BACKGROUND: Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats. METHODS: The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols. RESULTS: HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide. CONCLUSION The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.
1-Butanol/chemistry* ; Administration, Oral ; Animals ; Diabetes Mellitus, Experimental/drug therapy* ; Dose-Response Relationship, Drug ; Hypoglycemic Agents/chemistry* ; Male ; Periploca/chemistry* ; Phytochemicals/chemistry* ; Plant Extracts/chemistry* ; Rats ; Rats, Sprague-Dawley ; Streptozocin/adverse effects*

With the increasing incidence of diabetes mellitus in China, hypodermic injection of artificial insulin to control blood sugar has been popularized. Insulin pen needles are widely used in hospitals, communities and families. This article attempts to explore and think about the harm and countermeasures brought about by the reuse of insulin pen needles from the perspective of medical device supervision.
China ; Diabetes Mellitus, Type 1 ; Humans ; Hypoglycemic Agents ; administration & dosage ; Injections, Subcutaneous ; instrumentation ; Insulin ; administration & dosage ; Needles

Patients with hyperglycemia are at a high risk of cardio- and cerebrovascular diseases. Diabetes patients also have poor outcomes after cerebrovascular disease development. Several classes of drugs are used for diabetes management in clinical practice. Thiazolidinedione (TZD) was introduced in the late 1990s, and new antidiabetic agents have been introduced since 2000. After issues with rosiglitazone in 2007, the U.S. Food and Drug Administration strongly recommended that trials investigating cardiovascular risk associated with new antidiabetic medications should be conducted before drug approval in the United States, to prove the safety of these new drugs and to determine their superiority to previous medications. Currently, results are available from two studies with TZD focusing on cardiovascular diseases, including stroke, and from 12 cardiovascular outcome trials focusing on major adverse cardiovascular events associated with new antidiabetic agents (four with dipeptidyl peptidase-4 inhibitors, three with sodium-glucose cotransporter-2 inhibitors, and five with glucagon-like peptide-1 analogues). These studies showed different results for primary cardiovascular outcomes and stroke prevention. It is important to determine whether prescription of TZD or new antidiabetic medications compared to conventional treatment, such as sulfonylurea or insulin, is better for stroke management. Furthermore, it is unclear whether drugs in the same class show greater safety and efficacy than other drugs for stroke management.
Cardiovascular Diseases ; Cerebrovascular Disorders ; Diabetes Mellitus ; Dipeptidyl-Peptidase IV Inhibitors ; Drug Approval ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Hypoglycemic Agents ; Insulin ; Prescriptions ; Stroke ; Thiazolidinediones ; United States ; United States Food and Drug Administration

PURPOSE: Cardiovascular adverse events (AEs) after use of dipeptidyl peptidase-4 (DPP4) inhibitors have been reported and suspected since the launch of DPP-4 inhibitors in 2006. However, few studies have investigated the association between cardiovascular AEs and DPP-4 inhibitors. The objective of this study is to detect the signals of cardiovascular AEs after use of DPP-4 inhibitors by analyzing the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). MATERIALS AND METHODS: Data on the use of oral antidiabetic drugs from 2008 to 2016 were extracted from KIDS-KD, and analyzed descriptively. Data mining was conducted by calculating three indices, which were proportional reporting ratios, reporting odds ratios, and information components, to detect signals from use of all oral antidiabetic drugs including DPP-4 inhibitors. Then, the suspected adverse drug reactions (ADRs) were confirmed by signal detection, and drug label information between the Korea Ministry of Food and Drug Safety and the U.S. Food and Drug Administration were compared. RESULTS: Cardiovascular AEs after taking DPP-4 inhibitors were detected in only three (1.0%) out of a total of 307 AE reports. Two of the three cardiovascular AEs were reported after using sitagliptin and one using gemiglipitin, but these were not statistically significant. CONCLUSION: Analysis of spontaneous ADR reports data on the use of DPP-4 inhibitors could not showed the association between DPP-4 inhibitors and cardiovascular AEs, due to a small number of cardiovascular AEs reports.
Cardiovascular Diseases ; Data Mining ; Drug-Related Side Effects and Adverse Reactions ; Hypoglycemic Agents ; Korea ; Odds Ratio ; Pharmacovigilance ; Sitagliptin Phosphate ; United States Food and Drug Administration

INTRODUCTIONWe aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.

METHODSThis was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.

RESULTSIn total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.

CONCLUSIONOur findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.

Adolescent ; Adult ; Aged ; Blood Glucose ; drug effects ; Blood Pressure ; Body Mass Index ; Body Weight ; Canagliflozin ; administration & dosage ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Glomerular Filtration Rate ; Hemoglobins ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; Least-Squares Analysis ; Male ; Middle Aged ; Osmosis ; Retrospective Studies ; Singapore ; Sitagliptin Phosphate ; administration & dosage ; Systole ; Treatment Outcome ; Young Adult

In 2008, the United States Food and Drug Administration issued guidance which mandated long-term cardiovascular outcome trials (CVOTs) to assess the safety of new antidiabetic drugs for type 2 diabetes. Since 2008, three CVOTs that have studied dipeptidyl peptidase-4 (DPP-4) inhibitors and four CVOTs of a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) have been reported. Each of the completed CVOTs showed the noninferiority of respective drugs to placebo for primary CV composite endpoint. Among them, liraglutide and semaglutide showed a reduction of major adverse cardiovascular events. However, the mechanisms for the observed cardiovascular differences between DPP-4 inhibitors and GLP-1RA, and across individual GLP-1RA are not clearly understood. Therefore, this review will summarize the CVOTs of the DPP-4 inhibitors and GLP-1RA, interpretation of cardioprotective results of incretin-based therapy and the possible mechanism of action.
Diabetes Mellitus, Type 2 ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Hypoglycemic Agents ; Incretins* ; Liraglutide ; United States Food and Drug Administration

Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.
Administration, Oral ; Animals ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diet, High-Fat* ; Glucose ; Glucose Tolerance Test ; Homeostasis ; Hyperglycemia ; Hypoglycemic Agents ; Insulin Resistance ; Metformin ; Rats* ; Streptozocin* ; Zinc

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; Gene Expression ; drug effects ; Glucosephosphate Dehydrogenase ; genetics ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; genetics ; metabolism ; Iridoid Glucosides ; administration & dosage ; analysis ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Rehmannia ; chemistry ; Suppressor of Cytokine Signaling 3 Protein ; genetics ; metabolism

Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography (FFA) remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.
Administration, Oral ; Contrast Media ; adverse effects ; Diabetes Mellitus, Type 2 ; diagnostic imaging ; drug therapy ; Diabetic Retinopathy ; diagnostic imaging ; Fluorescein Angiography ; adverse effects ; methods ; Humans ; Hypoglycemic Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; Metformin ; therapeutic use

The present study aimed at exploring the therapeutic potential of standard extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral administration of BCE at doses of 70, 140, and 280 mg·kg, to the normal rats and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out. Effects of BCE on blood glucose, body weight, and a range of serum biochemical parameters were tested, and histopathological observation of pancreatic tissues was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical composition of BCE mainly contained mangiferin, isoorientin, vitexin, isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin, and nigricanside. BCE caused a significant decrease in the concentrations of fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and increases in oral glucose tolerance, high density lipoprotein-cholesterol, and superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic β-cells protection effect and stimulation of insulin secretion from the remaining pancreatic β-cells could be observed after BCE treatment. The results indicated that BCE exhibited an excellent hypoglycemic activity, and alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and protecting pancreatic β-cells are the possible mechanisms involved in anti-diabetic activity of BCE.
Animals ; Antioxidants ; administration & dosage ; chemistry ; isolation & purification ; Blood Glucose ; metabolism ; Bombax ; chemistry ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; chemistry ; isolation & purification ; Hypolipidemic Agents ; administration & dosage ; chemistry ; isolation & purification ; Male ; Plant Extracts ; administration & dosage ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Rats ; Rats, Sprague-Dawley