Mizagliflozin (MIZ) is a specific inhibitor of sodium-glucose cotransport protein 1 (SGLT1) originally developed as a medication for diabetes.

To explore the impact of MIZ on diabetic nephropathy (DN).

Diabetic mice were created using db/db mice. They were administered either a low dose (0.5 mg/kg) or a high dose (1.0 mg/kg) of the SGLT1 inhibitor MIZ via stomach gavage for 8 weeks. Subsequently, mesangial cells (MCs) were isolated and subjected to high glucose conditions in culture to assess the effects of MIZ on DN.

The results showed that low doses of MIZ significantly reduced albuminuria to a level comparable to that achieved with high doses in db/db mice. High doses of MIZ led to a substantial increase in body weight in mice, along with decreased blood glucose levels and food intake. Moreover, the intervention with high-dose MIZ notably decreased the expression of extracellular matrix genes, such as collagen type 1 alpha 1 mRNA levels. While the expression of SGLT1 increased after exposure to high glucose, it decreased following treatment with MIZ. Furthermore, MIZ intervention was more effective in improving lactate dehydrogenase levels in MCs induced by high glucose compared to canagliflozin. MIZ also significantly elevated levels of antioxidant enzymes superoxide dismutase, catalase, and glutathione, while reducing malondialdehyde levels.

These findings indicate that MIZ can ameliorate DN by inhibiting SGLT1, inflammation, and oxidative stress.

Irritable bowel syndrome (IBS) is a common, symptom-based disorder of chronic abdominal pain and altered bowel habits. The pathogenesis of IBS is multifactorial, leading to the potential for the development of multiple, diverse treatment strategies. This mechanistic heterogeneity also leads to the realization that available therapies are only effective in a subset of IBS suffers. Current US Food and Drug Administration (FDA) approved therapies for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) are reviewed. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction with currently available IBS treatments. Only a small percentage of IBS patients are on prescription therapies underscoring the potential market and need for additional therapeutic options.

: Expanding on currently available therapies, the serotonergic and endogenous opioid receptor systems continue to be a focus of future IBS treatment development. Additional novel emerging therapies include the endogenous cannabinoid system, bile acid secretion and sequestration, and exploit our enhanced understanding of visceral sensory signaling and intestinal secretomotor function.

While challenges remain for the future development of IBS therapies, the diverse etiologies underlying the disorder present an opportunity for novel therapies. Hence, great potential is anticipated for future IBS treatment options.