Use Of Acarbose Research Articles

Acarbose might be associated with reduced risk of gastric cancer in patients with diabetes mellitus: A nationwide population-based cohort study.

Several epidemiologic studies have revealed a higher risk of cancer in patients with diabetes mellitus (DM) relative to the general population. To investigate whether the use of acarbose was associated with higher/lower risk of new-onset cancers. We conducted a retrospective cohort study, using a population-based National Health Insurance Research Database of Taiwan. Both inpatients and outpatients with newly onset DM diagnosed between 2000 and 2012 were collected. The Adapted Diabetes Complications Severity Index (aDCSI) was used to adjust the severity of DM. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease. A total of 22 502 patients with newly diagnosed DM were enrolled. The Cox proportional hazards regression model indicating acarbose was neutral for risk for gastroenterological malignancies, when compared to the acarbose non-acarbose users group. However, when gastric cancer was focused, acarbose-user group had significantly lowered HR than non-acarbose users group (p = 0.003). After adjusted for age, sex, cancer-related comorbidity, severity of DM, and co-administered drugs, the HR of gastric cancer risk was 0.43 (95% CI = 0.25-0.74) for acarbose-user patients. This long-term population-based study demonstrated that acarbose might be associated with lowered risk of new-onset gastric cancer in diabetic patients after adjusting the severity of DM.

Machine learning-based prediction of off-pump coronary artery bypass grafting-associated acute kidney injury.

The cardiac surgery-associated acute kidney injury (CSA-AKI) occurs in up to 1 out of 3 patients. Off-pump coronary artery bypass grafting (OPCABG) is one of the major cardiac surgeries leading to CSA-AKI. Early identification and timely intervention are of clinical significance for CSA-AKI. In this study, we aimed to establish a prediction model of off-pump coronary artery bypass grafting-associated acute kidney injury (OPCABG-AKI) after surgery based on machine learning methods. The preoperative and intraoperative data of 1,041 patients who underwent OPCABG in Chest Hospital, Tianjin University from June 1, 2021 to April 30, 2023 were retrospectively collected. The definition of OPCABG-AKI was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The baseline data and intraoperative time series data were included in the dataset, which were preprocessed separately. A total of eight machine learning models were constructed based on the baseline data: logistic regression (LR), gradient-boosting decision tree (GBDT), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), random forest (RF), support vector machine (SVM), k-nearest neighbor (KNN), and decision tree (DT). The intraoperative time series data were extracted using a long short-term memory (LSTM) deep learning model. The baseline data and intraoperative features were then integrated through transfer learning and fused into each of the eight machine learning models for training. Based on the calculation of accuracy and area under the curve (AUC) of the prediction model, the best model was selected to establish the final OPCABG-AKI risk prediction model. The importance of features was calculated and ranked by DT model, to identify the main risk factors. Among 701 patients included in the study, 73 patients (10.4%) developed OPCABG-AKI. The GBDT model was shown to have the best predictions, both based on baseline data only (AUC =0.739, accuracy: 0.943) as well as based on baseline and intraoperative datasets (AUC =0.861, accuracy: 0.936). The ranking of importance of features of the GBDT model showed that use of insulin aspart was the most important predictor of OPCABG-AKI, followed by use of acarbose, spironolactone, alfentanil, dezocine, levosimendan, clindamycin, history of myocardial infarction, and gender. A GBDT-based model showed excellent performance for the prediction of OPCABG-AKI. The fusion of preoperative and intraoperative data can improve the accuracy of predicting OPCABG-AKI.

Profiles of sulfonylurea use in Diabetes Mellitus type 2: an analysis of clinical practice over the last 10 years

AimsDescribing the evolution over time in the use of sulfonylureas (SUs) and the characteristics of patients at first prescription and at interruption of treatment with SUs. MethodsRetrospective evaluation of data from the Italian Association of Diabetologists (AMD) Annals registry (2010–2020), about T2D patients who started treatment with SUs. The longitudinal probability of remaining on SUs was estimated by Kaplan Meier survival curves. ResultsSU prescription decreased from 30.7 % (2010) to 12.9 % (2020). Patients started on SU were 68.2 ± 11.2 years old, mostly males (55.5 %), with diabetes duration = 10.1 ± 8.3 years, BMI = 29.7 ± 5.5 kg/m2, and HbA1c = 8.3 ± 1.7 % [67 mmol/mol]. After one year, the probability of staying on SU was 85.4 %, 75.9 % after two years, 68.2 % after 3 years, 56.6 % after 5 years. Patients who discontinued SUs had higher BMI and HbA1c, were younger, more often males and treated with insulin. Over time, the percentage of subjects switched to metformin, DPP4i, SGLT2i, and GLP1RA increased, whereas use of glinides, glitazones, acarbose and insulin declined. ConclusionsThese data suggest a consensus, slowly, but increasingly aligning with the current National indications of dismissing SUs for the treatment of T2D. The new drugs for diabetes should represent a preferable choice in all patients who do not have specific contraindications.

Investigation of α-glucosidase and α-amylase inhibition for antidiabetic potential of agarwood (Aquilaria malaccensis) leaves extract

Diabetes mellitus is a metabolic disorder characterized by high blood sugar. The most common treatment is taking oral hypoglycemic drugs such as acarbose, but long-term use of acarbose has dangerous side effects. Thus, alternative therapies using herbal medicines are of interest to researchers. Aquilaria malaccensis leaves have been used as an herbal tea for their high antioxidant and antimicrobial activity. This research aimed to analyze the antidiabetic potential of A. malaccensis leaves extract in vitro and in silico. The research utilized a methodology that included the analysis of the inhibitory activity of α-amylase and α-glucosidase enzymes through spectrophotometry. Furthermore, the study examined the inhibition of glucose diffusion in the dialysis bag. Additionally, an in silico investigation on α-glucosidase inhibition was conducted, involving toxicity analysis of selected compounds, molecular docking, molecular dynamic simulation, and density functional theory. The results showed that chloroform extract of A. malaccensis leaves had the best result on each test parameter with an IC50 of 3.22 mg/mL for α-amylase inhibition and 3.65 mg/mL for α-glucosidase inhibition. The chloroform extract of A. malaccensis leaves is the best for inhibiting glucose diffusion in the first 30 min. All in silico models supported by density functional theory showed that some secondary metabolites of A. malaccensis leaves extract, such as 5-Hydroxy-4′,7-dimethoxyflavone and followed by epifriedelanol, are better than acarbose in terms of inhibiting α-glucosidase. Based on the results, agarwood's extract demonstrates anti-diabetic potential through the inhibition of α-amylase and exhibits a slightly superior efficacy in inhibiting α-glucosidase activity. This observation is substantiated by both in-laboratory and in-silico data.

The risk factors of diabetic ketosis and diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors: a retrospective study

ABSTRACT Background There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective study to assess the incidence rate and risk factors of Dapagliflozin-associated DK/DKA among patients with type 2 diabetes mellitus (T2DM) in China. Research Design and Methods Patients with T2DM treated with Dapagliflozin in Shanghai General Hospital were included in this retrospective analysis. Univariate and multivariate logistic regression was performed, and odds ratio (OR) and 95% confidence interval (CI) were calculated to identify the influencing factors associated with the occurrence of DK/DKA. Results A total of 1985 T2DM patients received Dapagliflozin for the first time were included. The prevalence of DK and DKA was 2.47% and 0.35%, respectively. Multivariate logistic regression identified age <45 years [OR = 2.99, 95% CI (1.45–6.17)], concomitant use of Acarbose [OR = 2.18, 95% CI (1.06–3.38)], Metformin [OR = 1.84, 95% CI (1.01–3.38)], and Insulin [OR = 1.93, 95% CI (1.02–3.66)] as participating factors for DK/DKA. The 1:4 matched subset sensitivity analysis further confirmed the risk factors of Dapagliflozin-associated DK/DKA. Conclusions Age less than 45 years, concomitant use of Acarbose and insulin were risk factors for Dapagliflozin-associated DK/DKA. Clinicians should watch out for high-risk features among patients with SGLT2i prescription.

System Dynamic Model Simulates the Growth Trend of Diabetes Mellitus in Chinese Population: Implications for Future Urban Public Health Governance.

Objectives: To simulate the growth trend of diabetes mellitus in Chinese population. Methods: The system dynamic modeling methodology was used to establish a population prediction model of diabetes with or without cardiovascular diseases. Lifestyle therapy and the use of metformin, acarbose, and voglibose were assumed to be intervention strategy. The outcomes will be examined at 5, 15, and 30years after 2020. Results: The projected number of diabetic population in China would increase rapidly from 141.65 million in 2020 to 202.84 million in 2050. Diabetic patients with cardiovascular disease would rapidly increase from 65.58 million in 2020 to 122.88 million by 2050. The annual cost for the entire population with diabetes mellitus in China would reach 182.55 billion by 2050. When the treatment of cardiovascular disease was considered, expenditure was 1.5-2.5-fold higher. Lifestyle therapy and the use of metformin, acarbose and voglibose could effectively slow the growth of the diabetic population. Conclusion: The diabetic population in China is expected to increase rapidly, and diabetic patients with cardiovascular disease will increase greatly. Interventions could delay it.

Risk Factors of Pancreatic Cancer in Patients With Type 2 Diabetes Mellitus: The Hong Kong Diabetes Study.

ContextDiabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors.ObjectiveThe present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study.MethodsThis was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed.ResultsThis study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01-1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30-2.81; P < .001), chronic kidney disease (HR: 1.81; 95% CI, 1.25-2.64; P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35-3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond.ConclusionDiabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs.

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update.

Diabetes mellitus (DM) and heart failure (HF) are two chronic disorders that affect millions worldwide. Hyperglycemia can induce excessive generation of highly reactive free radicals that promote oxidative stress and further exacerbate diabetes progression and its complications. Vascular dysfunction and damage to cellular proteins, membrane lipids and nucleic acids can stem from overproduction and/or insufficient removal of free radicals. The aim of this article is to review the literature regarding the use of antidiabetic drugs and their role in glycemic control in patients with heart failure and oxidative stress. Metformin exerts a minor benefit to these patients. Thiazolidinediones are not recommended in diabetic patients, as they increase the risk of HF. There is a lack of robust evidence on the use of meglinitides and acarbose. Insulin and dipeptidyl peptidase-4 (DPP-4) inhibitors may have a neutral cardiovascular effect on diabetic patients. The majority of current research focuses on sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. SGLT2 inhibitors induce positive cardiovascular effects in diabetic patients, leading to a reduction in cardiovascular mortality and HF hospitalization. GLP-1 receptor agonists may also be used in HF patients, but in the case of chronic kidney disease, SLGT2 inhibitors should be preferred.

The effect of additional acarbose on metformin-associated artificially high 18F-Fluorodeoxyglucose uptake in positron emission tomography/computed tomography.

Metformin causes diffuse and intense fluorodeoxyglucose (FDG) uptake more frequently in the colon and less frequently in the small intestine. In this study, we aimed to investigate the effect of simultaneous use of acarbose and metformin on FDG uptake in positron emission tomography/computed tomography (PET/CT), which has not been investigated previously. Totally 145 patients with amedian age of 65years (range: 18-80years), who underwent FDG PET/CT in the Department of Nuclear Medicine of Erciyes University Medical School between 2018 and 2021, were involved in the study. The patients undergoing PET/CT were categorized as metformin plus acarbose users (group MA), metformin users (group M), and control subjects without diabetes (group C). The maximum and mean standard uptake values (SUVmax and SUVmean) of FDG uptake of the all intestine segments were measured separately. The number of participants in each group was 35, 51 and 59 in group MA, group M and group C, respectively. The FDG uptake of all intestine was significantly higher in group MA and group M than in group C. The FDG uptake of ascending, transverse, descending, and sigmoid colon was significantly lower in group MA than in group M. The FDG uptake of the small intestine was not different between group MA and group M. The FDG uptake of the rectum was lower in group MA than group M and it was significant for SUVmean, but not significant for SUVmax. The addition of acarbose to metformin therapy decreased SUV and artificially high FDG uptake in the colon and may be an alternative recommendation to discontinuing metformin in patients going to PET/CT imaging.

A Combination Approach in Inhibiting Type 2 Diabetes-Related Enzymes Using Ecklonia radiata Fucoidan and Acarbose.

Although there are chemotherapeutic efforts in place for Type 2 diabetes mellitus (T2DM), there is a need for novel strategies (including natural products) to manage T2DM. Fucoidan, a sulphated polysaccharide was extracted from Ecklonia radiata. The integrity of the fucoidan was confirmed by structural analysis techniques such as FT-IR, NMR and TGA. In addition, the fucoidan was chemically characterised and tested for cell toxicity. The fucoidan was investigated with regards to its potential to inhibit α-amylase and α-glucosidase. The fucoidan was not cytotoxic and inhibited α-glucosidase (IC50 19 µg/mL) more strongly than the standard commercial drug acarbose (IC50 332 µg/mL). However, the fucoidan lacked potency against α-amylase. On the other hand, acarbose was a more potent inhibitor of α-amylase (IC50 of 109 µg/mL) than α-glucosidase. Due to side effects associated with the use of acarbose, a combination approach using acarbose and fucoidan was investigated. The combination showed synergistic inhibition (>70%) of α-glucosidase compared to when the drugs were used alone. The medicinal implication of this synergism is that a regimen with a reduced acarbose dose may be used, thus minimising side effects to the patient, while achieving the desired therapeutic effect for managing T2DM.

Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus.

AimsType 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID‐19). The effect of T2DM medications on COVID‐19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID‐19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID‐19 patients with T2DM during hospitalization.MethodsWe continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID‐19 and treated with different combinations of diabetes medications.ResultsWe found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual‐use patients, 19 (95.0%) survived.ConclusionOur analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.

Network Meta-analysis of the Therapeutic Effects of Hypoglycemic Drugs and Intensive Lifestyle Modification on Impaired Glucose Tolerance

PurposeIn the Guidelines for the Prevention and Control of Type 2 Diabetes in China (2017 edition), intensive lifestyle interventions are recommended for preventing the progression of impaired glucose tolerance (IGT) to type 2 diabetes mellitus. Acarbose and metformin can also be considered if intensive lifestyle modification has been ineffective for 6 months. But the effects of intensive lifestyle modification and glucose-lowering drug interventions that work best in the population with IGT are unclear. This network meta-analysis assessed the effectiveness of intensive lifestyle modification, acarbose, and metformin in treating populations with IGT. MethodsWe systematically searched both Chinese- and English-language databases, including China Knowledge, the Cochrane Library, Embase, PubMed, VIP, and Wanfang, for articles published between database inception and September 2019. Randomized, controlled clinical trials in patients with IGT treated with acarbose, metformin, and intensive lifestyle modification were assessed for eligibility. The data from all included studies were evaluated by 2 reviewers independently in accordance with the Cochrane Handbook for Systematic Reviews of Intervention version 6.0. A network meta-analysis was performed by using R software version 3.6.1. FindingsThe data from 53 randomized controlled trials were included in the review, with a sample size of 21,208 patients. Compared with the control group, the use of acarbose, metformin, and/or intensive lifestyle modification was associated with reduced rates of progression to diabetes (relative risks [RRs] [95% credible intervals]: acarbose, 0.37 [0.29–0.47]; metformin, 0.39 [0.30–0.50]; intensive lifestyle modification, 0.61 [0.50–0.73]). The surface under the cumulative ranking (SUCRA) value of acarbose was 88.35%, supporting that acarbose was more effective in reducing the rate of progression to diabetes compared with controls. With acarbose, metformin, and intensive lifestyle modification, the rates of achieving a normal glucose level were increased by RR = 2.1, 1.7, and 1.2, respectively when compared with control group. The SUCRA value of acarbose was 99.69%, supporting the optimal effect of acarbose in achieving a normal blood glucose level. ImplicationsIn this meta-analysis in patients with IGT, compared with controls, acarbose and metformin were associated with decreased rates of progression to diabetes and increased rates of achieving a normal glucose level. Acarbose use was associated with an increased rate of achieving a normal glucose level, while intensive lifestyle modification was not.

Synthesis, Molecular Docking and α-Glucosidase Inhibitory Activity Study of 2,4,6-triaryl Pyrimidine Derivatives

Background: α-Glucosidase inhibitors hinder the carbohydrate digestion and play an important role in the treatment of diabetes mellitus. α-glucosidase inhibitors available on the market are acarbose, miglitol, and voglibose. However, the use of acarbose is diminishing due to related side effects like diarrhea, bloating and abdominal distension. Objectives: This study aimed to synthesize 2,4,6-triaryl pyrimidines derivatives, screen their α- glucosidase inhibitory activity, perform kinetic and molecular docking studies. Methods: A series of 2,4,6-triaryl pyrimidine derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Pyrimidine derivatives 4a-m were synthesized via a twostep reaction with a yield between 49 and 93%. The structure of the synthesized compounds was confirmed by different spectroscopic techniques (IR, NMR and MS). The in vitro α-glucosidase inhibition activities of the synthesized compounds 4a-m was also evaluated against Saccharomyces cerevisiae α-glucosidase. Results and Discussion: The majority of synthesized compounds had α-glucosidase inhibitory activity. Particularly compounds 4b and 4g were the most active compounds with an IC50 value of 125.2± 7.2 and 139.8 ± 8.1 μM respectively. The kinetic study performed for the most active compound 4b revealed that the compound was a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with Ki of 122 μM. The molecular docking study also revealed that the two compounds have important binding interactions with the enzyme active site. Conclusion: 2,4,6-triarylpyrimidine derivative 4a-m were synthesized and screened for α- glucosidase inhibitory activity. Most of the synthesized compounds possess α-glucosidase inhibitory activity, and compound 4b demonstrated the most significant inhibitory action as compared to acarbose.

Hepatic and cardiovascular safety of acarbose among type 2 diabetes patients with end-stage renal disease: A nationwide population-based longitudinal study

AimTo assess the relationship between acarbose and hepatotoxicity, cardiovascular disease (CVD), and mortality among type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). Methods32,531 T2D patients with ESRD were identified from Taiwan’s National Health Insurance Research Database in 2000~∼2012 and followed up until 2013. 19.3% of subjects were newly initiated with acarbose during the follow-up. The use of acarbose was quantified as the numbers of the 30-day drug’s supplies and dosages (measured by defined daily doses; DDDs), respectively. Time-varying Cox models were applied to evaluate the association of acarbose use with hepatic, cardiovascular and mortality outcomes, with adjustment for patients’ demographics, comorbidities, diabetes severity, and co-medications. ResultsFor each 30-day supply increase in acarbose exposure, the risks of hepatic injury, composite CVD events, and all-cause mortality were significantly lowered by 9% (95% confidence interval: 6–12%), 7% (6–7%) and 7% (7–8%), respectively, while for each 30-day DDD increase in acarbose exposure, the risks for three aforementioned outcomes were significantly reduced by 45% (33–54%), 33% (29–36%) and 35% (32–39%), respectively. In subgroup analyses, the favorable study outcomes of acarbose use were more apparent among patients with more severe diabetes, a longer diabetes duration, or absence of established CVD at baseline. ConclusionAcarbose used in real-world T2D patients with ESRD may have hepatic and cardiovascular safety.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial.

Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60mmol/mol to 7.1% or 54mmol) at 6 months compared to baseline, and to placebo (p<0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p=0.037, p=0.048, and p=0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p=0.031, p=0.037, and p=0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Treatment Options for Patients with Type 2 Diabetes Mellitus during the Fasting Month of Ramadan

During Ramadan, Muslims fast from sunrise (Sahur) to sunset (Iftar) and are required to abstain from food and fluids, including oral and injectable medications. Patients with diabetes who fast during Ramadan are at risk of developing hyperglycemia with increased risk of ketoacidosis, hypoglycemia, dehydration and thrombosis. Pre-Ramadan education and preparation of a fasting patient are essential to reduce severe complications. This review paper summarizes studies to date on oral and injectable medications available for patients with type 2 diabetes during Ramadan fasting, as well as recommendations on management of these patients during Ramadan. Although there is limited data on the use of Metformin, Acarbose and Thiazolidinedione in Ramadan, they appear to be safe. Sulphonylurea, especially Glibenclamide, is associated with higher risk of hypoglycemia during Ramadan fasting, hence may need adjustment in dosing and timing. The incretin group and SGLT2 inhibitor use during Ramadan fasting is associated with low risk of hypoglycemia with no increased adverse events. Insulin regimes need to be individualized for patients who fast during Ramadan.

A randomized, crossover study of the acute effects of acarbose and gastric distension, alone and combined, on postprandial blood pressure in healthy older adults

BackgroundPostprandial hypotension (PPH) occurs frequently in the elderly and patients with type 2 diabetes, and lacks a satisfactory treatment. Gastric distension and the α-glucosidase inhibitor, acarbose, may attenuate the postprandial fall in blood pressure (BP) by complementary mechanisms. We aimed to determine whether gastric distension and acarbose have additive effects to attenuate the fall in BP induced by oral sucrose.MethodsTen healthy older adults (74.0 ± 1.4 yr) had measurements of BP and superior mesenteric artery (SMA) blood flow for 120 min after receiving either (i) the ‘study drink’ of 100 g sucrose in 300 mL of water (control treatment), (ii) a 300 mL water ‘preload’ 15 min before the ‘study drink’ (distension treatment), (iii) 100 mg acarbose dissolved in the ‘study drink’ (acarbose treatment) or (iv) a 300 ml water ‘preload’ 15 min before 100 mg acarbose dissolved in the ‘study drink’ (acarbose and distension treatment).ResultsThe area under the curve (AUC)0–120min for mean arterial pressure (MAP) was greater (P = 0.005) and the maximum fall in MAP was less (P = 0.006) during treatments with acarbose. Gastric distension did not affect the MAP-AUC0–120min response to acarbose (P = 0.44) and there was no effect of gastric distension alone (P = 0.68). Both acarbose treatments attenuated the rise in SMA blood flow (P = 0.003), whereas gastric distension had no effect.ConclusionsIn healthy older adults, acarbose (100 mg), but not gastric distension, attenuates the fall in BP and rise in SMA blood flow after oral sucrose. The observations support the use of acarbose, but not gastric distension, to attenuate a postprandial fall in BP.Trial registrationThe study was retrospectively registered at (ACTRN12618000152224) on February 02nd 2018.

Abstract 509: Acarbose, but not metformin, reduces tumor burden and improves intra-tumoral immune responses in a pre-clinical breast cancer model

Abstract Finding ways to enhance T cell infiltration into tumors and boost effector function remains a critical knowledge gap that must be addressed to improve responses to immune-stimulatory therapies. Acarbose and metformin are FDA-approved drugs for the treatment of type two diabetes that display potent anti-hyperglycemic activity. A treatment strategy that decreases intra-tumoral glucose could reduce cancer cell viability and render tumors more susceptible to immunotherapy-mediated clearance. The goal of the current study was to determine if acarbose and/or metformin reduce tumor burdens and promote anti-tumor immunity in a preclinical model of breast cancer. Eight-week-old female C57BL/6 mice were orthotopically injected with EO771-Fluc mammary tumor cells then randomized to control (CTRL), CTRL+acarbose (ACA), CTRL+metformin (MET), or acarbose+metformin (ACA+MET) for four weeks. Compared to CTRL, single-agent ACA reduced primary tumor growth (50% decrease; p&amp;lt;0.001) and spontaneous lung metastases (48% decrease; p=0.035) without altering body weight. No effects of single-agent MET or the combination of ACA+MET on EO771 tumor growth or spontaneous lung metastases were observed. nanoString analysis of whole-tumors revealed increased dendritic cell-, T cell-, T helper 1 cell-, CD8+ T cell-, and exhausted CD8+ T cell-based gene signature scores in ACA compared to CTRL-fed mice. Cellular analysis revealed an ACA-induced increase in the percent of tumor-infiltrating PD-1+CD8+ T cells (p=0.042) and a trend toward decreased tumor-infiltrating myeloid-derived suppressor cells, resulting in improved CD8:MDSC ratios. The beneficial effects of ACA on intra-tumoral immunity, specifically promoting T cell immunity within the tumor microenvironment, illustrate the potential for future combined use of ACA with immunotherapies, such as PD-1 or CTLA-4 blockade. Citation Format: William J. Turbitt, Rachael M. Orlandella, Justin T. Gibson, Lyse A. Norian. Acarbose, but not metformin, reduces tumor burden and improves intra-tumoral immune responses in a pre-clinical breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 509.

Cardiovascular Benefits of Acarbose vs Sulfonylureas in Patients With Type 2 Diabetes Treated With Metformin.

Although α-glucosidase inhibitors (AGIs) have been shown to reduce the risk of myocardial infarction in patients with impaired glucose tolerance, the cardiovascular benefits of AGIs in those with type 2 diabetes (T2D) remains unclear. We compared the clinical outcomes of adding acarbose vs sulfonylureas to metformin therapy in patients with T2D. The study population was drawn from the database of the Diabetes Pay-for-Performance program in Taiwan. Sulfonylureas and acarbose were prescribed to 196,143 and 14,306 patients with T2D, respectively, from 2004 to 2015, who had been treated with metformin. A propensity score-matched cohort study was conducted. The patients were followed up for clinical adverse events of all-cause mortality and hospitalizations of major atherosclerotic events (i.e., myocardial infarction and ischemic stroke), heart failure, or hypoglycemia. A total of 14,306 propensity score-matched pairs (age, 55.8 ± 13.1 years; 47.8% men) were enrolled in the present analysis. Compared with sulfonylureas as the add-on therapy to metformin, the use of acarbose was associated with significantly lower risks of hospitalizations for major atherosclerotic events [hazard ratio (HR), 0.69; 95% CI, 0.52 to 0.91], ischemic stroke (HR, 0.68; 95% CI, 0.49 to 0.94), and hypoglycemia (HR, 0.23; 95% CI, 0.08 to 0.71), after accounting for major confounding factors. In T2D treatment, the use of acarbose as an add-on remedy to metformin was associated with lower risks of major atherosclerotic events, ischemic stroke, and hypoglycemia compared with the use of sulfonylurea as an add-on remedy.

What the results of Acarbose Cardiovascular Evaluation(ACE) Study will be

The prevalence of prediabetes is increasing rapidly in China, and with higher prevalence in coronary heart disease and hypertension patients. Diabetes can be controlled and prevented, previous studies have confirmed that lifestyle interventions and drug interventions can delay the progression of prediabetes to diabetes, and acarbose can be used for the primary prevention of cardiovascular events in impaired glucose tolerance(IGT) and diabetic patients, but benefits of drug intervention for secondary prevention of cardiovascular disease in IGT population are uncertain. The Acarbose Cardiovascular Evaluation(ACE) Study is a multicentre, randomized, placebo-controlled, double-blind study, with the aim of assessing the use of acarbose to reduce the risk of cardiovascular events and the onset of diabetes in IGT patients with cardiovascular disease in China , the results will be very meaningful and valuable for the prevention and treatment of diabetes. We will predict the results of ACE Study based on previous evidences. (Chin J Endocrinol Metab, 2017, 33: 705-708) Key words: Acarbose; Prediabetes; Cardiovascular outcome