Miglitol, α-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome: A randomized comparable study

https://doi.org/10.1016/j.ijcard.2012.05.109Get rights and content

Abstract

Background/objectives

Visceral fat obesity plays an essential role in the clustering of cardiovascular risk factors. This study aimed to clarify the effects of miglitol, α-glycosidase inhibitor, on body weight, fat distribution and cardiovascular risk factors in patients with the metabolic syndrome.

Methods and results

One hundred and eleven drug naive patients with the metabolic syndrome were continuously recruited and randomly allocated to a group of life style modification (LSM) alone or a group of LSM with miglitol per os 50 mg × 3 (LSM + miglitol). After 12 weeks of treatment, body weight (5.1%), body mass index (4.9%) and waist circumference were greatly reduced in miglitol group (n = 42) than in LSM group (n = 43). Plasma levels of insulin and glucose during an oral 75 g glucose loading were decreased only in miglitol group. Visceral fat area, determined by abdominal computed tomography, was greatly reduced in miglitol group (baseline 188 vs 12 weeks 161 cm2, p < 0.0001) than in LSM group (184 vs 174 cm2, p < 0.05). Subcutaneous fat area was reduced only in miglitol group (p < 0.001). Systolic blood pressure was reduced in miglitol group (142 vs 133 mm Hg, p < 0.001), but not in control group (137 vs 134 mm Hg). Serum levels of triglyceride, LDL-cholesterol, γ-GTP, and high-sensitive CRP were decreased and adiponectin was increased only in miglitol group.

Conclusions

Our results indicated that miglitol showed an anti-obesity potential, which was achieved by reducing abdominal fat accumulation and/or enhanced insulin requirement, and then corrected both the metabolic and hemodynamic aberrations seen in patients with the metabolic syndrome (UMIN Clinical Trial Registry UMIN000007650).

Introduction

The metabolic syndrome is a cluster of common cardiovascular risk factors including hypertension, glucose intolerance, dyslipidemia and visceral fat obesity [1], [2], [3]. The notion has been proposed that visceral fat obesity is the central element in this syndrome and could be causally involved in clustering of the other components [4]. Actually, losing 5–10% of body weight was shown to reduce the traditional cardiovascular risks [5], [6]. Currently ongoing are clinical trials that use health-promoting lifestyle interventions, new drugs and even surgery, which are all aimed at weight loss, reduction in disease manifestations, and improved outcomes [5], [6].

Two placebo-controlled randomized trials using α-glycosidase inhibitors revealed that acarbose and voglibose, respectively, improved postprandial hyperglycemia and reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance (IGT) [7], [8]. Meta-analysis of seven randomized, double-blind, placebo-controlled acarbose studies [Meria7] showed that acarbose prevents myocardial infarction and cardiovascular diseases in type 2 diabetic patients [9]. Noteworthy was the fact that acarbose reduced body weight and body mass index in the diabetic patients, accompanied by improvement in glycemic, triglyceride and systolic blood pressure controls. These observations suggest that inhibition of postprandial hyperglycemia by α-glycosidase inhibitors may be a therapeutic strategy for reducing risks for diabetes, hypertension, dyslipidemia and cardiovascular diseases in patients with high-risk obesity such as the metabolic syndrome. Selective inhibition of α-glycosidase enzymes delays carbohydrate digestion in the small intestine and reduces the postprandial rise in plasma glucose. Such profiles could avoid enhanced insulin requirement/hyperinsulinemia and might be protecting from visceral fat accumulation. But, such notion of α-glycosidase inhibitors on fat remodeling has never been elucidated.

In this open-label, prospective, randomized study, patients with the metabolic syndrome were treated either by life style modification (LSM) or LSM with miglitol, and visceral fat distribution and glucose/insulin profiles were evaluated.

Section snippets

Subjects

Participants visited our hospital by self-referral or by recommendation for further check-up of life-style related disease at local center screening (Diabetes and Life-style Related Disease Center, Tomishiro Central Hospital). The studied subjects included men and women aged between 34 and 69 years with the metabolic syndrome, defined according to the 2005 IDF guideline [2]. In the IDF criteria, subjects to be defined as metabolic syndrome have abdominal obesity (modified Japanese criteria,

Baseline characteristics

A total of 111 patients were enrolled, with 56 randomized to LSM group and 55 to LSM + miglitol group, and 50 of LSM and 48 of LSM + miglitol were available for analysis (Fig. 1). Baseline characteristics did not differ between the two groups: LSM group included 39 male and 17 female with a mean age of 55 ± 12 years, and LSM + miglitol group included 38 male and 17 female with a mean age of 54 ± 10 years. At baseline before treatment, body weight, BMI, waist circumference, blood pressure and heart rate

Discussions

Our study indicated that miglitol, in contrast to LSM alone, profoundly decreases body weight, BMI and waist circumference in patients with the metabolic syndrome. In addition, data provide evidence that body weight reduction by miglitol is closely correlated with a reduction in visceral adiposity and also with improvement in indices of insulin resistance. Finally, the reduction in visceral adiposity was accompanied by overall improvement in metabolic derangements such as glucose intolerance,

Acknowledgments

This study supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare (MHLW), and the Suzuken Memorial Foundation. We deeply thank Ms. Hiroe Shinjo, Ms. Saeko Nakamura, Ms. Ayano Tajima and Ms. Rie Shiroma for dedicated secretarial assistance, Ms. Tokiko Kinjo and Ms. Kaori Ichimatsu for experienced nutritional counseling and Dr. Hideaki Tanaka, Dr. Yoshinao Uezu, and Dr. Yoshiki Shiohira for encouragement and valuable

References (25)

  • M. Hanefeld et al.

    Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta‐analysis of seven long-term studies

    Eur Heart J

    (2004)
  • T. Yoshizumi et al.

    Abdominal fat: standardized technique for measurement at CT

    Radiology

    (1999)
  • Cited by (33)

    • Bioactivity-guided isolation of a bioactive compound with α-glucosidase inhibitory activity from the leaves extract of Sauropus androgynus

      2023, Sustainable Chemistry and Pharmacy
      Citation Excerpt :

      However, the use of these medications is not without side effects. There have been reports that these drugs can cause diarrhea, flatulence, and more severe symptoms, such as severe cholestasis and metabolic hypoglycemic episodes (Shimabukuro et al., 2012). Exploration on alternative medicines with minimum side effects to treat DMT2 is still continuing, one of which is by resorting to naturally-derived medications, either in the form of plant extracts, enriched fractions, or single isolated compounds.

    • Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts

      2022, Gastroenterology
      Citation Excerpt :

      In this other cohort, we also found that homozygous carriers had markedly higher levels of circulating acetate, which was likely only detectable due to the lack of fasting in these participants. Notably, the effect of the naturally occurring specific loss of SI function seemed to be greater on weight and levels of triglycerides compared with drug-induced unspecific inhibition of α-glucosidases by acarbose, voglibose, or miglitol,32–38 and the impact of loss of SI function on triglyceride levels was equal to the reported effect of the lipid-lowering drug statins.39,40 Moreover, altered high-density lipoprotein metabolism among homozygous carriers suggested increased health-promoting removal of cholesterol from extrahepatic tissues.

    • Biomarkers in metabolic syndrome

      2022, Advances in Clinical Chemistry
      Citation Excerpt :

      VAT was significantly reduced by 7.2% (161.3 to 148.4 cm2, P < 0.05), suggesting a new therapeutic approach. In another drug intervention study, miglitol (50 mg tid) was administered for 12 weeks to 55 Japanese patients (average 54 y) with MetS (I) [20]. VAT was significantly reduced (186 to 165 cm2; P < 0.0001).

    • Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin

      2016, Peptides
      Citation Excerpt :

      Miglitol and metformin can also improve glycemic control as well as lower the incidence of hypoglycemia and obesity because these drugs do not induce insulin secretion. Indeed, a RCT reported that the prevalence of indicators of weight gain (the BMI, waist circumference, accumulation area of visceral fat) and risk factors for CVD were lower in subjects with the metabolic syndrome treated with miglitol compared with patients who undertook lifestyle modification [18]. A systematic review reported that metformin therapy with lifestyle modification reduced the BMI in T2DM patients [19].

    • Acarbose reduces body weight irrespective of glycemic control in patients with diabetes: Results of a worldwide, non-interventional, observational study data pool

      2016, Journal of Diabetes and its Complications
      Citation Excerpt :

      In addition, the body weight reduction in patients treated with aGI is reported to correlate with decreased levels of post-prandial insulin (significant) and post-prandial GIP (borderline significant) during a 2-h meal tolerance test (Narita et al., 2012). Another aGI, miglitol, in combination with lifestyle modification was shown to significantly reduce visceral fat accumulation compared with lifestyle modification alone in patients with metabolic syndrome (Shimabukuro, Higa, Yamakawa, Masuzaki, & Sata, 2013). With acarbose, it is likely that its insulin- and GIP-sparing effects, via a shift of glucose absorption site and suppression of PPG by slowing down glucose absorption, translate into the clinical benefit of body weight reduction observed in our study and the published meta-analyses (Gross et al., 2011; McIntosh et al., 2011).

    • A Case of Nonalcoholic Steatohepatitis in a Cured Acromegalic Patient With Severe Growth Hormone Deficiency

      2016, AACE Clinical Case Reports
      Citation Excerpt :

      Metformin is reported to reduce hepatocellular ballooning (13). Miglitol reduced serum levels of low-density-lipoprotein cholesterol, triglyceride linked to liver lipogenesis, and subcutaneous fat (14). In this case, her body weight and HbA1c levels increased after the operation.

    View all citing articles on Scopus
    View full text