Phenformin has been banned from India since 2003
Mechanism of action
• Increase uptake and utilization of glucose by skeletal muscle, which reduces insulin resistance
• Inhibit hepatic gluconeogenesis
• Retard intestinal absorption of glucose
• Promote insulin binding to its receptor
• Reduce plasma glucagon level
Advantages:
• Besides lowering blood glucose levels, it also lowers LDL, VLDL and elevates HDL
Adverse effects
Lactic acidosis, vitamin B12 deficiency, anorexia, nausea, flatulence and diarrhea30
INSULIN SECRETOGOGUES - SULFONYL UREAS
• First generation o Tolbutamide o Chlorpropamide o Tolazamide
• Second generation o Glimepiride o Glipizide o Glyburide o Gliclazide
Mechanism of action They act on sulfonyl urea receptor…show more content… Mechanism of action
Acts on peroxisome proliferation activating receptor γ (PPAR – γ) receptors. These are nuclear hormone receptors involved in glucose and lipid metabolism, mainly expressed in adipose tissue and to a lesser extend on cardiac, skeletal, and smooth muscle cells, islet β cells, vascular endothelial cells and macrophages. Ligands which occur endogenously are oxidized linoleic acid, arachidonic acid and the prostaglandin metabolite. Pioglitazone is a synthetic ligand for PPAR – γ receptors. Activation causes heterodimerisation with retinoid X receptor and causes interactions of co-repressors & co-activators leading to adipocyte differentiation, promotes uptake of circulating fatty acids into fat cells and shifts of lipid stores from extra-adipose to adipose tissue. It also increases the tissue sensitivity to insulin. It increases insulin mediated glucose uptake by 30-50% in type 2 diabetes mellitus patients. Also increases insulin mediated disposal of glucose in skeletal muscles and indirect effects mediated by secreted products of adipose tissue (adiponectin). Also reduces hepatic glucose production & hepatic glucose…show more content… These agents cause a reduction of postprandial hyperglycemia by inhibition of the enzyme α- glucosidase.
Adverse effects
Malabsorption, flatulence, diarrhea & bloating. Elevation of hepatic transaminases, cutaneous hypersensitivity are rare adverse effects35.
GLP-1 RECEPTOR AGONISTS
EXANETIDE & LIRAGLUTIDE
Exendin 4 is a naturally occurring reptilian peptide homologous to GLP-1 which is not metabolized by DPP-4 and has a plasma t1/2- 2-3 hours
Exanetide is a synthetic exendin-4. Liraglutide is nearly identical to GLP-1. They have additional effect of reduction of body weight36.
Mechanism of action
GLP-1 receptors are expressed by β cells of the pancreas, cells in the CNS, peripheral nervous system, heart, kidney, lung, GI mucosa. Activation of GLP-1 receptors causes results in alteration of several ion channels via Camp-PKA, PKC, PI3K pathways and by many guanine nucleotide exchange factors (GEFs) resulting in increased insulin biosynthesis and exocytosis in a glucose dependant manner37.
Adverse