Anti-Diabetic Agents

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Rapid Acting Insulin

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Analogues of regular insulin

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Rapid Acting Insulin

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Can be given immediately before meals

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Rapid Acting Insulin

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Avoids postprandial hypoglycemia dueti short duration of action

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Insulin Lispro

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Inversion of proline in B chain at position 28 with lysine at position 29

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Insulin Aspart

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Substitution of proline at position 28 in B chain with aspartic acid

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Insulin Glulisine

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Substitution of lysine for asparagine at position B3 and glutamic acid for lysine at B29

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Insuline Glulisine

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Causes phosphorylation of insulin receptors substrate 2

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Insulin Glulisine

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Has additional anti-apoptotic activity

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Insulin Glulisine

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Carry the risk of tumorgenecity and increased mitogenic activity

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Short Acting Insulin

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Only one that can be given IV

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Short Acting Insulin

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Useful in management of DKA, after surgery or when there is infection

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Intermediate Acting Insulin

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Dissolves more gradually when administered subcutaneously; longer action

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Long Acting Insulin

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Slow onset and flat peak:basal insulin

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Insulin Glargine

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Analog of NPH insulin

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Insulin Glargine

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pH 4.0 and forms dimer

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Insulin Glargine

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First long acting peakless insulin

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Insulin Glargine

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Less soluble at physiologic pH and more sokubke at acidic pH

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Insulin Glargine

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Given once a day

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Insulin Glargine

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Not meant to be mixed with other insulin

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Insulin Glargine

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More painful when injected

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Insulin Glargine

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Less immunogenic than human insulin

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Insulin Detemir

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Threonine removed at B3 and myristic acid is attached at B29

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Insulin Detemir

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Fatty acid moiety binds to albumin proloning action

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Insulin Detemir

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Soluble basal insulin analogue at neutral pH

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Insulin Detemir

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12 hours duration of action given twice daily

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Insulin Detemir

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Causes weight reduction due to direct effect on hypothalamus

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Insulin Detemir

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Less risk for inducing tumor due to less potent binding with IGF-1R

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Insulin Degludec

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New basal insulin forming soluble multihexamer

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Insulin Degludec

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Ultra long acting with >24 hours duration of action

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Insulin Degludec

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Effective at physiologic pH

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Sulfonylurea

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1st oral anti-diabetic agent developed

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Sulfonylurea

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Limit gluconeogenesis in the liver

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Sulfonylurea

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Decrease breakdown of lipids to fatty acids

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Sulfonylurea

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Reduce clearance of insulin in the liver

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Sulfonylurea

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Second line treatment for Type 2 DM

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Aspirin, Sulfonamides, allopurinol, fibrates

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Prolongs the effect if sulfonylurea

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Beta Blockers

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Reduce hypoglycemia unawareness

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Tolbutamide

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Best administered in divided dose

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Tolbutamide

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Half-life is 4-5 hours

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Phenylbutazone, Azole, Sulfisoxazole

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Inhibit liver metabolism of Tolbutamide

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Chlorpropamide

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Half-life is 32 hours

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Chlorpropramide

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Flushing when ingested with alcohol and hyponatremia

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Tolazamide

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Half-life is 7 hours

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Acetohexamide

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Active metabolites have longer half lives

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Glyburide

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Contraindicated with hepatic impairment and renal insufficiency

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Glipizide

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Should be taken 3 minutes before breakfast

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Glimepiride

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Most potent sulfonylurea

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Gliclazide

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Half-life is 10 hours with inactive metabolites

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Meglitinide

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Use with caution in hepatic insufficiency but can be used in renal insufficiency

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Meglitinide

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Rapid absorption within 20 minutes

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Metformin

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Main first line drug for Type 2 DM

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Metformin

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Activates adenosine monophosphate-activated protein kinase

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Metformin

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Cause hepatic uptake of glucose and inhibits gluconeogenesis

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Metformin

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Highly tolerated, very mild side effects

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Metformin

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Low risk of hypoglycemia

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Metformin

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Low chance of weight gain

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Metformin

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Delay progression of Type 2 DM

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Metformin

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Improves insulin sensitivity by activating insulin receptor expression

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Metformin

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Enhance tyrosine kinase activity

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Metformin

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Lowers plasma lipid levels through PPAR

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Metformin

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Reduces food intake by GLP-1 mediated incretin actions

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Metformin

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GI disturbances, lactic acidosis, Vit. B12 and folic acid deficiency

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Thiazolidinedione

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Improve insulin action

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Thiazolidinedione

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Agonist of PPAR and facilitate increased glucose uptake

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Thiazolidinedione

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Reduces fatty acid accumulation

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Thiazolidinedione

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Reduces inflammatory cytokines

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Thiazolidinedione

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Increased adiponectin levels

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Thiazolidinedione

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Preserves beta cell integrity and function

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Thiazolidinedione

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Water retention

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Alpha Glucosidase Inhibitor

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Inhibit enzyme delaying carbohydrate absorption

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Alpha Glucosidase Inhibitor

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Structurally similar to oligosaccharides

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Alpha Glucosidase Inhibitor

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Reversible, competitive inhibitors of oligosaccharide digestion

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Acarbose

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Pseudo-tetrasaccharide compound

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Acarbose

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Most common side effects are GIT symptoms

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Alpha Glucosidase Inhibitor

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Does not cause hypoglycemia

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GLP 1 Agonist

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Highly resistant to degradation by DPP4

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Exenatide

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Homologye to native GLP 1

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Liraglutide

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GLP-1 analog sharin 97% sequence identity

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Liraglutide

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Long duration of action (24 hours)

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Liraglutide

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Lowers HbA1C by 1.5%

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DPP4 Inhibitors

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Inhibit degradation of incretin

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DPP4 Inhibitor

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Impact postprandial lipid levels

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DPP4 Inhibitors

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Nasopharyngitis, URTI headache

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SGLT2 Inhibitors

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Insulin-independent glucose lowering

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SGLT2 Inhibitor

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Inhibit glucose reabsorption in the proximal renal tubule

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SGLT2 Inhibitor

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Effective in advanced stages of Type 2 DM when pancreatic Beta cells are lost

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SGLT2 Inhibitors

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Provide modest weight loss and blood pressure reduction

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Pramlintide

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Amylin analog

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Pramlintide

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Delays gastric emptying

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Pramlintide

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Suppress pancreatic secretion of glucagon

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Pramlintide

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Enhances satiety

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Pramlintide

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FDA-approved therapy for Type 1 and Type 2 DM

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Bromocriptine

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Dopamkne 2 receptor agonist

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Bromocriptine

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Induction in insulin sensitivity and glucose metabolism