No abstract available.
Adamantane ; Humans ; Nitriles ; Pyrrolidines

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

While there are many therapies for type 2 diabetes are available including insulin secretagogues, insulin sensitizers and exogenous insulin, many patients are unable to reach recommended therapeutic targets. Incretin-based therapies have recently been introduced into clinical practice, and these novel therapies may make it possible to achieve improved glycemic control either with no weight gain (dipeptidyl peptidase-4 [DPP-4] inhibitors sitagliptin and vildagliptin, or with weight loss (glucagon-like peptide-1 [GLP-1] mimetics exenatide and liraglutide). This article aims to provide an overview of efficacy and safety data regarding incretinbased clinical trials in type 2 diabetic patients, and propose a systematic approach to treatment including patient selection and optimal treatment combination. In addition, preclinical data suggest that incretin-based therapies may also preserve-cell function. Therefore, these agents hold out promise of a truly disease-modifying therapy that would target the progressive nature of type 2 diabetes. Additional clinical trials will be required to test such hypothesis.
Adamantane ; Diabetes Mellitus, Type 2 ; Humans ; Incretins ; Insulin ; Nitriles ; Patient Selection ; Peptides ; Pyrazines ; Pyrrolidines ; Sitagliptin Phosphate ; Triazoles ; Venoms ; Weight Gain ; Weight Loss

New therapeutics for type 2 diabetes using incretin hormone were introduced recently. Incretin-based therapies consist of two types: GLP-1 agonists mainly acting on the GLP-1 receptor and dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors). The former is resistant to DPP-4 and injectable. The latter is oral medications raising endogenous GLP-1 by inhibiting the degrading enzyme DPP-4. The incretin based therapies are promising and more commonly used due to their action and safety profile. Stimulation of insulin secretion by these drugs occurs in a glucose-dependent manner. Incretin based therapies have low risk for hypoglycemia. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and vildagliptin.
Adamantane ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Hypoglycemia ; Incretins ; Insulin ; Nitriles ; Peptides ; Pyrazines ; Pyrrolidines ; Receptors, Glucagon ; Triazoles ; Venoms ; Glucagon-Like Peptide-1 Receptor ; Liraglutide ; Sitagliptin Phosphate

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

Adamantane ; therapeutic use ; Amantadine ; therapeutic use ; Antiviral Agents ; therapeutic use ; Child ; Guanidines ; Humans ; Influenza, Human ; drug therapy ; prevention & control ; Pyrans ; Rimantadine ; therapeutic use ; Sialic Acids ; therapeutic use ; Zanamivir

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

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

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

If the type 2 diabetes is left untreated, it can eventually be lead to vascular complications, including nephropathy, retinopathy, neuropathy, coronary heart disease, and CVA. The current antidiabetic drugs are all generally effective in the medium term, not effective eventually. In addition, they may also be associated with an increased risk of hypoglycemia, weight gain, and gastrointestinal intolerance. The dipeptidyl peptidase 4 (DPP-4) inhibitors control elevated blood glucose by increasing active glucagon- like peptide-1 (GLP-1), increasing insulin secretion and inhibiting glucagon secretion. The DPP-4 inhibitors, such as vildagliptin (Galvus) and sitagliptin (Januvia), have shown clinically significant HbA1c reductions up to 2 years of treatment and many potential advantages including a low risk of hypoglycemia, but no effect on body weight. They are used as monotherapy and also in combination with metformin or thiazolidinedione or sulfonylureas and are suitable for once-daily oral dosing to treat patients with the type 2 diabetes mellitus. The thiazolidinediones are agonists for peroxisome proliferator-activated receptor gamma (PPAR-gamma) and lowering blood glucose primarily by increasing insulin sensitivity in peripheral tissues. Rosiglitazone is widely used as monotherapy or in fixed dose combinations with either metformin or glimepiride to treat patients with the type 2 diabetes mellitus, but its effect on cardiovascular morbidity and mortality has not been determined. Dr. Nissen assisted that rosiglitazone should be associated with a significant increase in the risk of myocardial infarction. This review focused on the clinical effect of DPP-4 inhibitors and the relations between rosiglitazone and the risk of myocardial infarction.
Adamantane ; Blood Glucose ; Body Weight ; Coronary Disease ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Glucagon ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Metformin ; Myocardial Infarction ; Nitriles ; PPAR gamma ; Pyrazines ; Pyrrolidines ; Sitagliptin Phosphate ; Sulfonylurea Compounds ; Thiazolidinediones ; Triazoles ; Weight Gain