mizagliflozin (VGX-3235) / Kissei, GSK, Vogenx - LARVOL DELTA

Efficacy and Safety of the SGLT1 Inhibitor Mizagliflozin in Patients with Post-Bariatric Hypoglycemia (ENDO 2025) - P2 | "Miza was well-tolerated with no withdrawals and mild/moderate severity of adverse events. In conclusion, treatment with Mizagliflozin led to clinically meaningful improvements in postprandial glucose and insulin, and reductions in Level 3 and Level 2 hypoglycemic events."

Clinical • Gastrointestinal Disorder • Hypoglycemia

Dysfunctional glucose metabolism triggers oxidative stress to induce kidney injury in diabetes. (PubMed, World J Diabetes) - "Oxidative stress stimulates proinflammatory factor production and kidney inflammatory injury. Mizagliflozin decreases glucose reabsorption and thus ameliorates diabetes-induced kidney injury."

Journal • Diabetes • Inflammation • Metabolic Disorders • Renal Disease

Mizagliflozin ameliorates diabetes induced kidney injury by inhibitor inhibit inflammation and oxidative stress. (PubMed, World J Diabetes) - "These findings indicate that MIZ can ameliorate DN by inhibiting SGLT1, inflammation, and oxidative stress."

Journal • Diabetes • Diabetic Nephropathy • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • CAT

Sodium-dependent glucose co-transport proteins (SGLTs) are not involved in human glucose taste detection. (PubMed, PLoS One) - "Phlorizin (0.2 mM) and the high potency SGLT1-selective inhibitor mizagliflozin (10 μM) failed to inhibit glucose taste detection measured at peri-threshold concentrations in the rapid throughput taste discrimination assay...Taken together the results indicate that agonist activation of TAS1R2/R3 is sufficient to account for all glucose taste without contribution by an alternative SGLT-mediated signaling pathway. Furthermore, the taste of phlorizin could be a confounding variable for studies evaluating a role for SGLTs in taste."

Journal

Effect of Mizagliflozin Repeat Dosing on Adverse Events and Postprandial Glucose Excursions (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Vogenx, Inc. | Trial completion date: Aug 2024 ➔ May 2025

Trial completion date • Hypoglycemia

Crucial role for sensory nerves and Na/H exchanger inhibition in dapagliflozin and empagliflozin-induced arterial relaxation. (PubMed, Cardiovasc Res) - "SGLT2 inhibitors relax mesenteric arteries by promoting the release of CGRP from sensory nerves in a NHE1-dependent manner."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Effect of Mizagliflozin Repeat Dosing on Adverse Events and Postprandial Glucose Excursions (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Vogenx, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Aug 2024 | Trial primary completion date: Dec 2023 ➔ May 2024

Adverse events • Enrollment closed • Trial completion date • Trial primary completion date • Hypoglycemia

SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast. (PubMed, Breast Cancer Res Treat) - "High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • KDR

Effect of Mizagliflozin Repeat Dosing on Adverse Events and Postprandial Glucose Excursions (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Vogenx, Inc. | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Hypoglycemia

Inhibition Of Intestinal SGLT1 With Mizagliflozin For The Treatment Of Post-bariatric Hypoglycemia (ENDO 2023) - P2 | "These data are consistent with previous studies showing excellent safety and tolerability. Improvements in glucose nadir and reductions in both peak glucose and insulin were observed, supportive of further development of Miza as an orally administered treatment for PBH."

Late-breaking abstract • Gastrointestinal Disorder • Hypoglycemia • Pain

Effect of Mizagliflozin Repeat Dosing on Adverse Events and Postprandial Glucose Excursions (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Vogenx, Inc. | Trial completion date: Sep 2023 ➔ Dec 2023 | Initiation date: Mar 2023 ➔ Jun 2023 | Trial primary completion date: Sep 2023 ➔ Dec 2023

Adverse events • Trial completion date • Trial initiation date • Trial primary completion date • Hypoglycemia

Effect of Mizagliflozin on Postprandial Glucose and Insulin in Post-Bariatric Hypoglycemia Subjects (clinicaltrials.gov) - P2 | N=10 | Completed | Sponsor: Vogenx, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hypoglycemia

Effect of Mizagliflozin on Postprandial Glucose and Insulin in Post-Bariatric Hypoglycemia Subjects (clinicaltrials.gov) - P2 | N=9 | Active, not recruiting | Sponsor: Vogenx, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hypoglycemia

Effect of Mizagliflozin Repeat Dosing on Adverse Events and Postprandial Glucose Excursions (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Vogenx, Inc.

Adverse events • New P2 trial • Hypoglycemia

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption During Peritoneal Dialysis in Rats (KIDNEY WEEK 2022) - "Methods Here we tested a selective blocker of sodium glucose co-transporter 1, mizagliflozin, as well as phloretin, a non-selective blocker of facilitative glucose channels in an experimental model of peritoneal dialysis in anesthetized Sprague-Dawley rats...95% confidence intervals of phloretin effect on Isocratic, Isovolumetric and Three-pore model glucose diffusion capacity (MTAC), Three-pore model urea MTAC, ultrafiltration-rate (UF-rate) and sodium removal compared to sham group. Interval marker represent the median of the difference."

Preclinical • Anesthesia

Effect of Mizagliflozin on Postprandial Glucose and Insulin in Post-Bariatric Hypoglycemia Subjects (clinicaltrials.gov) - P2 | N=9 | Recruiting | Sponsor: Vogenx, Inc.

New P2 trial • Hypoglycemia