INTRODUCTION: GUARD (vildaGliptin clinical Use in reAl woRlD) was  a  multinational,  prospective,  observational  study that assessed the effectiveness,safety  and  tolerability of vildagliptin and vildagliptin+metformin in patients with type 2 diabetes mellitus (T2DM) under real-world conditions across four  geographical  regions  (Asia,  the  Middle  East,  Central  America and Africa). The current paper discusses the results of patients with T2DM enrolled in the Philippines.
METHODS: Patients  with  T2DM  who  were  prescribed vildagliptin or vildagliptin+metformin combination therapy were enrolled and followed as per routine clinical practice for 24 ± six weeks. Primary endpoint was the change in HbA1c from  baseline  to  study  end  (week  24±6).  Key  secondary endpoints included proportion of patients reaching target HbA1c ?7.0%, incidence of hypoglycemic events, adverse events (AEs) and serious AEs (SAEs).
RESULTS: A total of 1,117 patients were included in the final analysis, 280 on vildagliptin (of these, eight patients received additional oral antidiabetes medications) and 837 on vildagliptin+metformin. At baseline, the mean (±SD) age of the enrolled population was 54.1±11.5 years, BMI 26.3±4.7 kg/m2, HbA1c 8.0±1.2% and T2DM duration 2.3±4.0 years.At  study  end,  significant  mean  (±SE)  reductions  in  HbA1c of -1.2±0.1% (p<0.0001) and -1.5±0.1% (p<0.0001) from a baseline of 7.6±1.1% and 8.1±1.2% were observed for the vildagliptin and vildagliptin+metformin group, respectively.A similar proportion of patients achieved HbA1c ?7.0% in the vildagliptin (66.1%) and vildagliptin+metformin group(62.7%). Changes in body weight and BMI from baseline to week 24±6 were statistically significant (p<0.0001) in both the vildagliptin (-1.5±0.3 kg; -0.6±0.1 kg/m2) and the vildagliptin+metformin group (-1.4±0.2 kg; -0.5±0.1 kg/m2).The incidence of hypoglycemia was low--six patients reported hypoglycemia in the vildaglipti metformin group and  none  in  the  vildagliptin  group.  Incidence  of  adverse events was also low in both the groups (vildagliptin, 8.6% and vildagliptin+metformin, 5.3%).
CONCLUSION: Vildagliptin  and  vildagliptin+metformin significantly  reduced  HbA1c  with  good  weight  control and low incidence of hypoglycemia in patients with T2DM under real-world conditions in Philippines

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Metformin ; Vildagliptin ; Diabetes Mellitus, Type 2 ; Adamantane ; Pyrrolidines ; Hypoglycemic Agents ; Nitriles ; Hypoglycemia ; Body Weight ; Asia ; Africa ; Central America

OBJECTIVETo observe the therapeutic effect of saxagliptin in a rat model of nonalcoholic fatty liver and type 2 diabetes and investigate the possible mechanism.

METHODSRats models of nonalcoholic fatty liver and type 2 diabetes established by feeding on a high glucose and fat diet and streptozotocin injection were treated with saxagliptin (daily dose of 10 mg/kg) gavage for 8 weeks, using saline as the control. After the treatment, fasting blood glucose, serum insulin, blood lipids, liver function, liver oxidative indices, and hepatic pathologies were evaluated in all the rats, and the expressions of Bcl-2 and Bax in the liver tissue were detected with immunohistochemistry and Western blotting.

RESULTSCompared with the model group, saxagliptin intervention significantly reduced blood glucose and HOMA-IR, improved the liver function and SOD activity (P<0.01), lowered the liver weight, liver index (P<0.01) and MDA level (P<0.05), and slightly lowered the body weight and blood lipids (P>0.05); AST level was similar between the normal control group and saxagliptin intervention group (P>0.05). HE and oil red staining showed obvious hepatic pathologies in the model group, and saxagliptin intervention significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver. Hepatic Bax expression significantly increased and Bcl-2 expression decreased in the model group, and these changes were reversed by saxagliptin.

CONCLUSIONSaxagliptin shows good therapeutic effect in rat models of nonalcoholic fatty liver and type 2 diabetes possibly by controlling blood glucose, lowering insulin resistance, alleviating hepatic oxidative stress and hepatocyte damage, and regulating the expression of apoptosis-related proteins.

Adamantane ; analogs & derivatives ; pharmacology ; Animals ; Blood Glucose ; Diabetes Mellitus, Type 2 ; drug therapy ; Dipeptides ; pharmacology ; Disease Models, Animal ; Hepatocytes ; cytology ; Insulin Resistance ; Lipids ; blood ; Liver ; metabolism ; pathology ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the therapeutic effect and safety of vildagliptin combined with insulin aspart injection in elderly patients with type 2 diabetes.

METHODSSixty-six elderly patients with type 2 diabetes who had poor blood glucose control with insulin aspart injection were divided into two groups to have additional Vildagliptin (50 mg, twice daily, n=36, observation group) or Acarbose (50 mg, three times a day, n=30, control group). Blood glucose (including FBG and 2hPG), HbA1C, fasting c-peptide, postprandial c-peptide, BMI and GFR were observed after 12 weeks.

RESULTSIn the observation group, FBG, 2hPG and HbA1C decreased significantly (P<0.05), fasting and postprandial c-peptide increased (P<0.05), and BMI and GFR showed no obvious changes (P>0.05). In the control group, 2hPG and HbA1C were significant lowered (P<0.05) but FBG, fasting and postprandial c-peptide, BMI or GFR showed no changes (P>0.05). Compared with those in the control group, FBG in the observation group showed a significant reduction (P<0.05), but no significant differences were found in 2hPG, HbA1C, BMI or GFR (P>0.05). No hypoglycemia occurred in the two groups during the treatment.

CONCLUSIONVildagliptin with insulin aapart injection has equivalent effect with Acarbose combined with insulin aspart injection in decreasing 2hPG and HbA1C without increasing the body weight or the risk to hypoglycemia or causing lowered GFR. Vildagliptin has better effect in decreasing FBG and improving the function of the islet cells.

Adamantane ; analogs & derivatives ; therapeutic use ; Aged ; Blood Glucose ; Diabetes Mellitus, Type 2 ; drug therapy ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; therapeutic use ; Injections ; Insulin Aspart ; therapeutic use ; Nitriles ; therapeutic use ; Pyrrolidines ; therapeutic use

BACKGROUND: Vildagliptin is believed to improve glucose variability by restoring the physiologic pattern of insulin secretion and improving beta and alpha cells' sensitivity to glucose but with less increase in insulin secretion compared to sulfonylureas resulting in similar glucose levels but with less risk of hypoglycemia.
OBJECTIVE: To compare the effect of vildagliptin and glimepiride on glucose variability among Type 2 diabetic patients not controlled on metformin alone.
METHODS: This investigation is a prospective, interventional, open-labeled, active control, parallel assignment, efficacy study that included patients with inadequate glycemic control on monotherapy with metformin, randomly assigned either to vildagliptin or glimeparide. For one month, one group took vildagliptin 50mg/tablet one tablet twice a day while the other group took glimepiride 1 mg/tablet one tablet once a day. Subjects were asked to monitor their capillary blood glucose at seven points throughout the day for 35 days.
RESULTS: A total of 18 patients were recruited for the study and randomly assigned to either of the two treatment arms. However, only 16 patients completed the study. The vildagliptin and glimepiride groups had comparable blood sugars at baseline and at the end of the study although the glimepiride group showed a steeper decline in the blood sugar levels. Subjects in both groups showed a downward trend in the blood glucose values from day one to the 35th day with comparable mean glucose values between treatments and across combinations of day and treatment. Likewise, mean postprandial incremental area under the curve (AUCpp)and mean amplitude of glycemic excursions (MAGE) were comparable across treatments and across combinations of day and treatment, although the Glimepiride group showed relatively higher MAGE values.
CONCLUSION: Vildaglipitin and glimepiride both improved glycemia of patients with uncontrolled blood sugar on monotherapy with metformin as both groups showed downward glucose trend, although vildagliptin showed relatively less abrupt glucose lowering effect suggesting lesser risk of hypoglycemia. Mean postprandial glucose excursions of the two groups were also comparable but the vildagliptin arm had lower MAGE and may suggest an improvement in both ?- and ?-cell function.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Adult ; Young Adult ; Adolescent ; Adamantane ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Glucose ; Hypoglycemia ; Insulins ; Metformin ; Nitriles ; Prospective Studies ; Pyrrolidines ; Sulfonylurea Compounds

BACKGROUND: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. METHODS: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. RESULTS: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (DeltaHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. CONCLUSION: Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.
Adamantane ; Diabetes Mellitus ; Dipeptidyl Peptidase 4 ; Fasting ; Glucose ; Hemoglobins ; Nitriles ; Plasma ; Pyrrolidines ; Retrospective Studies

No abstract available.
Adamantane ; Humans ; Nitriles ; Pyrrolidines

We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (DeltaHbA1c). The Student's t-test between good responders (GR: DeltaHbA1c > 1.0%) and poor responders (PR: DeltaHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with DeltaHbA1c. In the multivariate analysis, age (r2 = 0.006), duration of diabetes (r2 = 0.019), HbA1c (r2 = 0.296), and creatinine levels (r2 = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.
Adamantane/*analogs & derivatives/therapeutic use ; Blood Glucose/analysis ; Body Mass Index ; C-Peptide/analysis ; Creatinine/blood ; Diabetes Mellitus, Type 2/*drug therapy/pathology ; Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use ; Hemoglobin A, Glycosylated/analysis ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Multivariate Analysis ; Nitriles/*therapeutic use ; Pyrazines/*therapeutic use ; Pyrrolidines/*therapeutic use ; Retrospective Studies ; Triazoles/*therapeutic use

During past several years, a novel class of antihyperglycemic agents, dipeptidyl peptidase-4 (DPP-4) inhibitors, has become one of the most important options in the management of type 2 diabetes. These agents have unique insulinotropic actions as well as other advantages such as lower hypoglycemia and a weight-neutral effect compared to traditional insulin secretagogues. To date, 6 different DPP-4 inhibitors have been introduced: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin and gemiglitin. This review provides a summary of the clinical data for each DPP-4 inhibitor, and discusses the similarities and differences between them.
Adamantane ; Diabetes Mellitus ; Dipeptides ; Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemia ; Hypoglycemic Agents ; Incretins ; Insulin ; Nitriles ; Piperidines ; Purines ; Pyrazines ; Pyrrolidines ; Quinazolines ; Triazoles ; Uracil ; Linagliptin ; Sitagliptin Phosphate

OBJECTIVETo synthesize a (2-Hydroxypropyl)-γ-cyclodextrin-polyethylenimine/adamantane-conjugated doxorubicin (γ-hy-PC/Ada-Dox) based supramolecular nanoparticle with host-guest interaction and to identify its physicochemical characterizations and antitumor effect.

METHODSA novel non-viral gene delivery vector γ-hy-PC/Ada-Dox was synthesized based on host-guest interaction. 1H-NMR, NOESY, UV-Vis, XRD and TGA were used to confirm the structure of the vector. The DNA condensing ability of complexes was investigated by particle size, zeta potential and gel retardation assay. Cytotoxicity of complexes was determined by MTT assay in BEL-7402 and SMMC-7721 cells. Cell wound healing assay was performed in HEK293 and BEL-7404 cells. The transfection efficiency was investigated in HEK293 cells. H/E staining and cell uptake assay was performed in BEL-7402 cells.

RESULTSThe structure of γ-hy-PC/Ada-Dox was characterized by 1H-NMR, NOESY, UV-Vis, XRD, TGA. The drug loading was 0.5% and 5.5%. Gel retardation assay showed that γ-hy-PC was able to completely condense DNA at N/P ratio of 2; 0.5% and 5.5% γ-hy-PC/Ada-Dox was able to completely condense DNA at N/P ratio of 3 and 4,respectively. The cytotoxicity of polymers was lower than that of PEI25KDa. The transfection efficiency of γ-hy-PC was higher than that of γ-hy-PC/Ada-Dox at N/P ratio of 30 in HEK293 cells; and the transfection efficiency was decreasing when Ada-Dox loading was increasing. Cell uptake assay showed that γ-hy-PC/Ada-Dox was able to carry drug and FAM-siRNA into cells.

CONCLUSIONThe novel vector γ-hy-PC/Ada-Dox has been developed successfully, which has certain transfection efficiency and antitumor activity.

2-Hydroxypropyl-beta-cyclodextrin ; Adamantane ; administration & dosage ; pharmacology ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Doxorubicin ; administration & dosage ; pharmacology ; Genetic Vectors ; Humans ; Nanoparticles ; Polyethyleneimine ; Transfection ; beta-Cyclodextrins

BACKGROUND: The present study investigated the efficacy and safety of vildagliptin-metformin treatment compared to those of glimepiride-metformin treatment for type 2 diabetes. METHODS: In a randomized, open-label, comparative study, 106 patients with type 2 diabetes were enrolled. The primary endpoint was a reduction in HbA1c from baseline and secondary endpoints included fasting plasma glucose (FPG) or 2-hour postprandial glucose (2h-PPG) reduction from baseline, as well as HbA1c responder rate and HbA1c reduction according to baseline HbA1c category. RESULTS: Comparable HbA1c reduction was observed with a mean+/-standard deviation change from baseline to the 32-week endpoint of -0.94+/-1.15% in the vildagliptin group and -1.00+/-1.32% in the glimepiride group. A similar reduction in 2h-PPG (vildagliptin group 3.53+/-4.11 mmol/L vs. the glimepiride group 3.72+/-4.17 mmol/L) was demonstrated, and the decrements in FPG (vildagliptin group 1.54+/-2.41 mmol/L vs. glimepiride group 2.16+/-2.51 mmol/L) were not different between groups. The proportion of patients who achieved an HbA1c less than 7% at week 32 was 50.1% in the vildagliptin group and 56.0% in the glimepiride group. An average body weight gain of 2.53+/-1.21 kg in the glimepiride group was observed in contrast with the 0.23+/-0.69 kg weight gain noted in the vildagliptin group. A 10-fold lower incidence of hypoglycemia was demonstrated in the vildagliptin group, in addition to an absence of severe hypoglycemia. CONCLUSION: Vildagliptin-metformin treatment provided blood glucose control efficacy comparable to that of glimepiride-metformin treatment and resulted in better adverse event profiles with lower risks of hypoglycemia and weight gain.
Adamantane ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Humans ; Hypoglycemia ; Incidence ; Metformin ; Nitriles ; Plasma ; Pyrrolidines ; Sulfonylurea Compounds ; Weight Gain