Miglitol targets α-glucosidase enzymes (glucoamylase, sucrase and isomaltase) in the brush border membrane of the small intestine. No IC50, Ki, EC50 or DC50 values are reported in this paper.[1]
Miglitol targets alpha-glucosidase enzymes in the small intestine. It inhibits these enzymes, which are responsible for breaking down complex carbohydrates into absorbable monosaccharides. By inhibiting alpha-glucosidase, miglitol delays the digestion and absorption of carbohydrates, reducing postprandial hyperglycemia. Miglitol has IC50 values of 0.35, 0.11, 1.3, and 1.2 µM for human lysosomal alpha-glucosidase and rat sucrase, maltase, and isomaltase, respectively. It is selective for human alpha-glucosidase over beta-glucosidase (IC50 = 84 µM). Unlike other drugs of the same class, miglitol is not metabolized and is excreted unmetabolized by the kidneys.

Miglitol is an oral anti-diabetic drug that acts by inhibiting the ability of the patient to breakdown complex carbohydrates into glucose.
Kinase Assay: Miglitol is an oral anti-diabetic drug that acts by inhibiting the ability of the patient to breakdown complex carbohydrates into glucose. It is primarily used in diabetes mellitus type 2 for establishing greater glycemic control by preventing the digestion of carbohydrates (such as disaccharides, oligosaccharides, and polysaccharides) into monosaccharides which can be absorbed by the body.

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Cell Assay: Miglitol inhibits glycoside hydrolase enzymes called alpha-glucosidases. Since miglitol works by preventing digestion of carbohydrates, it lowers the degree of postprandial hyperglycemia. It must be taken at the start of main meals to have maximal effect. Its effect will depend on the amount of non-monosaccharide carbohydrates in a persons diet. Dietary supplementation with miglitol from pre-onset stage in OLETF rats delays the onset and development of diabetes and preserves the insulin secretory function of pancreatic islets.
In vitro studies have demonstrated that Miglitol is a potent inhibitor of alpha-glucosidase. It has IC50 values of 0.35 µM for human lysosomal alpha-glucosidase and 0.11, 1.3, and 1.2 µM for rat sucrase, maltase, and isomaltase, respectively. Miglitol is selective for human alpha-glucosidase over beta-glucosidase (IC50 = 84 µM). These in vitro findings confirm the compound's mechanism of action as an alpha-glucosidase inhibitor. The compound's potency and selectivity make it an effective antidiabetic agent. In vitro studies may also assess the compound's effects on other enzymes and its potential for drug interactions.

Miglitol was orally administered at 40 mg/100 g of high-fat diet containing 45% kcal as fat to 12-week-old rats for 29 days, and age-matched rats without the agent were used as the respective controls
In vivo: Miglitol dietary supplementation (800 ppm) for 65 weeks in OLETF rats significantly reduced non-fasting blood glucose concentrations at week 64 compared to control OLETF rats (185±14 vs 455±125 mg/100 ml, P<0.05). Oral glucose tolerance test at week 63 showed that Miglitol-treated OLETF rats had markedly lower blood glucose levels at 1, 2 and 3 h after glucose loading, with a peak at 0.5 h (448 mg/100 ml) and return to fasting level by 3 h, whereas control OLETF rats had a peak at 1 h (591 mg/100 ml) and remained elevated at 3 h (438 mg/100 ml). The incremental AUC₀₋₃ₕ for blood glucose was significantly lower in Miglitol-treated OLETF rats (599±69 mg/100 ml·h) than in control OLETF rats (873±92 mg/100 ml·h). Plasma insulin concentrations after glucose loading were significantly higher in Miglitol-treated OLETF rats at 0.25–2 h compared to control OLETF rats, and the ΔAUC₀₋₃ₕ for plasma insulin was significantly higher (14.59±1.98 vs 3.53±2.20 ng/ml·h). Miglitol treatment significantly reduced HbA1c levels (3.9±0.2% vs 7.7±1.8% in control) and tended to reduce serum triglycerides and free fatty acids at week 65. Urinary C‑peptide excretion at weeks 52 and 60 was lower in Miglitol-treated OLETF rats than in controls. Histological analysis at week 65 showed that Miglitol treatment significantly increased the number of islets (shortest diameter >150 μm: 15.4±1.6 per 10 sections vs 7.3±2.2 in control), reduced fibrosis area per islet (27±2% vs 43±3%), and increased β‑cell area per islet (41±2.8% vs 25±7.4%). Miglitol preserved islet structure and prevented loss of β‑cells.[1]
In vivo studies have demonstrated that Miglitol suppresses postprandial hyperglycemia and reduces plasma glucose concentration in normal rats and in several animal models of diabetes. The compound's efficacy in improving glycemic control has been confirmed in clinical trials in patients with type 2 diabetes. Miglitol is used as monotherapy or in combination with other antidiabetic agents to achieve glycemic targets. Its mechanism of action, which does not involve insulin secretion, makes it a valuable option for patients who cannot tolerate or are not candidates for other antidiabetic therapies. The compound's lack of metabolism and renal excretion contribute to its favorable pharmacokinetic profile.

Non-cellular enzyme assays for Miglitol typically involve measuring the activity of alpha-glucosidase enzymes in the presence of the compound. These assays use purified enzymes or intestinal tissue homogenates and a chromogenic or fluorogenic substrate (e.g., p-nitrophenyl-alpha-D-glucopyranoside) to measure enzyme activity. Miglitol is tested at various concentrations to determine its IC50 for alpha-glucosidase inhibition. Dose-response curves are generated, and IC50 values are calculated using non-linear regression analysis. These assays may also be performed with different alpha-glucosidase isoforms (e.g., sucrase, maltase, isomaltase) to assess the selectivity of Miglitol. The specificity for alpha-glucosidase over beta-glucosidase can also be evaluated.

In vitro cell-based assays for Miglitol are not typically performed, as the compound's activity is assessed in enzyme assays and in vivo models rather than in mammalian cell-based assays. However, cytotoxicity assays may be performed in mammalian cell lines to assess the compound's safety profile. These assays typically involve culturing cells in appropriate media and treating them with Miglitol at various concentrations. Cell viability is assessed using MTT or similar assays. The compound's selectivity for alpha-glucosidase over other enzymes and its low toxicity to mammalian cells contribute to its favorable safety profile. Miglitol is typically dissolved in water or DMSO for in vitro studies.

40 mg/100 g; oral rats

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Animal Protocol: Male OLETF rats (5 weeks old) were fed a control diet (based on AIN formulation containing 20% casein, 40.5% corn starch, 16% sucrose, 8% corn oil, 5.4% lard) or the same diet supplemented with 800 ppm (0.8 g/kg diet) Miglitol for 65 weeks. Non-diabetic male LETO rats were fed the control diet. Rats were housed individually with free access to food and tap water under controlled conditions (22±2°C, 55±5% humidity, 12‑h light/dark cycle). Non-fasting blood samples were collected from the tail vein using heparin-lithium capillary tubes at weeks 16, 28, 40, 44, 52, and 64 between 09:30–10:30. At week 63, an oral glucose tolerance test (OGTT) was performed after overnight fasting (20:00–10:00). Rats received a single dose of 40% glucose solution at 5 ml/kg (2 g/kg body weight) by gastric tube. Blood samples were collected from the tail vein at 0.25, 0.5, 1, 2, and 3 h after glucose loading. At week 65, rats were sacrificed and serum was collected from the inferior vena cava. Urine was collected for 24 h at weeks 20, 27, 44, 52, and 60 to measure C‑peptide. The whole pancreas was removed, fixed, and paraffin sections (4 μm thick) were prepared for histology and immunostaining.[1]
In vivo animal studies for Miglitol typically involve rodent models of diabetes, such as streptozotocin-induced diabetic rats or genetically diabetic mice. Animals are administered Miglitol orally at various doses, and blood glucose levels are measured at multiple time points post-administration, particularly after a carbohydrate load (e.g., sucrose or starch). The compound's ability to suppress postprandial hyperglycemia is assessed by comparing blood glucose excursions in treated versus control animals. Dose-response studies are conducted to determine the minimum effective dose and the maximal efficacy. Body weight, food intake, and gastrointestinal tolerance are monitored throughout the study. These studies are essential for establishing the efficacy and safety of Miglitol in preclinical settings.

Absorption, Distribution and Excretion
Miglitol absorption is saturated at high doses; a 25 mg dose is completely absorbed, while a 100 mg dose is only 50-70% absorbed. There is no evidence that systemic absorption of miglitol enhances its therapeutic effect. Miglitol is not metabolized in humans or any of the animal species studied. It is excreted unchanged via the kidneys. 0.18 L/kg Miglitol absorption is saturated at high doses: a 25 mg dose is completely absorbed, while a 100 mg dose is only 50%-70% absorbed. Peak plasma concentrations are reached within 2-3 hours at all doses. The therapeutic effect is primarily due to its local action on the small intestine; there is no evidence that systemic absorption contributes to the therapeutic response. The protein binding rate of miglitol is negligible (<4.0%). The volume of distribution of miglitol is 0.18 L/kg, consistent with its predominant distribution in the extracellular fluid. Miglitol is primarily distributed in the extracellular fluid and concentrates in the intestinal cells of the small intestine. For more complete data on the absorption, distribution, and excretion of miglitol (9 items in total), please visit the HSDB record page. Metabolism/Metabolites Miglitol is not metabolized in humans or any of the animal species studied. No metabolites have been detected in plasma, urine, or feces, indicating no systemic or first-pass metabolism. Biological Half-Life The elimination half-life of miglitol from plasma is approximately 2 hours. ... Miglitol is rapidly eliminated from plasma, with an apparent elimination half-life of 0.4–1.8 hours. ... At very low concentration levels, the terminal elimination phase of radioactive substances is characterized by a half-life of 50–110 hours... The elimination half-life of miglitol from plasma is approximately 2 hours.

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Pharmacokinetic studies of Miglitol have shown that it is absorbed from the gastrointestinal tract, though its systemic bioavailability is low due to its action in the intestinal lumen. Unlike other drugs of the same class, miglitol is not metabolized and is excreted unmetabolized by the kidneys. The compound's half-life and other PK parameters are available in the clinical pharmacology literature. Miglitol is approved for clinical use and is available by prescription for the treatment of type 2 diabetes. Its favorable pharmacokinetic profile, including the lack of metabolism, contributes to its low potential for drug interactions. Miglitol is typically administered orally three times a day with meals.

Hepatotoxicity
In several large clinical trials, the incidence of elevated serum transaminases in the miglitol group was not higher than in the placebo group, and all elevations were asymptomatic, returning to normal rapidly after discontinuation of the drug. Neither during these studies nor since miglitol's approval and widespread clinical use have there been reports of clinically significant liver injury caused by miglitol. Therefore, even if miglitol-induced liver injury occurs, it must be extremely rare. Furthermore, there are no reports of patients switching to miglitol after experiencing liver injury while taking acarbose. Probability Score: E (Unlikely to cause clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Limited data suggest that miglitol is rarely excreted into breast milk. Due to the low oral absorption rate of miglitol, it is unlikely to have adverse effects on breastfed infants. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
The protein binding rate of miglitol is negligible (<4.0%).

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Interactions
Several studies have explored the potential interaction between miglitol and glibenclamide. In a study of six healthy volunteers, subjects received a single 5 mg dose of glibenclamide in addition to a six-day course of miglitol (50 mg three times daily for four days; followed by 100 mg three times daily for two days) or placebo. Results showed that the mean Cmax and AUC values of glibenclamide were reduced by 17% and 25%, respectively, compared to miglitol alone. Another study in diabetic patients explored the effects of adding miglitol (100 mg three times daily for seven days) or placebo to a daily course of 3.5 mg glibenclamide. The results showed that the mean AUC value decreased by 18% in the miglitol treatment group, but this difference was not statistically significant. More information on potential interactions with glibenclamide comes from a large US clinical trial (Study 7). In this trial, patients received either miglitol or a placebo in addition to taking 10 mg glibenclamide twice daily. At 6 months and 1 year follow-up, patients taking 100 mg miglitol three times daily had a 16% and 8% lower mean Cmax value for glibenclamide, respectively, compared to patients taking glibenclamide alone. However, these differences were not statistically significant. Therefore, although there is a trend towards lower AUC and Cmax values for glibenclamide when used in combination with miglitol, based on the above three studies, no definitive conclusions can be drawn regarding potential interactions. The pharmacokinetics of miglitol on a single dose of 1000 mg metformin were investigated in healthy volunteers. Compared to the placebo group, volunteers taking miglitol experienced a 12% to 13% reduction in mean AUC and Cmax values for metformin, but this difference was not statistically significant. In a study of healthy volunteers, concomitant administration of miglitol and digoxin three times daily reduced mean plasma concentrations of digoxin by 19% and 28%, respectively. However, in diabetic patients receiving digoxin treatment, concomitant administration of miglitol did not alter plasma digoxin concentrations… Other studies in healthy volunteers have shown that miglitol significantly reduces the bioavailability of ranitidine and propranolol by 60% and 40%, respectively. No pharmacokinetic or pharmacodynamic effects of miglitol on nifedipine were observed. For more complete data on miglitol interactions (9 in total), please visit the HSDB records page.

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Toxicological data for Miglitol have been evaluated in preclinical studies and clinical trials. The compound is generally well-tolerated at therapeutic doses, with the most common adverse effects being gastrointestinal disturbances (e.g., flatulence, diarrhea, abdominal pain) due to the increased delivery of undigested carbohydrates to the colon. These effects are dose-dependent and tend to diminish over time. Miglitol has a favorable safety profile, with no significant systemic toxicity. The compound's lack of metabolism and renal excretion contribute to its low potential for drug interactions. Miglitol is approved for clinical use and is available by prescription.

Eur J Pharmacol.2009 Dec 10;624(1-3):51-7;Horm Metab Res.2009 Mar;41(3):213-20.

Therapeutic Uses
1-Deoxynojirimycin/ analogues and derivatives; α-glucosidase/antagonists and inhibitors; enzyme inhibitors. In healthy individuals, a single dose may result in a sustained decrease in postprandial blood glucose levels for 3-4 hours. Miglitol is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. /US product label contains/

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Drug Warnings Miglitol is contraindicated in patients with known hypersensitivity to this drug or diabetic ketoacidosis. This drug is contraindicated in patients with inflammatory bowel disease, ulcerative colitis, partial intestinal obstruction or those susceptible to this disease, chronic intestinal diseases with significant digestive or malabsorption disorders, and other comorbidities that may exacerbate the condition due to increased intestinal gas production. Miglitol alone, taken on an empty stomach or after a meal, does not cause hypoglycemia. The risk of hypoglycemia increases when miglitol is used in combination with insulin or sulfonylureas. If hypoglycemia occurs, the dosage of these medications should be adjusted accordingly. For mild to moderate hypoglycemia, oral glucose (dextrose) should be used instead of sucrose (table sugar, a disaccharide); miglitol does not delay the absorption of oral glucose (a monosaccharide). Severe hypoglycemia may require intravenous glucose infusion or glucagon injection. In stressful situations (e.g., fever, trauma, infection, surgery), patients taking miglitol may be at risk of losing glycemic control; temporary insulin use may be necessary. For more drug warnings about miglitol (full version) (11 in total), please visit the HSDB record page.

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Pharmacodynamics
Miglitol is an oral alpha-glucosidase inhibitor, a derivative of deoxynojirimycin, that delays the digestion of ingested carbohydrates, thereby reducing the postprandial rise in blood glucose concentration. Due to the reduced plasma glucose levels, miglitol can lower glycated hemoglobin levels in patients with type II (non-insulin-dependent) diabetes. Systemic non-enzymatic protein glycosylation, reflected in glycated hemoglobin levels, is a function of mean blood glucose concentration over time. Due to their different mechanisms of action, miglitol's effect in enhancing glycemic control has an additive effect when used in combination with sulfonylureas. Furthermore, miglitol can reduce the insulin-stimulating and weight-gaining effects of sulfonylureas. Miglitol has a weak inhibitory effect on lactase; therefore, at recommended doses, it is not expected to cause lactose intolerance.

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Additional Info: Miglitol is an α-glucosidase inhibitor that suppresses postprandial hyperglycemia by delaying carbohydrate absorption, thereby reducing post-meal insulin secretion and protecting pancreatic β‑cells from the deleterious effects of chronic hyperglycemia and excessive insulin secretion. This study shows that early and long-term dietary supplementation with Miglitol delays the onset and progression of type 2 diabetes in OLETF rats (a model of obesity‑related diabetes), preserves insulin secretory capacity, reduces islet fibrosis, and maintains β‑cell mass. No digestive symptoms (e.g., diarrhea) were observed throughout the 65‑week treatment at 800 ppm. The findings suggest that Miglitol may be beneficial in preventing diabetes caused by overeating.[1]
Miglitol (BAY1099; Glyset) is an oral alpha-glucosidase inhibitor used for the management of type 2 diabetes mellitus. It has the CAS number 72432-03-2. Miglitol delays the digestion of carbohydrates, reducing postprandial hyperglycemia. It has IC50 values of 0.35, 0.11, 1.3, and 1.2 µM for human lysosomal alpha-glucosidase and rat sucrase, maltase, and isomaltase, respectively. Unlike other drugs of its class, miglitol is not metabolized and is excreted unmetabolized by the kidneys. Miglitol is approved for clinical use and is available by prescription.

C8H17NO5

207.22

207.11

72432-03-2

Miglitol-d4;2714473-10-4

441314

White to pale-yellow powder
Crystals from ethanol

1.5±0.1 g/cm3

453.7±45.0 °C at 760 mmHg

114ºC

284.3±27.4 °C

0.0±2.5 mmHg at 25°C

1.598

-1.4

5

6

3

14

179

4

O([H])[C@@]1([H])[C@@]([H])([C@]([H])(C([H])([H])N(C([H])([H])C([H])([H])O[H])[C@]1([H])C([H])([H])O[H])O[H])O[H]

IBAQFPQHRJAVAV-ULAWRXDQSA-N

InChI=1S/C8H17NO5/c10-2-1-9-3-6(12)8(14)7(13)5(9)4-11/h5-8,10-14H,1-4H2/t5-,6+,7-,8-/m1/s1

(2R,3R,4R,5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 100 mg/mL (482.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)