Medications

• Insulin Products

  
  

  • Rapid Acting
  • Short Acting
  • Intermediate Acting
  • Long Acting
  • Pre-mixed insulins
• Pre-mixed insulins

  • Insulin aspart and insulin aspart protamine aka Novolog Mix / Novolog 70/30
  • Insulin lispro and insulin lispro protamine
  • Insulin isophane and insulin regular
• Combination injectables - insulin and noninsulin

  • Insulin glargine plus lixisenatide
  • Insulin degludec plus liraglutide
• Insulin Secretagogues


  ORAL

  • Sulfonylureas - glimepiride, glipizide, glyburide
  • Meglitinides - repaglinide, nateglinide
• Insulin Sensitizers


  ORAL

  • Biguanide - Metformin
  • Thiazolidinediones - Pioglitazone, Rosiglitazone
  • Alpha-glucosidase inhibitors - Acarbose, Miglitol
  • SGLT-2 inhibitors - Canagliflozin aka invokana, Empagliflozin aka jardiance, dapagliflozin aka farxiga, ertugliflozin, bexagliflozin
• Incretin Mimetics


  Oral and Parenteral

  • DPP-4 inhibitors (oral) - Sitagliptin aka Januvia, Saxagliptin, Linagliptin, Alogliptin
  • GLP-1 agonists (parenteral) - exenatide, liraglutide aka victoza / saxenda, lixisenatide, dulaglutide aka trulicity, semaglutide aka ozempic/rybelsus (both oral and parenteral)
• Amylin analog

  PARENTERAL

  • Pramlinitide
• Medications shown to reduce cardiovascular risk


  Canagliflozin aka Invokana, Dapagliflozin aka farxiga, Empagliflozin aka Jardiance, Liraglutide aka victoza / saxenda, Dulaglutide aka trulicty, Semaglutide aka ozempic/rybelsus
• Medications indicated for CKD


  Dapagliflozin aka farxiga, Empagliflozin aka jardiance
• Medications indicated for HF and.or reduction of HF hospitalization


  Dapagliflozin aka Farxiga, Empagliflozin aka Jardiance, Canagliflozin aka Invokana
• Medications indicated for obesity and/or weight management


  Liraglutide aka victoza / saxenda, Semaglutide aka ozempic / rybelsus, Tirzepatide
• Insulin product MOA


  2 main ones

  • Promotes uptake of glucose by skeletal muscle/adipose tissue by binding to insulin receptors leading to translocation and activation of GLUT4 and effects on lipid metabolism, cell growth and division and protein synthesis
  • Reduces glucose output by the liver by stimualting enzymes involved in glycogen synthesis (enhances storage) and inhibits enzymes involved in glycogenolysis and gluconeonesis
• Insulin products facts

  • Adverse effects: hypoglycemia = HA, tachycardia, vertigo, anxiety, confusion, diaphoresis; weight gain, lipodystrophy, local injection site reactions, allergic reactions, hypersensitivty
  • Contraindications: CANNOT be administered orally b/c GI tract degrades polypeptide structure
  • Counseling: remind patient to rotate injection sites and provide education on proper storage
• Administer rapid acting insulin around meals
• Administer short acting insulin 30-60 minutes before meals
• U-500 BBW and clinical use


  • U-500 requires extreme caution d/t association w/ high risk of hypoglycemia that can be life-threatening if dose/admin is incorrect
  • Useful for tx of insulin-resistant patients with diabetes requiring daily doses > 200 units
• Sulfonylureas: Glimepiride, Glipizide, Glyburide 


  • MOA: increase secretion of insulin from functioning pancreatic beta cells by binding to sulfonylurea receptor on beta cell, leading to closure of ATP-dependent potassium channels, depolarization of the cell membrane, and opening of Ca2+ channels and this increase in intracellular Ca 2+ leads to increased insulin secretion
  • AE: hypoglycemia, weight gain, rash, photosensitivity, dyspepsia, headache
  • CI: DKA, T1DM, hypoglycemic awareness, hypersensitivity, severe liver or kidney disease
• Sulfonylureas clinical info

  Lowers A1C by 1-2%, reduces both fasting and postprandial BG, some pts have "secondary failure" i.e efficacy of meds decline

  • Glimepiride: once daily, take w/ breakfast or first meal of day
  • Glipizide: once or twice daily, if >15 mg should be twice, regular (30 min before meal) or extended (take w/ meal) release; preferred in RENAL insufficiency
  • Glycuride: once or twice, >10 mg should be twice, take w/ bfast or first meal, re-titrate between versions, AVOID in elderly and renal insufficiency
• Meglitinides: Repaglinide, Nateglinide

  • MOA: similar to sulfonylureas but bind to a different receptor site, have FASTER onset of action and shorter duration of action than sulfonylureas
  • AE: hypoglycemia, weight gain (less than sulfonylureas)
  • CI: DKA, T1DM, hypoglycemic unawareness
  • Interactions: CYP3A4 inhibitors/induces, NO Repaglinide w/ Gemfibrozil
  • PtC: Administer 3 times daily, 1-30 mins before meal, if skip meal → SKIP dose
  • Clinical use: Lower A1c by 0.5-1 % (1.5-1.8 when combo w/ metformin), reduce postprandial BG
• Biguanide: Metformin


  • MOA: primarily inhibits hepatic gluconeogenesis, improves peripheral glucose uptake/utilization to decrease peripheral insulin resistance and may decrease/slow intestinal absorption
  • AE: n/v/d (high incidence early so take w/ food, improve over time), B12 deficiency
  • CI: renal failure or severe impairment (GFR < 30), GFR 30-45 still not recommended, D/C metformin if need IV iodinated contrast media, don’t use in pt w/ increased risk for lactic acidosis (severe hepatic or pulmonary disease, uncontrolled HF)
  • BBW: Rare, lactic acidosis
• Metformin clinical info

  • PtC: 1st line for T2DM, improves micro/macrovascular outcomes, +/- weight loss, positive effect on lipid profile, does NOT cause hypoglycemia if monotherapy
  • Clinical use: Lower A1C by 1-2 %, reduces fasting BG
  • Monitor: renal function before initiation of therapy and periodically after, Vitamin B12 levels about every 2-3 years or “periodic” testing
• Thiazolidendiones: Pioglitazone, Rosiglitazone


  • MOA: Primarily acts as agonists at peroxisome proliferator-activated-receptor-gamma (PPAR-gamma) located in adipose tissue, skeletal muscle and liver, resulting in an increase in glucose uptake in these tissues leading to increased insulin-sensitivity and decreased insulin resistance
  • Secondary MOA: decreased hepatic gluconeogenesis
• Thiazolidendiones

  • AE: weight gain, edema (m.c. w/ concomitant use of insulin, anti-inflammatory, glucocorticoids, or dihydro CCBs), worsening HF, MI (rosiglitazone), hepatotoxicity (rare), potential cause of bladder cancer (pioglitazone) Hand/Feet bone fractures in postmenopausal women (rare)
  • CI: Hypersensitivity, hx/risk of bladder cancer (pioglitazone), caution in pt w/ hepatic disease
  • BBW: Class III or IV HF, rosiglitazone was part of FDA restricted access but was removed in 2013
  • PtC: may be taken with or without food
  • Clinical use: Lower A1c by 0.4-0.6 %, mostly reduced fasting BG
• Alpha-glucosidase inhibitors: acarbose, miglitol


  • MOA: reduce BG concentrations by decreasing rate of glucose absorption AND delay the digestion of starch and disaccharides by competitively inhibiting the enzyme alpha-glucosidase (located in brush border of intestinal tract that convert oligosaccharides and disaccharides into glucose)
  • AE: Flatulence, abdominal discomfort, diarrhea (80% of pt, may improve after 4-8 weeks of use), Elevation of hepatic enzymes (rare, monitor LFTs every 3 mo for 1st year then periodically)
• Alpha-glucosidase inhibitors

  • CI: hypersensitivity, DKA, IBD, GI obstruction, malabsorption, cirrhosis
  • PtC: Dose 3 times daily w/ first bite of meal, gradually titrate up to target dose, if dose missed but meal completed → SKIP dose and take at next meal
  • Clinical use: Lower A1C by 0.5-1 %, reduce postprandial BG
• SGLT-2 inhibitors (-flozin ending)


  • MOA: inhibits SGLT-2, leading to a reduction in the reabsorption of filtered glucose and thus an increase in glucose excretion
  • AE: Hypotension, hyperkalemia, genital mycotic infections, UTIs, increased urination, weight loss
  • CI: hypersensitivity, pt w/ CrCl < 45 mL or on dialysis
  • BBW: risk of amputation (canagliflozin aka invokana)
• SGLT-2 inhibitors (-flozin ending) clinical info


  • PtC: does not cause hypoglycemia as monotherapy, can lead to weight loss, no generic available so can be expensive, have been found to reduce systolic and diastolic BP by 4-6 mmHg and 1-2 mmHg, respectively
  • Clinical use: Lower A1C by 0.8-1.2 %, reduced both postprandial and fasting BG
  • FDA approved for reduction in the risk of major CV events, Empagliflozin FDA approved for reduction in risk of CV death in adults w/ T2DM and established CV disease
  • Have renoprotective effects
• DPP-4 inhibitors: sitagliptin aka januvia, -liptin ending


  ORAL

  • MOA: inhibit the DPP-4 enzyme from breaking down endogenous GLP-1 and GIP, resulting in glucose-dependent increased insulin secretion by pancreas and decreased glucagon secretion. Additionally results in, increased uptake of glucose from blood by tissues and suppression of appetite
  • AE: rare but pancreatitis and skin reactions possible
  • CI: hx of pancreatitis, DKA, T1DM
• DDP-4 inhibitors clinical information: sitagliptin aka januvia, -liptin ending


  • 
    
  • PtC: oral once daily, dosage adjustment needed in renal insufficiency (except for linagliptin), does not cause hypoglycemia as monotherapy, weight neutral, possible beta-cell sparing effect
  • Clinical use: Lower A1C by 0.6-0.8 %, primarily reduced postprandial BG
• GLP-1 agonists: -tide ending, liraglutide aka victoza/saxena, dulaglutide aka trulicity, semaglutide aka ozempic/rybelsus


  • PARENTERAL
  • MOA: synthetic analogues of human GLP-1 that result in glucose-dependent increased insulin secretion by pancreas and decreased glucagon secretion. Also, reduces gastric emptying and increases satiety
  • AE: n/v/d, injection site nodule, RARE = pancreatitis and kidney dysfunction
• GLP-1 agonists warnings: -tide ending, liraglutide aka victoza/saxena, dulaglutide aka trulicity, semaglutide aka ozempic/rybelsus


  • CI: gastroparesis, hx of pancreatitis, pt w/ multiple endocrine neoplasia syndrome type 2 of family hx of medullary thyroid carcinoma
  • Interactions: may reduce rate and extent of absorption of drugs that require rapid absorption so separate by at least 1 hour
  • BBW: Risk of thyroid C-cell tumor (except semaglutide)
• GLP-1 agonists clinical info: -tide ending, liraglutide aka victoza/saxena, dulaglutide aka trulicity, semaglutide aka ozempic/rybelsus



  • PtC: possible weight loss, beta-cell sparing effect, no generic so expensive, ASCVD benefit with liraglutide most then semaglutide, then exenatide extended release
  • All doses via subcutaneous injection, only semaglutide also oral
  • Twice daily = Exenatide, Once daily = Victoza, Once weekly = Exenatide (Bydureon), Dulaglutide, Semaglutide
  • Clinical use: Lower A1c by 0.6-2.1 %, effect on fasting and postprandial BG varies based on meds
• Amylin analog: Pramlinitide


  PARENTERAL

  • MOA: synthetic analog of human amylin (pancreatic hormone) leading to glucose-dependent inhibition of glucagon secretion, reduced rate of gastric emptying, increased satiety 
  • AE: n/v, hypoglycemia w/ insulin
  • CI: gastroparesis, hypoglycemic unawareness, A1C >9%, pt who will not self-monitor BG
  • May reduce rate and extent of absorption of drugs that require rapid absorption, separate by an hour
• Amylin analog: pramlintide clinical information


  • PtC: may lead to weight loss, administer subcutaneous prior to major meals, SKIP any missed doses and resume at next meal, mealtime insulin dose must be reduced by 50% upon initiation of this med
  • NEVER mix pramlintide in same syringe w/ insulin for administration
  • Clinical use: Lower A1C by 0.5-0.7 %, primarily lowers postprandial BG
  • For tx of T1DM and T2DM as adjunct therapy for pt who use mealtime insulin therapy and have failed to achieve desired glucose control
• What meds lower postprandial BG only

  Amyling analog, DPP-4 inhibitors, alpha glucosidase inhibitors, meglitinides
• What meds lower both fasting and postprandial BG 


  Sulfonylureas, SGLT2 inhibitors, GLP-1 agonist (extent varies)
• What meds lower fasting BG

  TZDs, Biguanide