Biguanide Research Articles

Impact of Initial Treatment Policies on Long-term Complications and Costs in Japanese Patients with Type 2 Diabetes: A Real-World Database Study.

Type 2 diabetes (T2D) represents a remarkable disease burden in Japan, and the cost-effectiveness of pharmacotherapy is an important consideration. In this study, we compared the long-term effects of the type of initial medication, as well as the initial frequency of clinic visits, on the occurrence of T2D-related complications. Additionally, we compared the medical costs associated with each treatment pattern. We analyzed electronic health record data collected from multiple primary care clinics in Japan. Patients were selected based on being primarily prescribed either biguanides (BG) or DPP-4 inhibitors (DPP-4i) during a 3-month baseline period, both of which are commonly used as first-choice medications in Japan. We then followed the onset of T2D-related complications and conducted survival analyses. Additionally, we calculated the accumulated medical costs up to the onset of an event or loss to follow-up, and summarized the annual costs per patient for each treatment pattern. A total of 416 Japanese patients with T2D who initiated treatment between January 2015 and September 2021 were included. The median follow-up period was 2.69years. The survival analysis showed that the use of DPP-4is and frequent visits from the beginning of treatment did not offer a benefit in suppressing the onset of complications later on. On the other hand, it was found that the annual medical costs for the group using DPP-4i with frequent visits were about 1.9 times higher than for the group using BGs with less frequent visits. The results suggest that for Japanese patients with T2D, the use of BGs along with relatively long follow-up intervals in the beginning of treatment can remarkably reduce medical costs while providing a level of complication suppression equivalent to that of the use of DPP-4is or frequent visits.

Guanidine-modified albumin-MMAE conjugates with enhanced endocytosis ability

Aiming to address the insufficient endocytosis ability of traditional albumin drug conjugates, this paper reports elegant guanidine modification to improve efficacy for the first time. A series of modified albumin drug conjugates were designed and synthesized with different structures, including guanidine (GA), biguanides (BGA) and phenyl (BA), and different quantities of modifications. Then, the endocytosis ability and in vitro/vivo potency of albumin drug conjugates were systematically studied. Finally, a preferred conjugate A4 was screened, which contained 15 BGA modifications. Conjugate A4 maintains spatial stability similar to that of the unmodified conjugate AVM and could significantly enhance endocytosis ability (p*** = 0.0009) compared with the unmodified conjugate AVM. Additionally, the in vitro potency of conjugate A4 (EC50 = 71.78 nmol in SKOV3 cells) was greatly enhanced (approximately 4 times) compared with that of the unmodified conjugate AVM (EC50 = 286.00 nmol in SKOV3 cells). The in vivo efficacy of conjugate A4 completely eliminated 50% of tumors at 33 mg/kg, which was significantly better than the efficacy of conjugate AVM at the same dose (P** = 0.0026). In addition, theranostic albumin drug conjugate A8 was designed to intuitively realize drug release and maintain antitumor activity similar to conjugate A4. In summary, the guanidine modification strategy could provide new ideas for the development of new generational albumin drug conjugates.

Current status of oral antidiabetic drug prescribing patterns based on the body mass index for Japanese type 2 diabetes mellitus patients and yearly changes in diabetologists' prescribing patterns from 2002 to 2019 (JDDM61).

Aims/IntroductionType 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients’ BMI levels.Materials and methodsOAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD‐treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI.ResultsComparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase‐4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m2. DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m2, use of BGs and sodium–glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m2, they were the third most prescribed OADs for patients with BMI >35 kg/m2 after BGs and sodium–glucose cotransporter 2 inhibitors .ConclusionsDPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients.

Ultraviolet photolysis of metformin: mechanisms of environmental factors, identification of intermediates, and density functional theory calculations

As a commonly used anti-diabetic drug, metformin (MEF) is frequently detected in different water bodies which pose a potential threat to human health and the ecological environment. In this study, oxidative degradation of MEF under ultraviolet (UV) light was studied, and its influencing factors, photolysis mechanism, and intermediates identification carried out as well. The results showed that the hydroxyl radical contributed 73% during the 6 h MEF photolysis process among the reactive oxygen species (ROS). In addition, triplet excited-state organic matter and singlet oxygen also played a role in the photolysis process. The reaction rates of hydroxyl radical and singlet oxygen with MEF are (6.45 ± 0.4) × 109 and (5.4 ± 0.7) × 106L·(mols)-1, respectively. By calculating the light screening effect of environmental factors, it is found that the presence of NO3- and Cl- had a greater excitation effect on ROS than the screening effect, and generally promoted the photolysis rates of MEF from 90.3 to 193.5% and from 16.1 to 80.6% during the 6-h reaction process, respectively. For bicarbonate and fulvic acid, the light screening effects were dominant and inhibited photolysis rates by 10-52% and 13-71%, respectively. The results demonstrated that the photoreactivity of environmental factors in water is the cause of the different photodegradation rates of MEF. The oxidative degradation product of MEF under UV light was detected by UPLC/Q-TOF as methylbiguanide (MBG), 2,4-diamino-1,3,5-triazine (2,4-DAT), biguanide (BGN), 1,1-dimethylguanidine (1,1-DiMBG), 4-amino-2-imino-1-methyl-1,2-dihydro-1, 3,5-triazine (4,2,1-AIMT), and 2-amino-4-methylamino-1,3,5-triazine (2,4-AMT). The result which showed that the primary sites of ∙OH attacked is consistent with that of density functional theory calculation. Graphical abstract.

Mining treatment patterns of glucose-lowering medications for type 2 diabetes in the Netherlands

Rationale and objectivesDifferent classes of glucose-lowering medications are used for patients with type 2 diabetes mellitus (T2DM) management. It is unclear how often these medications are prescribed in clinical practice....

1165-P: In Vitro Actions of a Novel Biguanide (BIG), NT1195, That Support Its Use in T2D

Metformin, a frontline treatment for T2D, is a BIG drug with low potency and limiting side effects. To overcome these limitations, we examined a compound library of 265 novel BIGs by screening these agents against five organic cationic transporters (OCTs) (OCTs 1, 2 and 3, PMATE and MATE1), an approach based on the need of OCTs for BIG cell entry and action. mRNA expression data from vervet monkey liver, fat and muscle showed OCT1, OCT3, PMAT and MATE1 were the predominate transporters and were used to guide our search for more potent and selective BIGs. BIG transport activity was measured by a decrease in oxygen consumption rate (OCR) in HEK 293 cells that express a single OCT and the results reported as EC50 values. Following the screening, we identified NT1195 from its EC50 transport values of 25, 5, 12, 3 and 57 uM respectively for OCT1, 2 and 3, PMAT and MATE1 when compared to those for metformin of 409, 320, 133, 288 and 5,993 uM. Other cellular effects of NT1195 were then examined in human adipocytes and myotubes, and in H4-lle liver cells. AMPK activation, a basic feature of BIG action, was increased by 6-fold over basal by NT1195 in fat cells versus a 3-fold increase by metformin; the EC50 values were respectively 78 uM and 4,928 uM. NT1195 stimulated AMPK in myotubes by 3-fold with an EC50 of 1,994 uM; metformin stimulation AMPK by 1.8-fold with an EC50 of 7,817 uM. Both agents produced a 2-fold activation of AMPK in H4-II e cells but with different EC50 values of 641 uM for NT1195 and 5,576 uM for metformin. Glucose production by H4-IIe cells was inhibited 90% by both BIGs, whereas the EC50 values were 32 nM for NT1195 and 285 uM for metformin. NT1195 inhibited lipolysis in human fat cells stimulated by isoproterenol by 90% with an EC50 of 286 uM while metformin inhibited lipolysis by 66% with an EC50 of 4,360 uM. Therefore overall, these findings demonstrate the much greater potency of NT1195 over metformin and supports its potential as an improved therapeutic for T2D. Disclosure J.N. Livingston: Consultant; Self; CohBar, Inc. Employee; Self; NovoTarg Therapeutics. J.E. Cobb: Consultant; Self; NovaTarg Therapeutics. K.K. Brown: None. K. Kavanagh: Research Support; Self; Takeda Development Centre Europe Ltd. K.W. Batchelor: None. Funding National Institutes of Health

1187-P: The Novel Biguanide NT1195 Is an Oral Antidiabetes Drug for Patients with Kidney Disease

Metformin, the most prescribed drug for T2D, has significant deficiencies in potency, pharmacokinetics (PK) and safety, especially in patients with kidney disease. Despite these deficiencies no improvements have been made to the biguanide (BIG) drug class. Novel BIGs with greater efficacy and without the risk of lactic acidosis are needed for T2D in patients with impaired renal function. A library of novel BIGs was screened for functional activity against a panel of organic cation transporters (OCTs). This OCT activity profile has allowed us to select BIGs with increased potency, improved PK properties and reduced elimination in urine. NT1195 was identified from this library and examined in more detail. This BIG is 5-10x more potent in mouse OGTT than metformin and is potent in the db:db mouse model, lowering plasma glucose after 8 days of dosing when metformin did not. NT1195 is more effective at elevating GLP-1 levels and inhibited gastric emptying in mice, where metformin did not. Improved potency alone is not sufficient to create the next generation of BIG therapeutics; it is also important to improve drug safety and to reduce the risk of lactic acidosis. Detailed PK studies in mice show that NT1195 has a 28.5h half-life (metformin = 1.97h), high levels of exposure (6x &amp;gt;metformin) and renal clearance that is 50x less than metformin. This latter finding suggests an increase in the safety of NT1195 in patients with impaired renal function, since we anticipate that NT1195 will be cleared by non-renal processes and that drug levels will not be affected by kidney disease. PK studies in cynomolgus monkeys provide similar findings for NT1195 with good exposure and a long half-life after oral administration. Also, NT1195 was found to increases glucose disposal in an IVGTT in insulin resistant monkeys. Safety studies are underway that will prepare NT1195 for a micro-dose study in T2D patients with and without kidney disease. Disclosure K.W. Batchelor: None. J.N. Livingston: Consultant; Self; CohBar, Inc. Employee; Self; NovoTarg Therapeutics. K.K. Brown: None. K. Kavanagh: Research Support; Self; Takeda Development Centre Europe Ltd. J.E. Cobb: Consultant; Self; NovaTarg Therapeutics. Funding National Institute of Diabetes and Digestive and Kidney Diseases

Investigation of a Dipeptidyl Peptidase-4 Inhibitor/Thiazolidinedione Combination Drug for Patients With Type 2 Diabetes and Poor Glycemic Control: Difficulty With Patient Enrollment

BackgroundOne of the treatment options for type 2 diabetes mellitus (DM) is a combination drug (CD) that contains the dipeptidyl peptidase-4 inhibitor (DPP4I) alogliptin (AG) together with pioglitazone (PG). This CD can improve impaired insulin secretion and insulin resistance, which are the two major pathologic factors for type 2 DM, and is also expected to increase adherence to treatment. We conducted a multicenter open-label prospective study to examine the usefulness of this CD for routine management of type 2 DM.MethodsIn type 2 DM patients with poor glycemic control who had been taking a DPP4I for ≥ 1 month, PG (15 mg/day) was added (first point). When the safety of PG was confirmed after 1 - 3 months, the DPP4I and PG were switched to the CD containing AG (25 mg) and PG (15 mg) (second point). Three months after switching to the CD was defined as the final point. Evaluation of objective findings, laboratory test results, and medication adherence was performed at these three points.ResultsNineteen subjects completed the study, but this was far short of the target (160 subjects). Compared to the first point, white blood cell count (WBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), and fasting blood glucose (FBG) all showed a significant decrease at both the second and final points. No change in medication adherence was observed throughout the study period. The most notable point about this study was the extremely small number of subjects enrolled. As a possible explanation, we considered whether the preferences of the study doctors for antidiabetic drugs differed between specialties. The study doctors were mainly gastroenterologists, followed by endocrinologists/diabetologists and cardiologists in equal numbers. As an additional investigation, we determined the percentages of specialist doctors prescribing DPP4Is, sodium-glucose cotransporter-2 inhibitors (SGLT2Is), PG, or biguanides (BGs) as the main treatment for DM in 1 month at our hospital. We found that a low percentage of endocrinologists/diabetologists prescribing PG compared to other drugs, while cardiologists prescribed PG frequently.ConclusionsIt was confirmed that the combination of DPP4I with PG was effective for the treatment of type 2 DM and improving metabolic function. Our data also showed that prescription of antidiabetic drugs differed between specialties, suggesting differences in their response to the results of various clinical studies and adverse reaction reports.

Recent advances in the role of AMP-activated protein kinase in metabolic reprogramming of metastatic cancer cells: targeting cellular bioenergetics and biosynthetic pathways for anti-tumor treatment.

Growing data indicate that tumor progression and metastasis is dependent on the reprograming of cellular metabolism. Rapidly growing cancer cells undergo metabolic stress in a harsh microenvironment. AMP-activated protein kinase (AMPK) is an energy sensing factor that regulates bioenergetics and biosynthetic pathways within the cell, but its role under metastasis is in dispute. The best studied phenotype of cancer cells is aerobic glycolysis (the Warburg effect), an increased catabolism of glucose to lactate. However, glycolysis and mitochondrial oxidative phosphorylation may operate simultaneously in cancer cells. Many tumors may switch between these pathways accordingly to the current requirements. The alterations in metabolism of cancer cells combined with the overexpression of oncogenes (c-Myc) and transcription factors (Hypoxia-inducible factor 1a) confer a great advantage to malignant cells to avoid reactive oxygen species induced apoptosis. The determination of the role of AMPK network in metabolic reprogramming of metastatic cancer cells may help to identify the selective molecular targets for efficient anti-cancer therapies. In this review, we discuss the implications of AMPK activation in metabolic reprogramming of cancer cells and we present several potential therapeutic strategies targeting cancer cell metabolism. AMPK activator, biguanide metformin, either alone or in combination with other drugs, may selectively modulate signaling pathways, expresses the chemopreventive potential and can be used in current anti-cancer approaches. However, the ambiguous data suggest that the activation of AMPK may induce multiple effects and thus potential therapeutic anti-cancer approach should be carefully considered in relation to metabolic network of cancer cell signaling and other determinants such tumor stage and origin as well.

The prescribing trend of oral antidiabetic agents for type 2 diabetes in Taiwan

The purpose of this study was to evaluate the prescription trend and pattern of oral antidiabetic (OAD) medications, which are extensively used worldwide for treating type 2 diabetes, in 2 age groups.In this population-based study, data obtained from the National Health Insurance Research Database, Taiwan, were analyzed to investigate the prescription trend of all types of OAD medications during 2005 to 2012. We used descriptive statistics to demonstrate the trend of prescription patterns stratified by age (aged 65 years and above or younger than 65).Sulfonylurea (SU) was once the most commonly used drug, but the proportion of its prescription had declined gradually (76.83% in 2005 to 63.70% in 2012). Consequently, biguanide (BG) became the most commonly used drug since 2010 (64.31% in 2005 to 74.41% in 2012). In addition, the prescriptions of thiazolidinedione decreased significantly (9.20% in 2005 to 2.86% in 2012), whereas the usage of DPP-4 inhibitor increased with time (3.73% in 2009 to 19.64% in 2012). The treatment choice of SU and α-glucosidase inhibitor (AGI) was higher in elderly patients compared with the younger population (SU: 62.70% in 2012, AGI: 12.78% in 2012). Two-drug combination therapies were the prevalent treatment choices for patients with type 2 diabetes (44.77% in 2012), particularly in the elderly group; however, ≥3 drug combination therapies increased gradually during the study period, particularly in the younger group.This descriptive study presents the change in the prescription of OAD medication for different age groups during 2005 to 2012.

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study

BackgroundType II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients.MethodsThis prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient’s demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis.ResultsThe mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p < 0.05) but not body mass index (BMI). BIG alone, or in combination with SUA and TNZ did not improve glycaemic status at follow up (p > 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up.ConclusionsStatin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity.

A Randomized, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Adding Omarigliptin to Antihyperglycemic Therapies in Japanese Patients with Type 2 Diabetes and Inadequate Glycemic Control.

IntroductionDaily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients.MethodsA 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q.w. DPP-4 inhibitor omarigliptin as add-on therapy to five different classes of orally administered AHA [sulfonylurea (SU), glinide (GL), biguanide (BG), thiazolidinedione (TZD), or α-glucosidase inhibitor (AGI)] commonly used in Japan and having different mechanisms of drug action from DPP-4 inhibitors. The trial consisted of an initial 24-week double-blind, placebo-controlled period during which patients (stratified by background AHA) were randomized to omarigliptin 25 mg q.w. or placebo, followed by a 28-week open-label period during which patients on placebo were switched to omarigliptin.ResultsAfter 24 weeks, the percentages of patients with adverse events (AEs), serious AEs, drug-related AEs, AEs of symptomatic hypoglycemia, or who discontinued from trial medication because of an AE were generally similar in the omarigliptin and placebo groups, in all background AHA strata and in the overall population. From a mean baseline HbA1c of approximately 8.0%, the placebo-adjusted least-squares mean changes from baseline ranged from −0.80% (AGI stratum) to −1.16% (TZD stratum); p < 0.001 for all background AHA strata. During the open-label period, no safety signals emerged with longer-term treatment. At week 52, the change from baseline in HbA1c in the omarigliptin/omarigliptin group was similar to that of the placebo/omarigliptin group.ConclusionsAddition of once-weekly omarigliptin to AHA therapy with an SU, GL, BG, TZD, or AGI for up to 52 weeks was generally safe and well tolerated, and provided persistent efficacy.Clinical trial registrationClinicalTrials.gov: NCT01697592.FundingMSD K.K., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0270-7) contains supplementary material, which is available to authorized users.

Dipeptidyl peptidase-4 inhibitors as preferable oral hypoglycemic agents in terms of treatment satisfaction: Results from a multicenter, 12-week, open label, randomized controlled study in Japan (PREFERENCE 4 study).

Aims/IntroductionTo compare the treatment satisfaction of four classes of oral hypoglycemic agents (OHAs): dipeptidyl peptidase‐4 (DPP‐4) inhibitors, α‐glucosidase inhibitors (αGI), biguanides (BG) and sulfonylureas (SU), which are common initial treatments for type 2 diabetes mellitus patients in Japan, and to identify the best oral hypoglycemic agent in terms of treatment satisfaction.Materials and MethodsIn this 12‐week, randomized, controlled, open‐label study, Japanese outpatients with type 2 diabetes mellitus who were naïve to pharmacological treatment were randomly assigned a DPP‐4 inhibitor, a BG., an αGI or a SU. The primary end‐point was the Oral Hypoglycemic Agent Questionnaire (OHA‐Q) total and subscale scores (treatment convenience, somatic symptoms and satisfaction) at week 4. Adherence, glycated hemoglobin (HbA1c) level and safety were also evaluated.ResultsThe DPP‐4 inhibitor group scored highest in the OHA‐Q total and all subscale scores at week 4. The total score was significantly higher in the DPP‐4 inhibitor group than in the BG or αGI groups (P = 0.0084 and 0.0147, respectively). The mean total score at week 12 was also highest in the DPP‐4 inhibitor group, with a significant difference compared with the αGI group (P = 0.0293). The mean HbA1c decreased from baseline to week 12 in all groups. The DPP‐4 inhibitor group had the highest adherence at weeks 4 and 12. A total of 11 patients reported adverse events, including one hypoglycemic event in the SU group.ConclusionsThe DPP‐4 inhibitor was the most preferable option in terms of treatment satisfaction.

Study of adverse drug reactions in patients with diabetes attending a tertiary care hospital in New Delhi, India.

The present prospective observational study was carried out in a tertiary care hospital in New Delhi, India from May 2014 to June 2015 to report adverse drug reactions (ADRs) in patients with type 2 diabetes mellitus (T2DM) using antidiabetic drugs. A total of 220 patients (121 males, 99 females) were enrolled. ADRs were recorded on the prescribed form. Causality and severity assessment was done using Naranjo's probability scale and modified Hartwig and Siegel's severity scale, respectively. Commonly prescribed drugs were biguanides, peptide hormone and sulphonylurea. A total of 26 ADRs were recorded (16 in males and 10 in females). Most commonly observed ADRs were related to endocrine and gastrointestinal system. Severity assessment of ADRs showed seven (26.9%) ADRs as moderate, and 19 (73.1%) as mild. No severe reactions were observed. ADRs were mostly related to endocrine and gastrointestinal system. More information on prescribed drugs and their side effects is required for ensuring patient safety.

The combination of dulaglutide and biguanide reduced bodyweight in Japanese patients with type 2 diabetes.

The efficacy and safety of once‐weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D) were evaluated according to subgroups defined by concomitant oral hypoglycaemic agents. This exploratory analysis included data from a randomized, open‐label, phase III study that compared dulaglutide with insulin glargine (glargine) (n = 361). The three subgroups were dulaglutide or glargine in combination with sulphonylurea (SU) alone, biguanide (BG) alone or SU and BG combined. There were no clinically relevant differences in glycated haemoglobin (HbA1c) changes among the three subgroups in the dulaglutide group; in the glargine group, a numerically greater reduction was observed in combination with BG alone compared to the other two groups (SU alone and SU + BG). Weight loss was observed with dulaglutide in combination with BG alone or with SU + BG. The incidence of adverse events among subgroups was significantly different in the glargine group but not in the dulaglutide group. Incidence of hypoglycaemia was highest in combination with SU for both treatments. For patients with T2D, dulaglutide added to concomitant BG may be more likely to result in weight loss than dulaglutide added to concomitant SU.

LISTERIA MONOCYTOGENES ADHESION TO FOOD PROCESSING SURFACES (BONING KNIVES) AND THE REMOVAL EFFICACY OF DIFFERENT SANITIZERS

The adhesion and biofilm formation of Listeria monocytogenes on new and used boning knives (handle and blade) was observed and the number of pathogens on both surfaces increased with the contact time, forming biofilm after 2h. L. monocytogenes removal with peracetic acid and hot water were effective at all contact times and concentrations evaluated. The biguanide showed lower efficiency on used surfaces, increasing the effectiveness at concentrations of 2.0%. The new blades showed a lower roughness and flattening morphology in comparison to used surfaces. In this way it was possible to observe a greater adherence on used boning knifes.

Analysis of diabetes drug application of 2012~2014 in Wujin People's Hospital of Changzhou in Jiangsu Province

Objective To understand the diabetes drug application of 2012-2014 in Wujin People's Hospital of Changzhou,and to provide reference for clinical medicine. Methods The information system in Wujin People's Hospital of Changzhou was used,anti diabetic drug use data were retrieved from 2012 to 2014 in our hospital.The sales volume of drugs,defined daily dose(DDD),drug DDDs,defined daily cost of DDDc and sorting ratio were analyzed as index. Results Consumptions of antidiabetic drugs as insulin and its analogs in our hospital were between 400-500 million yuan,occupied about 70% of the proportion,and played a leading role.Alpha glucosidase inhibitors and metformin were the main component in the oral hypoglycemic drugs,accounted for 35% and 10% respectively;biguanides of DDDs value ordering three years in a row were in the first place,the DDDs of alpha glucosidase inhibitors value ordering three consecutive annual were averagely in the third and fourth. Conclusion The clinical medication of anti diabetic drugs in Wujin People's Hospital of Changzhou is reasonable,safe and economic. Key words: Hypoglycemic Agents; Medication Systems,Hospital; Fees,Pharmaceutical; Rationalization

Recent progress in studying type 2 diabetes mellitus and tumor risk

During recent years, increasing evidences have indicated that type 2 diabetes mellitus(T2DM)might increase the risk of certain tumors; the process might be not only related with the chronic pathologic status of T2DM such as hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, status of chronic inflammation but also associated with the long-term use of anti-diabetic drugs(i.e. sulfonylureas, biguanides, glitazones, dipeptidyl peptidase-4 inhibitors, glucagon-like peptitide-1 receptor agonists), as well as the use of insulin and insulin analogues. Herewith a system review was made about the recent progress in studying T2DM and tumor risk. (Chin J Endocrinol Metab, 2015, 31: 544-547) Key words: Diabetes mellitus, type 2; Neoplasms; Drugs

Effects of Tiaozhi-Tongluo decoction combined with atorvastatin tablets on type 2 diabetes mellitus and lipid metabolism in patients with hyperlipidemia

Objective To observe the effects of Tiaozhi-Tongluo decoction combined with atorvastatin tablets on type 2 diabetes mellitus and lipid metabolism in patients with hyperlipidemia. Methods All patients were recruited into a control group and an observation group. Patients in both groups were performed diet control, reasonable exercise, and routine oral sulfonylureas and biguanides to make glucose level in a normal range. The control group was treated with atorvastatin tablets, 20 mg/d. While the observation group was treated with atorvastatin tablets plus Tiaozhi-Tongluo decoction. After both groups were treated for 6 months, the blood glucose and blood lipid level were detected for the evaluation of clinical curative effect. Results The total effective rates in the observation group and the control group were 87.5% (56/64)and 73.0% (46/63), respectively, the difference was statistically significant (χ2=4.213, P=0.040). The serum levels of total cholesterol (4.31 ± 1.11 mmol/L vs. 5.62 ± 1.34 mmol/L, t =6.004) and triglyceride (1.73 ± 0.53 mmol/L vs. 2.57 ± 1.01 mmol/L, t =5.855) in the observation group were significant lower than those in the control group. The levels of fasting plasma glucose (6.31 ± 1.64 mmol/L vs. 7.21 ± 1.71 mmol/L, t =3.027) , 2-h postchallenge plasma glucose (8.81 ± 1.39 mmol/L vs. 9.69 ± 1.55 mmol/L, t =3.370), and glycosylated hemoglobin (6.79% ± 1.61% vs. 7.96% ± 1.72%, t=3.958) in the observation group after treatment were significantly decreased than the control group (P<0.01). Conclusion Tiaozhi-Tongluo decoction combined with atorvastatin can reduce serum total cholesterol and triacylglycerol, and it is superior to atorvastatin alone in reducing lipidemia in type 2 diabetes mellitus patients with hyperlipidemia. Key words: Diabetes mellitus, type 2; Hyperlipidemias; Anticholesteremic agents; Treatment outcome; Atorvastatin; Tiaozhi-Tongluo decoction

Clinical analysis of treatment for obesity hypertension with western medicine and Chinese medicine Tong Shui San

Objective To analyze clinical effect of treatment for obesity hypertension with western medicine and Zhong Yao Wai Yong Tong Shui San, to provide a reference for clinical drugs. Methods 150 obesity hypertension patients were selected, they were divided into group A,B,C according to mathematical random method,50 cases in each group. Ammonia amlodipine was used in group A,dimethyl biguanide was used in group B,besides ammonia amlodipine and dimethyl biguanide, self- made Zhong Yao Wai Yong Tong Shui San were used in group C.Index such as insulin and blood pressure were compared in three groups. Results Rate of blood pressure control of group C was 96.00%,higher than that of group A(80.00%)and group B(82.00%), there were statistical difference(χ2= 6.495,P= 0.008;χ2= 6.215,P= 0.010);after the treatment,DBP and SBP of group C were(73.75±6.83) mm Hg and(122.66±11.46) mm Hg,better than group A and group B(all P group B> group A,there were statistical difference(all P< 0.05). Conclusion Combination of western medicine and Zhong Yao Wai Yong Tong Shui San has a good performance in improving blood pressure,blood lipids and insulin. Key words: Hypertension; Tong Shui San; Chinese medicine for external use