Glycaemic control in type 2 diabetes: Targets and new therapies

Tahrani, Abd A; Piya, Milan K.; Kennedy, Amy; Barnett, Anthony

doi:10.1016/j.pharmthera.2009.11.001

Cited by 169 publications

(126 citation statements)

References 279 publications

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“…Ademais, a florizina (30) apresenta propriedades farmacocinéticas inapropriadas, dada a labilidade metabólica da ligação O-glicosídica, rapidamente hidrolisada pelas glicosidases, resultando em baixa biodisponibilidade oral e reduzido tempo de meia-vida, além de efeitos tóxicos associados à liberação da dihidrochalcona floretina (31). 35,42,43 A primeira geração de análogos estruturais otimizados da florizina (30) (36) foi o primeiro inibidor seletivo de SGLT-2 a ser aprovado pelo FDA para uso terapêutico, o que ocorreu no ano de 2013. 10,35 Esta nova classe de fármacos tem se demonstrado bem tolerada, segura e eficaz no controle da glicemia em diabéticos, além de minimizar significativamente os danos microvasculares associados à hiperglicemia crônica.…”

Section: Inibidores Do Cotransportador Sódio-glicose 2 (Sglt-2)unclassified

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

2017

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ResumoO diabetes mellitus consiste em uma síndrome metabólica caracterizada por níveis elevados de glicose sanguínea (hiperglicemia). Atualmente, cerca de 90-95% dos casos de diabetes são do tipo II, o qual se desenvolve a partir de um quadro inicial de resistência periférica à insulina. Em decorrência do avanço exponencial dos principais fatores de risco para o estabelecimento da doença, incluindo a obesidade, maus hábitos alimentares, estilo de vida sedentário e envelhecimento populacional, as estatísticas apontam para a existência de uma epidemia global de diabetes tipo II, com estimativas assustadoras para o futuro. Tratando-se de uma doença crônica sistêmica de progressão lenta, há uma demanda imediata por medicamentos eficazes e com um perfil de segurança adequado ao uso contínuo. Esta revisão detalha a evolução dos fármacos antidiabéticos atualmente disponíveis no mercado farmacêutico, demonstrando os avanços realizados até então e os desafios para o futuro.

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Section: Inibidores Do Cotransportador Sódio-glicose 2 (Sglt-2)unclassified

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

2017

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“…None of the current therapeutics has a significant effect on the progression of this disease. 149 In type 2 diabetic subjects, in whom obesity and insulin resistance are present in more than 80% of cases, the treatment should initially be based on a dramatic lifestyle change. It is addressed primarily to the dietary adequacy, with low-calorie diet and implementation of regular physical activity, 150 although with a tendency to crumble.…”

Section: Introductionmentioning

confidence: 99%

“…158 Patients often present poor blood glucose control despite the associated therapeutic measures. 149,158 The glycemic control of an individual with type 2 diabetes is considered optimum when his or her glucose values are similar the level detected in an individual without diabetes, 159 with respect to the prevention of complications. 144 Therefore, the achievement of optimal levels of glycemic control remains a major challenge in clinical practice; only a small portion of people with diabetes attain the therapeutic goals.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, individuals may present skin reactions, gastrointestinal disorders, hematologic reactions, acute coronary events, visual changes and metabolic diseases, which limits the use of these therapies. [147][148][149]152,158,161 Most antidiabetic medications, including sulfonylurea, thiazolidinediones and insulin, improve glycemic control but do not always correct the associated metabolic disorders and are associated with an increase in body weight (as occurs with insulin treatment) by stimulating the appetite; this phenomenon generates concern. 147,161,162 Sulfonylurea has been shown to accelerate apoptosis in beta cells, which results in a decline of linear functions and a decrease in the mass of the human pancreas.…”

Section: Introductionmentioning

confidence: 99%

“…154 Incretin-based therapies such as GLP-1 receptor agonists administrated subcutaneously and DPP-4 inhibitors (dipeptidyl peptidase-4) administered orally offer a new, more current and interesting approach in the management of type 2 diabetes, and the development of new agents is currently underway. 145,149 The two groups that are presently available have been demonstrated to be safe and effective in reducing blood glucose levels while also promoting a favorable effect on weight reduction and maintenance. 148,151,161,162 Some studies have demonstrated the beneficial effects of these promising drugs on the lipid profile and blood pressure in patients.…”

Section: Introductionmentioning

confidence: 99%

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Organic consequences of ileal transposition in rats with diet-induced obesity

et al. 2011

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INTRODUCTION:The clinical management of metabolic syndrome -especially diabetes mellitus type 2 -is notoriously complex due to the progressive nature of this disease. At present, there is a need for a surgical procedure that is effective for the treatment of diabetes mellitus type 2, even in non-obese individuals. The isolated ileal transposition theory could lead to an effective alternative therapy. This intervention has not yet been performed in humans, and there are no reports of its use in an experimental model of diet-induced metabolic syndrome. OBJECTIVES:The objective of this study is to evaluate the physiological effects of ileal transposition in rats with diet-induced metabolic syndrome. The effects of this procedure on glucose and lipid metabolism will be assessed. METHODS:Forty 12-week-old male rats (albino Rattus norvegicus, Wistar, 2BAW, heterogeneous) will be divided into four groups of 10 animals each: the ileal transposition group (TG) comprising animals on a hypercaloric-hyperlipidic diet; the sham group (SG) containing animals that receive the same diet and undergo the sham surgery; control group 1 (CG1), which will receive a hypercaloric-hyperlipidic diet and will not undergo surgery; and control group 2 (CG2), which will consume standard feed and will not undergo surgery. The surgeries will be performed in 20-week-old animals.Blood samples for laboratory testing will be collected from 12-week-old animals on the day of surgery and after eight postoperative weeks, following determination of the weights of the animals and the administration of anesthesia. The levels of serum glucose, insulin, triglycerides, total cholesterol and fractions, glucagon-like peptide-1, C-peptide and glycated hemoglobin will be assessed in all of the animals. The insulin tolerance test will be performed using PRISMA software, and insulin resistance will be calculated by the HOMA-IR indirect test. On specific days, two 20-week-old rats will be separated and randomly distributed in TG and SG. These animals will be followed until the eighth postoperative week. Subsequently, they will be euthanized, and the retroperitoneal and periepididymal fat deposits will be collected and weighed using a precision scale. In addition, the pancreas, liver and intestinal segments will be sent for pathological and immunohistochemical studies.

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Sensitive and specific LC‐ESI‐MS/MS method for determination of ZYDPLA1, a novel long‐acting dipeptidyl peptidase 4 inhibitor in rat plasma: An application for toxicokinetic study in rats

Giri

Patel

et al. 2017

Biomedical Chromatography

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A rapid and highly specific assay was developed and validated for the estimation of ZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as specificity, matrix effect, precision, accuracy, recovery, stability, etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising: (A) 0.2% ammonia in purified water; (B) 0.1% formic acid in isopropyl alcohol/methanol (1: 1 v/v); and (C) acetonitrile at a flow rate of 1 mL/min on an ACE-5, C18 (4.6 × 50 mm) column with a run time of 5.5 min. The quantitation of ZYDPLA1 was achieved by the summation of four multiple reaction mode transitions (m/z 399.7 → 383.0, 399.7 → 276.10, 399.7 → 153.20 and 399.7 → 127.20), while that of the internal standard was by a single multiple reaction mode transition (m/z 309.10 → 281.00). The lower limit of quantitation achieved was 0.01 μg/mL and the method showed linearity from 0.01 to 25 μg/mL. The intra- and inter-day precision (%CV) of the quality control samples was within 8.81% and accuracy was ±10% of nominal values. This novel method was applied for evaluation of toxicokinetics of ZYDLA1 in rats.

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Glycaemic control in type 2 diabetes: Targets and new therapies

Cited by 169 publications

References 279 publications

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

Organic consequences of ileal transposition in rats with diet-induced obesity

Sensitive and specific LC‐ESI‐MS/MS method for determination of ZYDPLA1, a novel long‐acting dipeptidyl peptidase 4 inhibitor in rat plasma: An application for toxicokinetic study in rats

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