Melissa preg Flashcards
Describe the MOA of metformin in the treatment of T2D
The exact mechanism of metformin is not fully understood. However it does result in increased activity of AMPK in hepatocytes. AMPK works to cause downstream increase in the activity of processes that produce ATP, and decrease those that use up ATP. It affects glucose metabolism in various ways including increased glucose uptake into skeletal muscle, reduced gluconeogenesis, reduced glucose absorption from GI and reduced lipolysis. This therefore reduces levels of glycaemia.
Explain how metformin can cause lactic acidosis
Metformin can cause lactic acidosis by inhibiting pyruvate dehydrogenase needed to convert pyruvate to acetyl Co A for entry into krebs cycle. Pyruvate is therefore shunted down the anaerobic pathway to produce lactate which begins to accumulate. In patient’s with renal impairment, the lactic acid cannot be effectively excreted which causes a further rise in lactic levels.
Describe the mOA of DPP-4 inhibitors
“Gliptins” - Linagliptin, Saxagliptin
DPP-4 inhibitors prevent the premature breakdown of incretins GLP-1 and GIP, prolonging their activity. This leads to increased insulin secretion from pancreatic beta cells in a glucose-dependent manner. Additionally, GLP-1 suppresses glucagon release from alpha cells, reducing hepatic glucose production. These combined effects contribute to improved glycemic control.
