Department Of Human Genetics And Molecular Medicine

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Author: search.filters.author.Munshi, AnjanaSubject: search.filters.subject.Pharmacokinetics

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    Pharmacogenomics of GLP-1 receptor agonists: Focus on pharmacological profile
    (Elsevier B.V., 2022-10-28T00:00:00) Jakhar, Kalpna; Vaishnavi, Swetha; Kaur, Prabhsimran; Singh, Paramdeep; Munshi, Anjana
    Type 2 Diabetes mellitus (T2DM) is a multifactorial metabolic disorder also known as a silent killer disease. Macrovascular and microvascular complications associated with diabetes worsen the condition leading to higher comorbidity and mortality rate. Currently, available treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4 (dipeptidyl-peptidase-4) inhibitors, SGLT-2 inhibitors, and Glucagon Like Peptide-1 receptor agonists (GLP-1RAs). Synthetic agonists of GLP-1 hormone, GLP-1RAs are an emerging class of anti-diabetic drugs which target the pathophysiology of diabetes through various mechanisms and at multiple sites. They promote insulin secretion from beta cells, and the proliferation of beta cells inhibits glucagon secretion, delays gastric emptying and induces satiety. However, treatment is reported to be associated with inter-individual variations and adverse drug reactions, which are also influenced by genetic variations. There have been a few pharmacogenetic studies have been carried out on this drug class. This review discusses all the available GLP-1RAs, their pharmacokinetics, pharmacodynamics and genetic variation affecting the inter-individual variation. � 2022 Elsevier B.V.
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    �The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics�
    (Elsevier B.V., 2021-05-11T00:00:00) Kaur, Prabhsimran; Behera, Bidwan Sekhar; Singh, Sandeep; Munshi, Anjana
    Diabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dipeptidyl peptidase-4) and GLP-1 (glucagon-like peptide) analogs. However, many side effects contributing to the devastation of the disease are associated with them. Sodium glucose co-transporter-2 (SGLT2) inhibition has been reported to be new insulin-independent approach to diabetes therapy. It blocks glucose uptake in the kidneys by inhibiting SGLT2 transporters, thereby promoting glycosuria. Dapagliflozin, empagliflozin and canagliflozin are the most widely used SGLT2 inhibitors. They are effective in controlling blood glucose and HbA1c levels with few side effects including hypoglycemia or weight gain which makes them preferable to other anti-diabetic drugs. However, treatment is found to be associated with inter-individual drug response to SGLT2 inhibitors and adverse drug reactions which are also affected by genetic variations. There have been very few pharmacogenetics trials of these drugs. This review discusses the various SGLT2 inhibitors, their pharmacokinetics, pharmacodynamics and genetic variation influencing the inter-individual drug response. � 2021 Elsevier B.V.