DM Drugs

Question 1

Insulin (various types)

Answer 1

• Bolus Insulin (covers elevations in glucose after meal OR when need correction; inject b/f eating)
  1- Rapid Acting (onset w/in 15 min; out of system in ~4 hrs) - lispro, aspart, glulisine OR inhaled technophere insulin
  2- Short Acting (30 min onset; 8 hrs)- regular insulin (human)
• Basal Insulin (prevent unchecked gluconeogenesis and ketogenesis b/n meals)
  1- Intermediate Acting (peaks at 6 hrs then out at 14-16 hrs) - NPH (human)
  2- Long Acting - detemir (2x daily), glargine/degludec (longest - once daily)

Question 2

Metformin

Answer 2

• First line drug of choice
• MAO: inhibits gluconeogenesis, improves glucose uptake in liver and muscle, inhibits lipolysis, improves GLP-1 function, inhibits dipeptidyl peptidase IV which degrades GKP-1 and activates AMP-act protein kinase in hepatocytes
• Absorbed in SI –> conc in enterocytes and hepatocytes –> circulates unbound and renally excreted
• Higher glucose = higher effect and lower glucose = lower effect; so less chance of hypoglycemia
• Side Effects - wt loss, lactic acidosis if renal insufficiency, GI, metallic taste, dec B12
• Contraindications - severe liver disease, heavy alcohol use, unstable/acute heart fail

Question 3

sitagliptin, saxagliptin, alogliptin, linagliptin

Answer 3

DPP4 INHIBITORS

• MAO: inhibits DPP4 ability to degrade GLP1 allowing GLP1 to inc insulin and dec glucagon for longer duration (so mainly dec postprandial glucose)
• Adv - very rare side effects and no inc hypoglycemia, wt neutral
• Side Effects - headache, arthralgias, inc LFTs, inc URIs and UTIs, rare hypersensitivity rxn

Question 4

exenatide, liraglutide, albiglutide, dulaglutide

Answer 4

GLP1 AGONISTS

• MAO: mimic endogenous GLP1 so inc insulin secretion, dec glucagon secretion, dec appetite and slow gastric emptying
• Adv - only agent to improve first phase of insulin release after meal
• Disadv - expensive
• Side Effects - transient nausea, wt loss, hypoglycemia in combo w/ insulin or secretogogues, rarely pancreatitis and acute renal failure
• Contraindications - family hx medullary carcinoma or MEN-2 b/c maybe C cell hyperplasia; hx pancreatitis or pancreatic cancer

Question 5

Secretagogues

Answer 5

1 - Sulfonylureas (long-acting - glipizie, glyburide, glimepiride)

• MAO: binds sulfonylurea receptor which closes K+ channels –> opens Ca++ channels –> inc insulin secretion at beta cells which promotes delivery to portal system; liver sees more insulin
• Adv - high efficacy, inexpensive, insulin from actual beta cells so goes into portal circulation so liver sees it
• Side Effects - Wt gain, hypoglycemia (esp long-acting), blood dyscrasias, skin rash

2- Meglitinides (repaglinide, nateglinide)

• Taken immediately b/f meal so multiple times a day (lower compliance)

Question 6

dapagliflozin, canagliflozin, empagliflozin

Answer 6

SGLT2 INHIBITORS

• MAO: inhibit SGLT2 on proximal tubules (normally 90% glucose reabsorption) so inc renal excretion of glucose
• Adv - independent of insulin, wt loss and dec BP, dec cardiovascular complications esp w/ empagliflozin (so most commonly used)
• Disadv - hypotension, dehydration, vol depletion (warn pt to drink water), enhance glucagon b/c lose glucose in urine
• Side Effects - polyuria, inc thirst, dec volume, inc risk vaginal Candida and other genital infections, inc risk UTI, inc LDL cholesterol, inc risk DKA and bone loss/fractures and amputation risk (canagliflozin)
• Contraindications - Type 1 DM, if low eGFR (+ BPH) or if Type 2 prone to ketosis

Question 7

Acarbose/Miglitol

Answer 7

• MAO: inhibit intestinal α-glucosidases which breakdown complex polysaccharides which slows release of glucose in digestion so no post-prandial peak; dec insulin demand
• Side Effects - flatulence, diarrhea
• Adv - safe and some wt loss
• Disadv - only effective if high carb diet and poor compliance b/c GI effects

Question 8

Thiazolidinediones (TZDs)

Answer 8

• Pioglitazone/Rosiglitazone
• MAO: bind to nuclear receptors called peroxisome proliferator activated receptors (PPAR-γ) that amplify intracellular response to insulin –> inc insulin-mediated glucose uptake in skeletal muscle/adipose tissue & enhancement of insulin-mediated suppression of hepatic glucose production
  
  • “Insulin sensitizing agents”
• Side Effects - wt gain, fluid retention, edema, dilutional anemia, precipitates CHF, hepatotoxic, dec bone density (not widely used b/c of effects)
• Adv - inc HDL and dec TGs (Pioglitazone), no renal contraindications, inc effect of other DM drug classes
• Disadv - delayed onset of action (3-8 wks)
• Contraindicated if liver disease or CHF

Question 9

Pramlintide

Answer 9

• MAO: mimics amylin –> slow gastric emptying, dec glucagon secretion and central appetite suppression
• *Amylin is normally co-secreted w/ insulin and has similar effects
• Adv - modest wt loss and satiety
• Disadv- expensive, requires additional injection
• Side Effects - nausea, hypoglycemia (post-meal if do not adjust insulin)

Question 10

Specific Goals of Tx

Answer 10

• Pre-prandial glucose: 80-130
• Post-prandial glucose: < 180
• A1C: < 7%