Screening, Diagnosis, and Pharmacotherapy for Type 2 Diabetes Mellitus

Type 2 diabetes is increasing in prevalence. It is pragmatic to screen patients for diagnostic testing. Diet, exercise, and oral therapy remain the primary treatment modalities for type 2 diabetes. First generation sulfonylureas have fallen out of favor due to adverse effects. Second generation sulfonylureas, metformin, or their combinations are recommended first-line. Glipizide and glimepiride are preferred in elderly, hepatically, and renally impaired patients. Metformin is not recommended with chronic heart failure, renal insufficiency, and in the elderly due to lactic acidosis risks. Glitazones are for second-line therapy, should be used cautiously with cardiac insufficiencies, and require routine monitoring of liver enzymes. Meglitinides, not first-line, may offer an alternative to sulfonylureas. Alpha-glucosidase inhibitors, most effective with impaired glucose tolerance, may be combined with sulfonylureas or metformin. Pharmacists play an integral role in management and pharmacotherapy services in diabetes may be implemented in collaborative drug therapy monitoring for maximizing cost effectiveness.

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Toxicity of Oral Agents Used to Treat Diabetes

Journal of Pharmacy Practice ◽

10.1177/0897190005277239 ◽

2005 ◽

Vol 18 (3) ◽

pp. 145-156 ◽

Cited By ~ 1

Author(s):

Pamela Lada ◽

Umbreen Idrees

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lactic Acidosis ◽

Adverse Effects ◽

The Other ◽

Treatment Modalities ◽

Glucosidase Inhibitors ◽

Oral Agents

Oral agents used for the management of type 2 diabetes mellitus include sulfonylureas, biguanides, thiazolidinediones, metglitinides, and/or α -glucosidase inhibitors. These medication classes can be further classified as hypoglycemic and antihyperglycemic agents. Hypoglycemia is a major symptom of toxicity of these agents, particularly with the sulfonylureas, including combination medications that include sulfonylureas. In overdose situations, metformin, a biguanide, can lead to considerable gastrointestinal adverse effects and potentially lactic acidosis in severe cases. Data on the management of toxicities of the other classes are limited. This article will review the treatment modalities that have been used for treating symptomatic hypoglycemia and metformin-induced lactic acidosis.

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Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update

Current Pharmaceutical Design ◽

10.2174/1381612825666190717104547 ◽

2019 ◽

Vol 25 (23) ◽

pp. 2510-2525 ◽

Cited By ~ 5

Author(s):

Bashir Usman ◽

Neha Sharma ◽

Saurabh Satija ◽

Meenu Mehta ◽

Manish Vyas ◽

...

Keyword(s):

Type 2 Diabetes ◽

Patient Compliance ◽

Postprandial Hyperglycemia ◽

Diabetic Patients ◽

Poor Patient ◽

Glucosidase Inhibitors ◽

Poor Patient Compliance ◽

Recent Developments ◽

Alpha Glucosidase

The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety. Alphaglucosidase is a family of enzyme originated from the pancreas which plays a role in the anabolism of 80-90% of carbohydrate consumed into glucose. This glucose is absorbed into the blood and results in frank postprandial hyperglycemia and worsens the conditions of diabetic patients which precipitate complications. Inhibition of these enzymes helps to prevent postprandial hyperglycemia and the formation of glycated end products. Alphaglucosidase inhibitors are reported to be more important in adequate control of type 2, but marketed drugs have various side effects, such as poor patient compliance and also expensive. This proves the needs for other class of drugs with better efficacy, safety, patient compliance and economic. In this review, we have emphasized the recent advances in the field of new alpha-glucosidase inhibitors with improved safety and pharmacological profile.

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Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

Medicinal Chemistry ◽

10.2174/1573406416666200826101205 ◽

2020 ◽

Vol 16 ◽

Author(s):

Marjan Mollazadeh ◽

Maryam Mohammadi-Khanaposhtani ◽

Yousef Valizadeh ◽

Afsaneh Zonouzi ◽

Mohammad Ali Faramarzi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kinetic Study ◽

Active Site ◽

Docking Study ◽

Secondary Amines ◽

Molecular Docking Study ◽

Glucosidase Inhibitors ◽

Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

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Aim to normalize glucose levels and reduce cardiovascular mortality when managing type 2 diabetes in the elderly

Drugs & Therapy Perspectives ◽

10.1007/s40267-019-00619-7 ◽

2019 ◽

Vol 35 (6) ◽

pp. 271-277

Author(s):

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Mortality ◽

The Elderly ◽

Glucose Levels

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A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽

10.3390/nu13010183 ◽

2021 ◽

Vol 13 (1) ◽

pp. 183

Author(s):

Anna Izzo ◽

Elena Massimino ◽

Gabriele Riccardi ◽

Giuseppe Della Pepa

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Elderly Population ◽

The Elderly ◽

Narrative Review ◽

Macrovascular Complications ◽

Diabetic Patients ◽

Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

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Design, Synthesis, and Molecular Docking of Novel Hybrids of Coumarin-Dithiocarbamate Alpha-Glucosidase Inhibitors Targeting Type 2 Diabetes Mellitus

Polycyclic Aromatic Compounds ◽

10.1080/10406638.2021.1887295 ◽

2021 ◽

pp. 1-11

Author(s):

Emad Elahabaadi ◽

Amir Ahmad Salarian ◽

Ehsan Nassireslami

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Molecular Docking ◽

Design Synthesis ◽

Glucosidase Inhibitors ◽

Alpha Glucosidase

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Current Perspectives on Management of Type 2 Diabetes in Youth

Children ◽

10.3390/children8010037 ◽

2021 ◽

Vol 8 (1) ◽

pp. 37

Author(s):

Sachi Singhal ◽

Seema Kumar

Keyword(s):

Type 2 Diabetes ◽

Severe Obesity ◽

Rapid Development ◽

Adult Onset ◽

Socioeconomically Disadvantaged ◽

Lifestyle Modifications ◽

First Line ◽

Diabetes In Youth ◽

First Line Treatment

The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents is on the rise, and the increase in prevalence of this disorder parallels the modern epidemic of childhood obesity worldwide. T2DM affects primarily post-pubertal adolescents from ethnic/racial minorities and those from socioeconomically disadvantaged backgrounds. Youth with T2DM often have additional cardiovascular risk factors at diagnosis. T2DM in youth is more progressive in comparison to adult onset T2DM and shows lower rates of response to pharmacotherapy and more rapid development of diabetes-related complications. Lifestyle modifications and metformin are recommended as the first-line treatment for youth with T2DM in the absence of significant hyperglycemia. Assessment of pancreatic autoimmunity is recommended in all youth who appear to have T2DM. Pharmacotherapeutic options for youth with T2DM are limited at this time. Liraglutide, a GLP-1 agonist, was recently approved for T2DM in adolescents 10 years of age and older. Several clinical trials are currently underway with youth with T2DM with medications that are approved for T2DM in adults. Bariatric surgery is associated with excellent rates of remission of T2DM in adolescents with severe obesity and should be considered in selected adolescents.

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