Voglibose

Developing effective α-glucosidase inhibitors is critical for managing hyperglycemia in individuals with high-carbohydrate diets; however, current drugs exhibit limitations in both efficacy and tolerability. In the present study, 25 derivatives of neoponkoranol, an active sulfonium type α-glucosidase inhibitor identified from Genus Salacia were synthesized. These compounds containing a methyl-glycosyl furanose scaffold modified with various hydrophobic groups at the 5'-O-position, were characterized using HRMS and NMR spectroscopy. Biological evaluations demonstrated a selectively enhanced maltase inhibition profile while maintaining broad-spectrum activity. Most sulfonium salts exhibited potent inhibitory activity against maltase and sucrase with IC₅₀ values ranging from 0.14 to 2.21 μM; these potencies are comparable to or superior to those of the positive controls acarbose and voglibose. In addition, the designed derivatives also exhibited strong isomaltase inhibitory activities whereas acarbose was almost inactive against this enzyme. Compound LY-23 emerged as the most potent inhibitor with maltase IC₅₀ = 0.18 ± 0.03 μM, sucrase IC₅₀ = 0.14 ± 0.01 μM, and isomaltase IC₅₀ = 0.51 ± 0.06 μM. Mechanism studies characterized LY-23 as a competitive inhibitor. Molecular docking along with 3D fluorescence and CD spectral analyses indicated that LY-23 binds to α-glucosidase, inducing secondary structural and conformational changes in the enzyme. Furthermore, LY-23 showed no significant cytotoxicity in HEK293T and L02 cells. Remarkably, in vivo studies revealed that the oral administration of LY-23 (1.0 or 10.0 mg/kg) effectively reduced postprandial blood glucose levels in normal ICR mice following maltose or sucrose loading, with an efficacy comparable to that of voglibose (1.0 mg/kg) and acarbose (20.0 mg/kg), respectively. These findings highlight LY-23 as a promising candidate for the development of novel α-glucosidase inhibitors with antihyperglycemic properties.

Type 2 diabetes mellitus (T2DM) poses a significant global health challenge, impacting millions of people worldwide. While many studies focus on HbA1c levels, there remains a need to evaluate glycemic variability and postprandial glucose (PPG) excursions. Therefore, this study was conducted to assess and compare the safety and effectiveness of nutritional therapy and alpha-glucosidase inhibitors in achieving rapid PPG stabilization in an Indian subpopulation of patients with T2DM.

This short-term open-label study included T2DM patients uncontrolled on metformin and sulfonylurea. The study enrolled 60 participants (40 males, 20 females) with a mean age of 54.06 ± 6.04 years, with the majority being 30-60 years of age (85%). All patients were given intermittent medical nutritional therapy (low glycemic index (LGI) diet) and alpha-glucosidase inhibitors (AGIs; acarbose, voglibose) to manage postprandial glycemia. A rotational design ensured that each group experienced all interventions in varying sequences for a comprehensive analysis of their effects. Glycemic responses were assessed using finger-stick capillary glucose measurements and continuous glucose monitoring (CGM) to evaluate postprandial and 24-hour glycemic variability.

Postprandial mean glucose levels were significantly reduced with all interventions (p<0.05), with the highest reduction observed with acarbose. Between AGIs, the adverse effects were similar between medications. The 24-hour mean glucose levels, mean amplitude of glycemic excursion, and area under the curve for 24-hour glycemic fluctuations were significantly lower with interventions, especially acarbose.

We conclude that AGIs and LGI diets effectively reduce postprandial glucose, especially in Indian T2DM patients consuming high-carbohydrate diets with a high glycemic load.