Oral Anti-Diabetic Agents-Review and Updates.

Diabetes is a chronic metabolic disorder with high mortality rate and with defects in multiple biological systems. Two major types of diabetes are recognized, type 1 and 2 with type 2 diabetes (T2D) being by far the more prevalent type. As diabetes affects multiple biological functions, the use of multiple drug classes having different mode of actions is required in order to optimize therapy in diabetic patients. Five major classes of oral antidiabetic agents (OHA) have traditionally been used for the management of patients with T2D. These include the sulphonylureas, meglitinides, biguanides, thiazolidinediones and the alpha-glucosidase inhibitors. Several newer classes of agents have also been introduced recently in the pharmacotherapy of T2D, including the incretin mimetics, the dipeptidy peptidase 4 (DPP-4) inhibitors, the sodium glucose co-transporter 2 (SGLT 2) inhibitors and more recently, the dual peroxisome proliferator-activated receptor (PPAR) agonists. Each of these agents has been shown in various experimental and clinical settings to be efficacious in T2D, but each is also associated with a number of adverse effects. Despite the vastarray of drugs introduced, metformin, a biguanide, largely remains the first choice mono therapy in T2D patients but several combination options are also available in poly pharmacy when mono therapy fails to produce the required glycemic control. The increasing number of drugs, together with numerous combination options in poly pharmacy, presents with the clinician an increasing complexity of therapeutic options. The likely pathogenetic mechanism of diabetes operating in the patient, as well as the mode of action, efficacy and safety of the drugs are some of the major considerations in the choice of any given agent or its combinations. This review therefore focuses on the mode of action, pharmacokinetics, indications, efficacy and adverse effects of the OHA used in T2D.

Bioassay Guided Isolation and Evaluation of the Antidiabetic Principles of Combretum dolichopetalum Root.

Aims: The present study was aimed at investigating the antidiabetic potentials of Combretum dolichopetalum root in alloxan-induced animals with the hope of isolating its antidiabetic principles. Study Design: Sixty four Wistar albino rats of either sexes were randomly segregated into 16 groups (n=4). Also, thirty two albino mice were segregated into 8 groups. These received various doses of the plant sample, vehicle or glibenclamide for the antidiabetic study. Place and Duration of Study: This study was done in the laboratory of the Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka between March and October, 2013. Methodology: The root of C. dolichopetalum was extracted with methanol (ME) and fractionated successively with various solvents (n-hexane, chloroform, ethylacetate, methanol and water) to afford the respective fractions: HF, CF, EF, MF and AF. CF was further fractionated to afford six sub-fractions: C1-C6. Acute toxicity study was done using ME. Antidiabetic activity of various doses (p.o.) of ME (100, 200, 400 and 600 mg/kg body weight), its fractions (200 and 400 mg/kg) and sub-fractions (200 mg/kg), glibenclamide (0.2 mg/kg) and vehicle (control) were investigated in alloxan-induced (i.p.) diabetic animals for 9 h. Phytochemical analysis was also carried on ME and fractions. Results: The extract was considered safe with LD50 greater than 5000 mg/kg. ME (400 mg/kg), CF (400 mg/kg) and C3 (200 mg/kg) produced maximum reduction (36.78%, 72.43% and 83.17% respectively) in fasting blood glucose of animals after 9 h which were significantly (P < .01, P < .001) different from the control and better than glibenclamide (48.18%). Phytochemical analysis showed alkaloids, flavonoids, terpens and steroids as the likely antidiabetic agent(s). Conclusion: The root of C. dolichopetalum possesses potent antidiabetic activity which increases as the extract is purified. The antidiabetic effect of the plant may likely be due to the presence of alkaloids, flavonoids, terpens or steroids.

Natural Products as Potential Sources of Antidiabetic Drugs.

Natural products have played and continue to play an invaluable role in the treatment of various diseases and in drug discovery processes. It has remained a source of new compounds with diversified structural arrangements possessing interesting biological activities for various disease treatments. Drugs from natural products are usually considered to be safer, cheaper, easily available and sometimes more efficacious than purely synthetic ones. In recent years, scientists have been in search for safer and more potent drugs from natural sources particularly from medicinal plants. Diabetes is one of the chronic disorders which are associated with high mortality risk. The existing drugs have been identified with one or more adverse effects. In the present review, literature was surveyed to highlight the merits of natural products with regard to their role in diabetic management. Notwithstanding the seemingly decline in the natural product approach to drug discovery in favor of modern approaches such as combinatorial chemistry, literature survey has shown that a lot of research effort is still being directed to natural product in search for new antidiabetic agents. Several antidiabetic phytoconstituents have been isolated from medicinal plants and these were of chemically diversified nature which includes flavonoids, glycosides, terpens, polysaccharides and polypeptides. Based on the merits of nature based medicines, the authors advocate the use of standardized crude forms of some of the natural drugs. Further researches geared towards exploiting the vast array of natural products in our environment and development of the isolated compounds to clinically useful drugs for diabetes management is advocated.