin. Results from this study demonstrated significant improvement in glucose nadir and glucose peak, as well as peak insulin. Results of the study were presented at the annual meeting of the Endocrinology Society in June 2023.
A phase 2 dose and regimen ranging clinical study of mizagliflozin in patients diagnosed with PBH is ongoing with results expected to be available in the first half of 2024.