Use Of Alpha-glucosidase Inhibitors Research Articles

Associations Between Thiazolidinediones Use and Incidence of Rheumatoid Arthritis: A Retrospective Population-Based Cohort Study.

Preclinical studies suggest that thiazolidinediones (TZDs) may have a protective effect on rheumatoid arthritis (RA), but evidence from population-based studies is scarce. This study aimed to assess the association between use of TZDs and incidence of RA in a retrospective cohort of patients with type 2 diabetes mellitus (T2DM). A retrospective cohort of patients with T2DM who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled. We applied the inverse probability of treatment weighted Cox model to estimate the hazard ratio (HR) of RA incidence associated with the use of TZDs compared with AGIs. The final analysis included 56,796 new users of AGIs and 14,892 new users of TZDs. The incidence of RA was 187.4 and 135.2 per 100,000 person-years in AGI users and TZD users, respectively. Compared with use of AGIs, TZD use was associated with a reduction in RA incidence, with an HR of 0.72 (95% confidence interval [95% CI] 0.59-0.89). HRs for cumulative use of TZDs for 0.51 to 4.0 years and more than 4 years with incidence of RA were 0.55 (95% CI 0.35-0.88) and 0.74 (95% CI 0.57-0.98), respectively. Various subgroup analyses and sensitivity analyses were consistent with the primary analysis. Use of TZDs is associated with a decreased risk of incident RA in patients with T2DM.

Association between α-glucosidase inhibitor use and psoriatic disease risk in patients with type 2 diabetes mellitus: A population-based cohort study.

To investigate the association between the use of alpha-glucosidase inhibitors (AGIs) and the risk of psoriatic disease (ie, psoriasis and psoriatic arthritis) in patients with type 2 diabetes mellitus (T2DM) treated with metformin. Using the 1999-2013 Taiwanese Longitudinal Cohort of Diabetes Patients Database, we identified patients with T2DM who initiated hypoglycaemic treatment between 2003 and 2012. After excluding patients with a history of psoriatic disease (International Classification of Disease, Ninth Revision, Clinical Modification codes 696.0-1) before T2DM diagnosis, patients who received antidiabetic treatment for <90days, and patients aged <20 or >100years, we identified 1390 patients who received metformin+AGIs (AGI exposure group) and 47514 patients who received metformin only (comparison group). We matched the two groups at a 1:10 ratio by age, sex, and index date of T2DM drug use. The association between AGI use and psoriatic disease risk was analysed using a Cox proportional hazard mode; time-dependent covariates for factors were reported in terms of hazard ratios (HRs) with 95% confidence intervals (CIs) after age, sex, T2DM duration, and comorbidities were controlled for. After adjusting the AGI exposure and comparison groups for potential confounders, we found that psoriatic disease risk was associated with metformin+AGI use when AGI was discontinued for 30days (HR, 8.77; 95% CI, 1.58-48.5) and when a high AGI dose was administered; furthermore, the risk declined during AGI discontinuation. This population-based study reports that AGI use and interruption of AGI use may be associated with increased psoriatic disease risk in treated patients with T2DM.

The prescription pattern of initial treatment for type 2 diabetes in Beijing from 2011 to 2015.

The purpose of this study was to describe the prescription pattern of initial treatment for type 2 diabetes (T2DM) in Beijing from 2011 to 2015.We selected 790,339 newly diagnosed outpatients with T2DM from the Beijing Medical Claim Data for Employees database between January 2011 and December 2015. The percentages of different treatments and agents were calculated from the patients' 1st prescriptions. Subgroup analyses were conducted for primary, secondary, and tertiary hospital settings.The initial treatments given to 57.7%, 30.7%, and 11.7% of patients were oral hypoglycemic agent (OHA) monotherapy, OHA polytherapy, and insulin, respectively. Alpha-glucosidase inhibitors (AGIs) (43.0%) were the most commonly used agents for monotherapy, followed by metformin (35.5%) and sulfonylureas (14.9%). AGIs were most commonly used in primary hospitals (52.0%), while metformin was prescribed most often in secondary (37.6%) and tertiary (41.8%) hospitals. From 2011 to 2015, there were increases in the use of AGIs (40.1-41.1%, P < .001) and metformin (34.0-40.4%, P < .001), but a decrease in the use of sulfonylureas (18.1-12.8%, P < .001). Similar trends were seen in the different hospital settings. Metformin plus an AGI, a sulfonylurea plus an AGI, and metformin plus a sulfonylurea were the most common OHA polytherapy combinations. The use of metformin plus an AGI increased from 13.8% in 2011 to 19.7% in 2015 (P < .001), while the use of a sulfonylurea plus an AGI, and metformin plus a sulfonylurea, did not change significantly.Half of newly diagnosed patients with T2DM received an initial treatment of OHA monotherapy. Although the use of metformin increased from 2011 to 2015, both AGIs and metformin were the most commonly prescribed agents. The patterns differed from those of most other countries and identification of the underlying reasons will require further investigation.

Alpha-glucosidase inhibitors and risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis.

Several studies have shown that anti-diabetic medications may modify the risk of cancer. We performed a systematic review and meta-analysis to evaluate the effect of alpha-glucosidase inhibitors (AGIs) on the risk of cancer in patients with diabetes mellitus. We conducted a systematic search of Medline, EMBASE, and Web of Science databases, up to September 30, 2016. Random-effects model was used to estimate the summary odds ratios (ORs) with 95% CI. Twenty-five studies (14 cohort, 7 case-control, and 4 randomized controlled trials) involving 1,285,433 patients with diabetes were included. Meta-analysis of observational studies showed that the use of AGIs was associated with a lower risk of developing cancer (OR = 0.86, 95% CI 0.78-0.96), especially gastrointestinal cancer (OR = 0.83, 95% CI 0.71-0.97). There was considerable heterogeneity across the studies introduced partly by the quality of included studies and adjustment for potential confounders. Meta-analysis of randomized controlled trials did not reveal any significant association between AGIs and cancer risk. Meta-analysis of observational studies indicated that AGIs may decrease the risk of cancer in individuals with diabetes.

Kidney Cancer and Diabetes Mellitus: A Population-Based Case-Control Study in Taiwan

The purpose of this study was to explore whether diabetes mellitus (DM) correlates with the risk of kidney cancer in Taiwan. We designed a population-based case-control study from the Taiwan National Health Insurance Database, which consisted of 116 patients with newly diagnosed kidney cancer as cases and 464 subjects without kidney cancer as controls in 2000 to 2009. Both cases and controls were aged ≥20 years. Baseline comorbidities were compared between kidney cancer cases and controls. Multivariable analysis showed no association was detected between DM and kidney cancer (OR 1.06, 95% CI, 0.58 to 1.94). Hypertension (OR 2.05, 95% CI, 1.23 to 3.42), chronic kidney diseases (OR 2.57, 95% CI, 1.23 to 5.37), cystic kidney diseases (OR 18.6, 95% CI, 1.84 to 187.6) and kidney stones (OR 4.02, 95% CI, 2.43 to 6.66) were significant comorbidities associated with increased risk of kidney cancer. Use of alpha-glucosidase inhibitor was associated with increased risk of kidney cancer (OR 4.31, 95% CI, 1.07 to 17.3). DM does not correlate with the risk of kidney cancer. Hypertension, chronic kidney diseases, cystic kidney diseases, kidney stones and use of alpha-glucosidase inhibitors are associated with kidney cancer.

Pneumatosis cystoides intestinalis

Summary Pneumatosis cystoides intestinalis is a rare disease with an acute or subacute clinical presentation. Here, we present two cases seen at our institution over a 5-year period. The first patient underwent emergent laparotomy due to abdominal extraluminal free air caused by ruptured pneumatosis cystoides intestinalis, which may be related to the use of alpha-glucosidase inhibitors. No perforation of the ascending colon was identified during the operation. Multiple sigmoid pneumocysts mimicking colonic polyposis were found in the second patient, who underwent sigmoidectomy for excluding colonic malignancy. We emphasize the importance of correct diagnosis of pneumatosis cystoides intestinalis and optimal management to prevent unnecessary surgical treatment.

Effects of a late evening snack combined with α‐glucosidase inhibitor on liver cirrhosis

A late evening snack (LES) is recommended for protein-energy malnutrition in patients with liver cirrhosis. However, many cases of liver cirrhosis have accompanying impaired glucose tolerance and there are concerns that LESs might aggravate glucose intolerance. In this study, we concomitantly used an alpha-glucosidase inhibitor with a LES and examined the effects on glucose tolerance. In addition, we examined whether or not there was an improvement in energy metabolism by slowing glucose absorption with the concomitant use of the alpha-glucosidase inhibitor. The subjects were 11 patients with liver cirrhosis. From before the study, all the patients had been taking a LES supplementation with a branched-chain amino acid (BCAA)-enriched nutrient mixture. The patients were started on the concomitant use of alpha-glucosidase inhibitor (0.2 mg) taken just prior to the LES. The change of glucose tolerance and energy metabolism were examined using a 75-g oral glucose tolerance test and indirect calorimetry. One week and three months after the start of the concomitant use of the alpha-glucosidase inhibitor, the area under the concentration curve for plasma glucose was significantly decreased. Three months after the concomitant use, the non-protein respiratory quotient was significantly improved. There were no serious side effects during the follow-ups. The concomitant use of the alpha-glucosidase inhibitor use with LES showed the possibility of improving glucose tolerance and energy metabolism. In patients with impaired glucose tolerance, the concomitant use of an alpha-glucosidase inhibitor with LES might be a useful measure for nutritional management.

Who should benefit from the use of alpha-glucosidase inhibitors?

Although most commonly used drugs such as biguanides, sulfonylureas, and more recently, thiazolidinediones, are effective in controlling fasting hyperglycemia, a high percentage of patients have sustained elevated hemoglobin A(1c) because of persistent elevation of postprandial plasma glucose (PPPG). alpha-Glucosidase inhibitors (AGIs) specifically target PPPG. AGIs have been shown in several randomized controlled trials to be effective in controlling blood glucose, whether they are used as monotherapy or in combination with other antidiabetic medications. Among the AGIs, acarbose has also been shown to decrease the risk of progressing to diabetes in subjects with impaired glucose tolerance (IGT). Studies have also suggested that acarbose could decrease the risk of cardiovascular disease, both in IGT and in diabetes. Furthermore, AGIs are very safe and are nontoxic drugs. Their only side effects are gastrointestinal, such as flatulence and diarrhea; however, these can be minimized by the "start low, go slow" approach. AGIs should be considered whenever postprandial hyperglycemia is the dominant metabolic abnormality.

Additive contribution of multiple factors in the development of pneumatosis intestinalis: a case report and review of the literature

We describe a 53-year-old patient with dermatomyositis, who developed pneumatosis intestinalis (PI) accompanied by pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema of the neck. The development of PI in our patient was possibly attributed to the effect of factors such as dermatomyositis, corticosteroids, methotrexate, and alpha-glucosidase inhibitor (AGI). The coexistence of multiple factors associated with PI might enhance the risk of developing PI, even though each of them alone is not sufficient to induce it. In particular, the use of AGIs for patients treated with immunosuppressive agents such as corticosteroids requires evaluation.

Cardiovascular disease in the JCR:LA-cp rat.

The JCR:LA-cp rat is one of a number of strains that carry the mutant autosomal recessive cp gene. Animals, of all strains, that are homozygous, for the gene (cp/cp) become obese, insulin resistant, and hypertriglyceridemic. Heterozygotes or homozygous normal rats (+/+) are lean and metabolically normal. The JCR:LA-cp rat is unique in the development of a frank vasculopathy with atherosclerotic lesions and associated ischemic myocardial lesions. The cardiovascular disease is strongly correlated with the hyperinsulinemia, which develops as the animals mature from 4 to 8 weeks of age. The hyperinsulinemia can be decreased by marked food restriction, ethanol consumption, or reduction of the postprandial glucose and insulin responses through the use of alpha-glucosidase inhibitors. Any treatment that reduces plasma insulin levels is associated with a reduction in cardiovascular disease. In contrast, a reduction in plasma triglyceride concentrations, alone, has no effect on end-stage lesions. JCR:LA-cp rats, particularly those that are cp/cp, are, however, sensitive to cholesterol in the diet, unlike other strains that are highly resistant. Further, the rats have abnormal vascular smooth muscle cells that, especially in the cp/cp animals, are hyperplastic and activated and migrate into the intimal space. Our findings suggest that susceptibility to cardiovascular disease requires hypermsulinemic stress coupled with excessive dietary intake and the presence of one or more other necessary, but not sufficient, genetic factors. One of these may be a genetic abnormality of vascular smooth muscle cells. A similar situation may occur in humans.

Potential of alpha-glucosidase inhibitors in elderly patients with diabetes mellitus and impaired glucose tolerance.

The prevalence of diabetes mellitus (DM) among the elderly, who constitute > 20% of the population in developed countries, is high (up to 40%). Indeed, elderly people represent the bulk (approximately 50%) of the diabetic population. There is much evidence that better glycaemic control can reduce the morbidity associated with this disease. alpha-Glucosidase inhibitors are well tolerated in the treatment of DM in this population. They reduce postprandial hyperglycaemia and have a moderate effect on fastign plasma glucose levels, resulting in a significant reduction in glycated haemoglobin (HbA1C) levels. alpha-Glucosidase inhibitors can be used either as monotherapy or in combination with other oral hypoglycaemic agents or insulin. The good safety profile of these drugs makes them suitable for use in elderly patients with type 2 (non-insulin-dependent) DM, because they can achieve substantial metabolic improvements without any additional risks. Thus, the use of alpha-glucosidase inhibitors should be considered: (i) as a first-choice treatment in newly diagnosed patients; (ii) in individuals whose DM is not well controlled with any other type of treatment; (iii) as an alternative to sulphonylureas or biguanides in patients at risk from hypoglycaemia or lactic acidosis, respectively. Despite the numerous potential advantages of alpha-glucosidase inhibitors in elderly patients with type 2 DM, there is a lack of studies focusing specifically on that population. However, such studies are under way. In addition, the potential of alpha-glucosidase inhibitors in the prevention of type 2 DM and/or on macrovascular disease is currently under study.

A strategy for anti-viral intervention: the use of alpha-glucosidase inhibitors to prevent chaperone-mediated folding of viral envelope glycoproteins.

A strategy for anti-viral intervention: the use of alpha-glucosidase inhibitors to prevent chaperone-mediated folding of viral envelope glycoproteins.

Management of insulin-dependent diabetes mellitus.

Insulin therapy has been lifesaving for patients with insulin-dependent diabetes mellitus. Unfortunately, longer lifespan has unmasked microvascular, neurological and macrovascular complications that result in profound morbidity and increased mortality. Driven by the conviction that better physiological control of glycaemic levels will prevent and/or ameliorate long term complications, and by the desire to make diabetes care as user-friendly as possible, clinical research efforts have led to the development of new treatment methods with the aim of achieving near normal metabolic control. Such methods include the use of self monitoring, multiple daily insulin injection regimens, external and implantable insulin pumps, and whole organ pancreas and isolated islet cell transplantation. In addition, dietary manipulation, including the use of alpha-glucosidase inhibitors, has played a role in controlling glycaemia.

Alpha-glucosidase inhibition and timing of preprandial insulin in patients with insulin-dependent diabetes mellitus (IDDM)

Bay-m-1099, a new alpha-glucosidase inhibitor, was given along with insulin immediately before standard breakfasts, lunches and dinners to nine insulin-dependent diabetic patients to determine whether this combination therapy would produce postprandial glycemic control comparable to that achieved when insulin alone was administered 30 min prior to eating. To avoid potential hypoglycemia, 20% less insulin (0.12 vs. 0.15 U/kg) was given with Bay-m-1099. Despite plasma free insulin concentrations which were less than those observed when insulin alone was given (9.4 +/- 1.0 vs. 12.8 +/- 1.6 microU/ml/min, area under curves for all meals), postprandial hyperglycemia (area under curve) was not significantly different (P greater than 0.1) when insulin plus Bay-m-1099 was administered immediately before each meal (124 +/- 26 mg/ml/min) than when insulin was administered 30 min before each meal (113 +/- 17 mg/ml/min). Thus, the combination of immediate preprandial administration of an alpha-glucosidase inhibitor along with insulin resulted in glycemic control comparable to that achieved when more insulin was taken 30 min prior to eating. We conclude that use of alpha-glucosidase inhibitors could lessen the inconvenience of intensive insulin regimens by permitting patients to take their insulin immediately before eating and thus result in greater patient compliance.