Article They are most commonly mild-to-moderate dose-related gastrointestinal effects, such as flatulence, soft stools, diarrhea, or abdominal discomfort, and generally diminish in frequency and intensity with time. Ahr HJ, Boberg M, Brendel E, Krause HP, Steinke W. Pharmacokinetics of miglitol. and transmitted securely. If side effects occur with Miglitol tablets, they usually develop during the first few weeks of therapy. The following adverse reactions have been reported during post-approval use of Miglitol tablets. Nevertheless, miglitol is associated with minor side effects such as gastrointestinal symptoms [30]. In contrast to sulfonylureas, Miglitol tablets do not enhance insulin secretion. In one clinical trial, 200 mg 3 times daily gave additional improved glycemic control but increased the incidence of the gastrointestinal symptoms described above. There have been five basic research reports including ours [15] demonstrating that miglitol reduces obesity in rodents [1619]. JAMA. [6] demonstrated that miglitol reduced total body fat mass and lowered systolic blood pressure. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. The elimination half-life of miglitol from plasma is approximately 2 hours. January 2, 2020. Accessibility It is a white to pale-yellow powder with a molecular weight of 207.2. Taken orally, they inhibit the upper gastrointestinal enzymes (alpha-glucosidases) that convert complex polysaccharide carbohydrates into monosaccharides in a . Shimabukuro M, Higa M, Yamakawa K, Masuzaki H, Sata M. Miglitol, alpha-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome: a randomized comparable study. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Miglitol is a desoxynojirimycin derivative, and is chemically known as 3,4,5-piperidinetriol, 1- (2-hydroxyethyl) -2- (hydroxymethyl)-, [2R- (2a,3,4a, 5)]-. Unauthorized use of these marks is strictly prohibited. Follow your doctor's instructions . Gastrointestinal Disorders ileus (including paralytic ileus), subileus, gastrointestinal pain, nausea, abdominal distention. A study comparing the pharmacodynamic response to a single 50 mg dose in Black and Caucasian healthy volunteers indicated similar glucose and insulin responses in both populations. Furthermore, these previous studies involved a small number of only Japanese patients; therefore, future studies should enroll a larger number of patients, and the studies should be carried out for a longer duration in a non-blinded manner. We clarified that miglitol increased the mRNA and protein expression of UCP1 and the expression of the four proteins involved in the signaling cascade (PKA, HSL, p38MAPK, and PGC1) in high-fat diet-induced obese mice. Miglitol did not have any clastogenic effects in vivo in the mouse micronucleus test. Results from controlled, fixed-dose studies of miglitol tablets as monotherapy or as combination treatment with a sulfonylurea were combined to derive a pooled estimate of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) and postprandial plasma glucose as shown in Figures 1 and 2: Because of its mechanism of action, the primary pharmacologic effect of miglitol is manifested as a reduction in postprandial plasma glucose, as shown previously in all of the major clinical trials. External IDs . Miglitol Tablets, an oral alpha-glucosidase inhibitor for use in the management of non-insulin-dependent diabetes mellitus (NIDDM). In the peri-postnatal study in rats, the NOAEL (No Observed Adverse Effect Level) was 100 mg/kg (corresponding to approximately four times the exposure to humans, based on body surface area). eCollection 2016. Miglitol also reduced subcutaneous WAT weight in our experiment [15]. 2015;64:137685. 2012;14:2837. The recommended starting dosage of Miglitol tablets is 25 mg, given orally three times daily at the start of each main meal. Miglitol protects against age-dependent weight gain in mice: A potential role of increased UCP1 content in brown adipose tissue. Although the levels of Miglitol reached in human milk are exceedingly low, it is recommended that Miglitol tablets not be administered to a nursing woman. Nevertheless, these reports collectively suggest that miglitol activates BAT, at least in mice. Because Miglitol tablets given in combination with a sulfonylurea or insulin will cause a further lowering of blood sugar, it may increase the hypoglycemic potential of these agents. [4] enrolled the largest number of patients (n=111), which were divided into a life-style modification (LSM)-only group and an LSM-plus-miglitol treatment group. The site is secure. Skin rash was reported in 4.3% of patients treated with miglitol tablets compared to 2.4% of placebo-treated patients. Thus, although there was a trend toward lower AUC and C max values for glyburide when co-administered with Miglitol tablets, no definitive statement regarding a potential interaction can be made based on the foregoing three studies. in 1993 [16]. Patients with creatinine clearance <25 mL/min taking 25 mg 3 times daily, exhibited a greater than two-fold increase in Miglitol plasma levels as compared to subjects with creatinine clearance >60 mL/min. Miglitol is not metabolized in humans or in any animal species studied. Survival, growth, development, and fertility of the offspring were not compromised. These studies revealed no evidence of fetal malformations attributable to miglitol. Kato T, Iizuka K, Takao K, Horikawa Y, Kitamura T, Takeda J. Nutrients. There was no increased incidence of hypoglycemia in patients who took miglitol tablets in combination with sulfonylurea agents compared to the incidence of hypoglycemia in patients receiving sulfonylureas alone in any clinical trial. Following a 25 mg dose, over 95% of the dose is recovered in the urine within 24 hours. Severe hypoglycemia may require the use of either intravenous glucose infusion or glucagon injection. Yanovski SZ, Yanovski JA. The number of obese patients has increased annually worldwide. GIP promotes fat accumulation [11], whereas GLP1 reduces appetite and food intake [1214]. AR: beta adrenergic signaling; AC: adenylyl cyclase; cAMP: cyclic adenosine 3,5-monophosphate; PKA: protein kinase A; p38MAPK: p38 -mitogen-activated protein kinase; PGC1: peroxisome proliferator-activated receptor gamma coactivator 1; PPAR: peroxisome proliferator-activated receptor; RXR: retinoid X receptor; PPRE: PPAR response element; CREB: cAMP response element binding protein; CRE: cAMP response element; HSL: hormone-sensitive lipase; UCP1: uncoupling protein 1; LPL: lipoprotein lipase; TG: triglyceride; FFA: free fatty acids. Epub 2012 Nov 26. We comply with the HONcode standard for trustworthy health information. Therefore, we believe that miglitol would be easier to use than orlistat for the general population. The first study on the effects of miglitol in an animal model was reported by Debouno et al. J-STAGE, Japan Science and Technology Information Aggregator, Electronic. A role for glucagon-like peptide-1 in the central regulation of feeding. 2014;5:20612. Based on these results, the authors speculated that enhancement of BA by miglitol would increase the DIO2 expression of BAT, contributing to an increase in UCP1 expression. Membrane-bound intestinal -glucosidases hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. Miglitol tablets were statistically significantly different from placebo at all doses in each of the individual studies with respect to effect on mean one-hour postprandial plasma glucose, and there is a dose response from 25 to 100 mg 3 times daily for this efficacy parameter. An official website of the United States government. 2006;439:4849. Epub 2019 Jan 7. BA was reported to stimulate the G protein-coupled receptor of BAT (TGR5) and increase energy expenditure by activating type 2 iodothyronine deiodinase (DIO2) [29], a cyclic AMP-dependent thyroid hormone-activating enzyme. In U.S. placebo-controlled trials, the incidences of abdominal pain, diarrhea, and flatulence were 11.7%, 28.7%, and 41.5% respectively in 962 patients treated with Miglitol tablets, 25 mg to 100 mg 3 times daily, whereas the corresponding incidences were 4.7%, 10.0%, and 12.0% in 603 placebo-treated patients. Miglitol tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The maximum recommended dosage of Miglitol tablets is 100 mg 3 times daily. Maintenance or discontinuation of Miglitol tablets or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations. There were no heritable mutations detected in dominant lethal assay. Lipids. Taken orally, they inhibit the upper gastrointestinal enzymes (alpha-glucosidases) that convert complex polysaccharide carbohydrates into monosaccharides in a . The other four studies also demonstrated that miglitol reduced body weight gain with no difference of food intake in obese rodent models [15, 1719]. Miglitol tablets were evaluated in two U.S. and three non-U.S. controlled, fixed-dose, monotherapy studies, in which 735 patients treated with Miglitol tablets were evaluated for efficacy analyses (see Table 1 ). Uses for Miglitol Type 2 Diabetes Mellitus Used as monotherapy as an adjunct to diet and exercise for management of type 2 diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet and exercise alone. Miglitol. At the end of this study, the mean treatment effects on HbA1c of Miglitol tablets when added to maximum glyburide therapy were -0.30%, -0.62%, and -0.73% with the 25, 50 and 100 mg 3 times daily dosages of Miglitol tablets, respectively. However, some patients may benefit by starting at 25 mg once daily to minimize gastrointestinal adverse effects, and gradually increasing the frequency of administration to 3 times daily. 2013;62:73442. statement and The antihyperglycemic action of Miglitol results from a reversible inhibition of membrane-bound intestinal -glucoside hydrolase enzymes. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial. In addition, miglitol tablets diminish the insulinotropic and weight-increasing effects of sulfonylureas. Studies 4 and 5 were 6-month studies evaluating Miglitol tablets at 50 and 100 mg 3 times daily, and 100 mg 3 times daily, respectively. 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