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Nateglinide (Starlix): update on a new antidiabetic agent.

Nateglinide is a new oral antidiabetic agent that stimulates insulin release promptly after its pre-meal administration in a strongly glucose-dependent fashion. Because its insulinotropic effects are short in duration, nateglinide specifically targets postprandial hyperglycaemia with a low potential to elicit hypoglycaemia or sustained hyperinsulinaemia. Nateglinide has an excellent safety and tolerability profile, and its efficacy in reducing HbA1c in monotherapy (120 mg before meals) is comparable to that of metformin, sulphonylureas, thiazolidinediones or acarbose (-0.5 to -1.5%). When combined with metformin, which primarily reduces fasting glucose levels, nateglinide's effects are additive. In our clinical experience, nateglinide is a particularly good therapeutic option in newly diagnosed, treatment-naive patients; elderly patients in whom hypoglycaemia is a concern; patients with kidney failure or mild hepatic impairment; patients taking low-dose sulphonylureas who encounter problems with hypoglycaemia; and patients failing to achieve adequate glycaemic control on metformin or thiazolidinedione monotherapy.

Blood Glucose↗

Antioxidant, antidiabetic, antihyperlipidemic,reproduction stimulatory properties and safety of essential oil of Satureja Khuzestanica in rat in vivo: a oxicopharmacological study.

BACKGROUND: Satureja Khuzestanica is an endemic plant of Iran that is widely distributed in the southern part of the country. It is famous for its medical uses as an analgesic and antiseptic in folk medicine. The present study was designed to explore the toxicological and pharmacological effects of essential oil of Satureja Khuzestanica (SKEO) in vivo. MATERIAL/METHODS: The intraperitoneal LD50 of SKEO was determined. Teratogenicity was determined by administration of SKEO at doses of 500, 1000 and 1500 ppm to pregnant rats during days 6 to 015 of gestation. FRAP and TBARS assays were used to determine total antioxidant power and lipid peroxidation respectively. Diabetes and hyperlipidemia were induced by administration of streptozocin and lipid regimen in rats. SKEO (1000 ppm) was administered in drinking water for 10 days. RESULTS: SKEO is not lethal up to a dose of 2 g kg-1 in rats. In the teratogenicity test, dams of the treated group were active and did not show any signs of toxicity. A significant increase in the number of implantation and live fetuses were observed with SKEO (500 and 1000 ppm) in comparison to the control group. SKEO treatment decreased the normal blood lipid peroxidation level and increased total antioxidant power. Significant decreases in fasting blood glucose and triglyceride levels were observed with SKEO in diabetic and antihyperlipidemic rats respectively. CONCLUSIONS: This preliminary study indicates the safety and interesting stimulatory effect of SKEO on reproduction. The antioxidant properties of SKEO may explain its antidiabetic and triglyceride-lowering effects.

Abnormalities, Drug-Induced↗

Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure.

The purpose of the study was to find out differences between treatments of diabetes type 2 after secondary oral antidiabetic drug failure. Three different methods of treatment were compared: lispro insulin in combination with metformin, glimepiride and metformin combination or two daily doses of biphasic insulin 30/70 together with bed-time NPH insulin. The study included 87 patients with diabetes mellitus type 2 randomly distributed into 3 different treatment groups. Fasting and postprandial glucose were analyzed by enzymatic colorimetric method and HbA1c was measured by ion exchange chromatography. HbA1c significantly decreased in all three study groups. The decrease was mostly expressed among patients treated with lispro and metformin. When focused on postprandial glucose control, antihyperglycemic metformin and insulin lispro therapy has greater impact on the overall metabolic control (decrease in level of HbA1c) in comparison with the above mentioned more traditional approaches.

Administration, Oral↗

Hypoglycemic activity of some antidiabetic plants.

To assess the hypoglycemic activity mechanism of some plants used empirically by the Mexican population as antidiabetics, traditional preparations of Cucurbita ficifolia, Guaiacum coulteri, Lepechinia caulescens, and Psacalium peltatum, water, tolbutamide, and Regular Insulin were administered to three groups of rabbits each: 1. Healthy rabbits with temporary hyperglycemia induced by the subcutaneous administration of glucose. 2. Rabbits with moderate diabetes (fasting glycemia 150-300 mg/dl), induced with alloxan. 3. Rabbits with severe diabetes (fasting glycemia higher than 400 mg/dl), induced with alloxan. The plant preparations had a hypoglycemic effect similar to tolbutamide in healthy and mild diabetic rabbits and had no effect in severely diabetic rabbits. These results suggest that some pancreatic function or the presence of insulin is required for the hypoglycemic activity of these plants.

Animals↗

Antidiabetic effect of a glycoside of pelargonidin isolated from the bark of Ficus bengalensis Linn.

The antidiabetic effect of a dimethoxy derivative of perlargonidin 3-O-alpha-L rhamnoside (250 mg/kg, single dose study and 100 mg/kg/day long term study) isolated from the bark of Ficus bengalensis Linn. has been compared with that of glibenclamide (2 mg/kg and 0.5 mg/kg/day respectively) in moderately diabetic rats. The single dose glycoside treatment decreased fasting blood glucose by 19% and improved glucose tolerance by 29%. The corresponding effects of glibenclamide were 25% and 66% respectively over the control values. On one-month treatment the fasting blood glucose levels went down almost to half of the pretreatment levels in both the groups and their glucose tolerance improved by 41% in glibenclamide group and by 15% in glycoside treated group. Urine sugar decreased to traces in both the groups and they appeared healthy. In vitro studies showed that insulin secretion by beta-cells was more in presence of the pelargonidin derivative than in presence of a leucocyanidin derivative, reported to be a good anti-diabetic agent.

Animals↗

Seventy-two cases of antidiabetic-induced hepatopathy treated by huatan yigan decoction.

UNLABELLED: In order to observe the therapeutic effects of Huatan Yigan Decoction ([symbol: see text] Decoction for resolving phlegm and replenishing the liver) on antidiabetic-induced hepatopathy, 129 cases were divided into two groups, 72 cases in the treatment group were administrated with Huatan Yigan Decoction and 57 cases in the control group with the liver-protecting drugs. Their liver function, plasma prothrombin time (PT), blood urea nitrogen and symptoms of the patients before and after treatment were observed during the three therapeutic courses. RESULTS: The total effective rate and cured rate of the treatment group manifested an obvious difference in comparison with those of the control group (P < 0.05 or P < 0.01). Even though the liver function, blood urea nitrogen (BUN) and symptoms in both groups were improved markedly, these indicators in the treatment group were improved more markedly than those in control group (P < 0.01). No adverse effect was found during the treatment. CONCLUSION: Huatan Yigan Decoction shows a repair action on hepatic injury.

Adult↗

[Combined therapy with insulin/gliquidone (Glurenorm) in type 2 diabetes after treatment failure using oral antidiabetic agents].

The authors evaluate treatment by a combination of insulin and gliquidone (Glurenorm) in 29 type 2 diabetics where long-term treatment with oral antidiabetics alone had failed. Within four months all patients were completely compensated from the metabolic aspect. HbA1c declined from 10.8 to 6.5, C peptide, on the other hand, increased from the original value of 1.2 ng/ml to 1.8 ng/ml. The authors did not observe any undesirable effects or hypoglycaemic states. Gliquidone is suitable for combined treatment because of its short-term effect; stimulation of endogenous secretion has a pulsed character and imitates an intensified regime. The prerequisite of success is a low dose of intermediary insulin to prevent inhibition of the central action of gliquidone.

Adult↗

Antidiabetic drugs of plant origin used in China: compositions, pharmacology, and hypoglycemic mechanisms.

The paper reviewed compositions and pharmacological effects of eight antidiabetic herbal drugs that have been approved by health regulatory agency for commercial use in China. Investigators attributed the hypoglycemic effect of these products to their ability to restore the functions of pancreatic tissues and cause an increase in insulin output, to inhibit the intestinal absorption of glucose, or to the facilitation of metabolites in insulin-dependent processes. Treatment with herbal drugs has an effect on protecting beta cells and smoothing out fluctuations in glucose levels. The use of these naturally derived agents in conjunction with conventional drug treatments such as an chemical agent or insulin permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed.

Animals↗

Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn.

S-allyl cysteine sulphoxide (SACS), a sulphur containing amino acid of garlic which is the precursor of allicin and garlic oil, has been found to show significant antidiabetic effects in alloxan diabetic rats. Administration of it at a dose of 200 mg/kg body weight decreased significantly the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase and liver glucose-6-phosphatase. It increased significantly liver and intestinal HMG CoA reductase activity and liver hexokinase activity.

Animals↗

Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex.

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.

Administration, Oral↗

[Comparative assessment of cell mechanisms of the antidiabetic action of a new organic derivative of oxovanadium(IV) and vanadyl sulfate].

The antidiabetic effect of a new organic derivative of vanadium(IV) oxide with isonicotinic acid hydrazide (compound no. 8), as manifested by the action upon the alpha and beta cell populations in Langerhans islands of the pancreas, was studied in rats with alloxane diabetes model in comparison to the analogous effect of the inorganic drug vanadyl sulfate. The hypoglycemic activity of compound no. 8 was comparable with that of vanadyl sulfate. The results of immunohistochemical and morphometric investigation showed that both preparations produced a reliable increase in the population of insulin-producing cells and a decrease in the (alloxane-enhanced) population of alpha-cells in the pancreatic islands.

Animals↗

[Inhibition of 1,2-dimethylhydrazine-induced carcinogenesis in rat gut by the antidiabetic drug Diabenol].

Diabenol, a new Russian antidiabetic drug, was used to investigate its effect on 1,2-dimethylhydrazine (DMH)-induced carcinogenesis in rat large gut. Five doses of 21 mg/kg DMH were injected at an interval of one week. Administration of 10 mg/kg diabenol with drinking water had no effect on either body mass or feed and water consumption. Yet, it was followed by a significant decrease in tumor incidence (4.22 vs. 5.77 tumors per tumor-bearers), frequency of neoplasms in the ascending colon (40.0% vs. 89.5%) and in their number (0.60% vs. 1.63 tumors per rat in a group). In the other groups, those indices tended to be still lower. Another tendency characteristic of the experimental group was a significantly high percentage of exophytic tumors (76.3% as compared with 50% in control) consisting of well-differentiated cells (47.4% and 14.7%, respectively) and with predominantly shallow invasion into the gut wall. Our results suggest the ability of the drug to inhibit DMH-induced carcinogenesis in the rat large gut.

1,2-Dimethylhydrazine↗

[Therapy with oral antidiabetic drugs].

Hyperglycemia contributes to morbidity and mortality in diabetic patients. Reaching treatment targets with regard to control of glycemia is thus a central goal in the treatment of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of oral antidiabetic drugs according to current scientific evidence.

Administration, Oral↗

[Effect of antidiabetic drug diabenol on parameters of biological age, life span and tumor development in NMRI and HER-2/neu mice].

The effect of new antidiabetic drug Diabenol [9-diethylaminoethyl-2,3-dihydroimidazo-(1,2alpha) benzimidazol dihydrochloride] on life span and spontaneous tumor incidence in NMRI and transgenic HER-2/neu mice was studied. Female NMRI and transgenic HER-2/neu mice were given diabenol with drinking water (0.1 mg/l=approx. 10 mg/kg of b.w.) 5 times a week since the age of 2 months until natural death. The treatment with the drug failed influence body weight gain dynamics, food and water consumption and the body temperature in NMRI mice. Diabenol treatment slowed down age-related disturbances in estrous function and increased life span of all and 10% most long-living NMRI mice. The treatment with diabenol inhibited spontaneous tumor incidence (mammary gland and lymphomas mainly) and increased the mammary tumor latency. Dibenol treatment slowed down age-related changes in estrous function in HER-2/neu mice, failed influence survival of these mice and slightly inhibited the incidence and decreased the size of mammary adenocarcinoma metastases into the lung. Thus, long-term treatment with diabenol is safe and non-toxic in mice. The drug increases survival and inhibits spontaneous carcinogenesis in mice

Adenocarcinoma↗

[Diabetes mellitus in elderly: geroprotective and antidiabetic properties of delta-sleep induced peptide].

UNLABELLED: Delta-sleep induced peptide (DSIP) has a wide range of positive regulator properties. It is known as antioxidant, immunomodulator, antistressor and other, that important as for diabetes, and for aging mechanisms. Aim of the study was to investigate effects of treatment by DSIP-containing drug "Deltaran" in elderly diabetic patients. MATERIALS AND METHODS: As the pilot study we examined 11 elderly diabetic patients (mean age 66.3 yr, BMI--28.5 kg/m2, duration of diabetes 12.5 yr). All patients receive 20 doses of DSIP-containing drug "Deltaran" daily. Tests was before and after 60 days after beginning treatment. Blood samples took before and after 60 minutes after standard carbohydrates breakfast. RESULTS: After treatment were observed improvement of the parameters of quality of life on SCAG scale as the impairment of recent memory (p=0.003), mood depression (p=0.019), emotional lability (p=0.002) and anxiety (p=0.000). Also were observed improvement of quality of sleep and felling between meals in treating patients (p=0.010). Another positive tendencies consist of decrease of BP (ns), increase of ABI (ns), increase of pallestesia (p=0.017), decrease of MAU frequency (p=0.011) and decrease of glycaemia levels after load (p=0.033). And also after treatment were observed decrease of basal and reactive levels in blood of growth hormone (p=0.034 and p=0.005 accord.), insulin (ns), cortisol (ns) and on the contrary increase of dehydroepiandrosterone sulfate levels (ns). Main positive change observed in patients received only diabetic diet, where was a decrease of insulin resistance and in patients with latent autoimmune diabetes (type LADA), where was a increase insulin secretion and decrease of daily dose of insulin requiring. CONCLUSIONS: The pilot trial indicate beneficial antidiabetic and geroprotective effects of DSIP-contaning drug "Deltaran" in elderly diabetic patients.

Administration, Intranasal↗

[Antidiabetic activity of Zizyphus mauritiana Lam (Rhamnaceae)].

In traditonnal medicine, several plants were used in diabetes treatment. Among them, the aqueous extract from the leaves of Zizyphus mauritiana Lam (Rhamnaceae) was studied. The extract was administrated per os to Wistar rats made diabetics either temporarily by oral glucose tolerance test (first case) or definetely by subcutaneous injection of alloxan (second case). It was observed a striking decrease of the hyperglycemic arrow (p < 0.05) in the first case, with 300 mg/kg administrated 90 minutes before starting the test. In the second case, the results obtained with a dose of 300 mg/kg once or twice a day were identical as those with glibenclamide at 0.2 mg/kg per day. So, the antidiabetic activity of Zizyphus mauritiana Lam was experimentally born out but it has to be standardized for common use.

Alloxan↗

Antidiabetic effect of Scoparia dulcis: effect on lipid peroxidation in streptozotocin diabetes.

Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. The antioxidant effect of an aqueous extract of Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India was studied in rats with streptozotocin-induced diabetes. Oral administration of Scoparia dulcis plant extract (SPEt) (200 mg/kg body weight) for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin. The aqueous extract also resulted in decreased free radical formation in tissues (liver and kidney) studied. The decrease in thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HPX) and increase in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and glutathione-S-transferase (GST) clearly show the antioxidant properties of SPEt in addition to its antidiabetic effect. The effect of SPEt at 200 mg/kg body weight was better than glibenclamide, a reference drug.

Administration, Oral↗

Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats.

The present study was aimed to evaluate the hypoglycemic efficacy in an aqueous extract of seeds of two varieties, namely a country and a hybrid variety of Momordica charantia (MCSEt1 and MCSEt2) respectively in streptozotocin (STZ) induced diabetic rats. STZ-induced diabetic rats were treated with aqueous extracts of MCSEt1 and t2 for a period of 30 days. MCSEt1 and t2 extract treatment to diabetic rats resulted in a significant reduction in blood glucose, glycosylated hemoglobin, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glycogen phosphorylase, and a concomitant increase in the levels of hemoglobin, glycogen and activities of hexokinase and glycogen synthase. These results clearly show the antidiabetic properties of Momordica charantia. Both the varieties showed safe and significant hypoglycemic effects which were more pronounced in MCSEt1 compared to MCSEt2 and glibenclamide.

Animals↗