Anti-diabetic medications

This is a short video on medications used to treat diabetes mellitus by lowering blood glucose levels I created this presentation with Google Slides. Image were created or taken from Wikimedia Commons I created this video with the YouTube Video Editor. ADDITIONAL TAGS: Insulin Bind insulin receptor, activate tyrosine kinase receptor pathway All used for DM1, DM2, GDM Rapid acting insulin: Lispro, Aspart, Glulisine Monomeric insulin analogs → monomers in solution Peak time in 1 hour → no LAG Used for post-prandial glucose control Short acting insulin: regular insulin Same insulin found in human body → dimer/hexamer in sol’n Peak in 2 to 4 hours Administered IV for DKA Intermediate acting insulin: NPH Peak in 4 to 10 hours Long acting insulin: glargine, detemir Insulin analog → precipitates at body pH Doesn’t really peak, relatively flat Good for mimicking basal insulin secretion Biguanides METFORMIN Sensitizes to insulin Thought to stimulate liver enzyme AMPK → exact MoA unclear Does not require functioning beta cells More effective in liver than muscle Administered orally Decreases HbA1c by 1-2% Mild weight loss SEs: diarrhea, nausea, vit B12 deficiency, lactic acidosis Contraindicated in kidney/liver/heart failure First line for DM2 Insulin Thiazolidinediones TZDs or -glitazones: pioglitazone and rosiglitazone Sensitizes to insulin → increases number and sensitivity Bind to peroxisome proliferator-activated receptor gamma (PPARγ) More effective in periphery (muscle/fat) than liver Does not require functional beta cells Administered orally Decreases HbA1c by 1-1.5% Mild weight gain, increases LDL, expensive, slow onset SEs: weight gain, edema, heart failure, liver toxicity, fractures Safe with renal failure Increases secretion of insulin Decreases HbA1c by 1-2% SEs: weight gain, hypoglycemia, allergies (sulfa drugs) Administered orally Sulfonylureas: tolbutamide, chlorpropamide, glipizide, glyburide, glimepiride Binds to SU on the ATP-activated potassium of beta cells → requires functional beta cells Blocks K channel → Ca influx → activate insulin release Meglitinides: repaglinide, nateglinide Bind to another receptor to block K channel → Ca influx → activate insulin release Faster onset, slower duration, more expensive than sulfonylureas Anti alpha glucosidase Acarbose, miglitol Slows absorption of carbohydrates in the proximal gut Alpha glucosidase is an enzyme that hydrolyzes carbs in the brush border of the GI tract Delays carb breakdown and thus absorption Decreases postprandial hyperglycemia Administered orally Decreases HbA1c by 0.5-1% SEs: flatulence (causes poor adherence), other GI disturbance, liver enzyme elevation Expensive Incretin mimetics Incretins GLP-1 and GIP are gut-derived hormones that: (1) stimulate insulin secretion, (2) inhibit glucagon secretion, (3) slow gastric emptying, and (4) promote satiety Incretin release stimulated by eating GLP-1 receptor analogs: exenatide, liraglutide, dulaglutide Mimick GLP-1 and produce same incretin effects Cause weight loss Dipeptidyl peptidase-4 (DPP4) is the enzyme that breaks down incretins DPP4 inhibitors increase blood conc of incretins -agliptins: sitagliptin, saxagliptin, linagliptin Administered orally Amylin analogues Synthetic amylin analogue: pramlintide Co-secreted with insulin, deficient in diabetes, and has the following effects: (1) inhibit glucagon secretion, (2) slow gastric emptying, (3) promote satiety Decreases HbA1c by 0.5-1% SEs: nausea, hypoglycemia Promotes moderate weight loss Administered orally or subcutaneously Cause weight loss Glycosurics Promote renal excretion of glucose Sodium-glucose cotransporter 2 (SGLT2) is a channel in the proximal tubule responsible for 90% of glucose reabsorption SGLT2 inhibitors: canagliflozin, dapagliflozin, empagliflozin Decreases HbA1c by 0.5-1% SEs: UTIs, vuvlvovaginal candidiasis (vaginal yeast infxns), glycosurea, renal failure, decrease blood pressure, hyperkalemia, dehydration Promotes substantial weight loss Colesevelam Bile acid sequestrant → exact MoA unknown Decreases HbA1c by 0.3-0.4% SEs: constipation, dyspepsia, nausea, hypertriglyceridemia Bromocriptine Dopamine agonist → exact MoA unknown Decreases HbA1c by 0.4-0.5% SEs: headache, dizziness, nausea, vomiting