Pharmacokinetics and pharmacodynamics of rongliflozin, a novel selective inhibitor of sodium‐glucose co‐transporter‐2, in people with type 2 diabetes mellitus

Abstract

Aims To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of rongliflozin in a cohort of healthy Chinese people and people with type 2 diabetes mellitus (T2DM). Materials and methods We examined the effects of a single ascending dose (SAD) of rongliflozin (10‐200 mg) in combination with food (20 mg) in 50 healthy people, and a multiple ascending dose (MAD) of rongliflozin (10‐50 mg once daily for 12 days) in 36 people with T2DM. Results No serious adverse events (AEs) or discontinuations as a result of AEs (related to rongliflozin) occurred in either study. In healthy participants and those with T2DM, rongliflozin was rapidly absorbed, with a time to maximum plasma concentration of 0.63 to 1.75 hours. Systemic exposure (maximum observed serum concentration and area under the curve) to rongliflozin and its inactive major metabolites (T1444, T1454 and T1830) increased in proportion to dose. In the SAD and MAD studies, there was a dose‐related increase in urinary glucose excretion (UGE) ranging from 10 to 50 mg rongliflozin. This increase in UGE was associated with dose‐related decreases in serum glucose values in people with T2DM in the MAD group. In the SAD group, UGE plateaued at 50 to 200 mg. Conclusions Rongliflozin was well tolerated in all participants. The PK and PD measurements obtained for rongliflozin demonstrate a dose‐response relationship when the drug is administered at doses ranging from 10 to 50 mg in healthy people and in people with T2DM.

Pharmacokinetics, pharmacodynamics and tolerability of single and multiple doses of janagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, in Chinese people with type 2 diabetes mellitus

“…: CTR20180427). Similar findings have been reported for other SGLT2 inhibitors, including dapagliflozin, empagliflozin and rongliflozin. 24,27,28 …”

“…23,24 At dapagliflozin, empagliflozin and rongliflozin. 24,27,28 At steady state, FPG was dramatically decreased in participants with T2DM treated with janagliflozin or dapagliflozin compared to placebo. Changes in FPG after multiple oral doses of janagliflozin 25 mg and 50 mg or dapagliflozin 10 mg were similar to those reported for dapagliflozin 16 and empagliflozin.…”

Safety, pharmacokinetics and pharmacodynamics of TQ-A3334, an oral toll-like receptor 7 agonist in healthy individuals

“…Women had higher TQ-A3334 exposure than men, indicating the possible higher response in female patients. This could be the reason for the increase in PD response, a higher decrease of lymphocyte count, and higher rates of interferon-like flu symptoms in women [23]. Recently, in male patients with severe COVID-19, X-chromosomal TLR7 deficiency was associated with impaired type I and II IFN responses [24].TLR7 is encoded by the X-chromosome.…”

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

“…While the clinical studies of the dual SGLT1/2 inhibitor licogliflozin for T2DM have been terminated, its clinical studies for the treatment of obesity and NAFLD are ongoing 162 , 163 . Additionally, several other SLC-based drugs targeting SGLT1, SGLT2, or both are in the pipeline under clinical trials for the treatment of T2DM, including LX-2761 (a dual SGLT1/2 inhibitor) 164 , SY-008 165 , 166 and SY-009 167 , 168 (SGLT1-specific inhibitors), and five SGLT2-specific inhibitors (rongliflozin 169 , 170 , 171 , tianagliflozin 172 , LH-1801 173 , DWC202213 174 , DA-2811 175 ). However, sergliflozin, developed by GlaxoSmithKline, was discontinued after Phase II trials (NCT00291356) 176 .…”