DM drugs

Question 1

Metformin

(Glucophage)

Answer 1

• first line for T2DM
• -Dosing: 500mg-2000mg/day
• Max CLINICAL dose: 2000mg/day (1000mg PO BID)
• BBW : Lactic Acidosis
• Common ADE: diarrhea (self-limiting), cramping, nausea, taste disorder
• Take with food
• XR should be used in patients that don’t tolerate IR with BID dosing
• D/C prior to iodinated contrast procedures
• potential B12 deficiency

Question 2

Metformin MOA

Answer 2

**suppression of hepatic glucose production

** ↑ insulin-mediated muscle glucose uptake

**↑ intestinal glucose utilization

Question 3

Sulfonylurea (2nd) generation

Answer 3

• Glimepiride (Amaryl)
• Glipizide (Glucotrol, Glucotrol XL)
• Glyburide (Diabeta)

Question 4

Sulfonylurea (2nd) generation

Answer 4

• -Take 30 min prior to meals
• • Test G6PD deficiency for hemolytic anemia
• -Prolong use may result in worsening beta cell function (“beta cell burnout”
• -Not effective in pt with long duration of T2DM
• • Glimepiride (Amaryl)- preferred in liver dysfunction
• • Glipizide (Glucotrol) – preferred in renal insufficiency (short t1/2)
• -Rapid onset of action/shorter durability vs. metformin

Question 5

Sulfonylurea (2nd) generation MoA

Answer 5

** Close 𝐾𝐴𝑇𝑃channels on beta cell plasma membranes

Physiologic action:

**↑ insulin secretion

Question 6

TZD

Answer 6

• Pioglitazone (Actos)
• Rosiglitazone (Avandia)

Question 7

TZD

Answer 7

• -Take with or without food
• -BBW: may cause or worsen heart failure
• -CI in patients with class III/IV HF
• -ADE: fluid retention, peripheral edema, weight gain, risk of bone fracture/atypical fracture
• -Onset: 3 weeks (long onset of action)
• -d/c if signs of hepatitis, AST/ALT > 3x normal
• -Monitor: AST/ALT, visual exam
• -check LFT Q3-6 months
• -Bladder cancer (pioglitazone)
• -↑ LDL cholesterol (rosiglitazone)

Question 8

TZD MoA

Answer 8

• activates the nuclear transcription factor PPAR-y (gamma)
• Physiologic action: ↑ insulin sensitivity

Question 9

DDP-4 inhibitors

Answer 9

• Sitagliptin (Januvia)
• Saxagliptin (Onglyza)
• Linagliptin (Trajenta)
• Alogliptin (Nesina)

Question 10

DDP-4 inhibitors

Answer 10

• • Start sitagliptin at 100mg PO daily (25mg and 50mg are renal dose, no need for titration)
• -Not associated with hypoglycemia or weight gain
• -Monotherapy when metformin is CI or in dual/triple tx
• -ADE: nasopharyngitis, pancreatitis, upper respiratory infection, HA, joint pain
• -Saxagliptin, linagliptin-preferred in severe hepatic failure
• -linagliptin- no renal adjustment required
• -DO not combined with GLP-1 receptor inhibitors

Question 11

DDP-4 inhibitors MOA

Answer 11

• MOA: inhibit DDP-4 activities
• Physiologic action:
  
  • ↑ postprandial incretin (GLIP-1) concentration
  • ↑ insulin secretion and ↓ glucagon secretion (glucose dependent)

Question 12

GLP-1 receptor agonist

Answer 12

• Long acting
  
  • Exenatide extended release (Bydureon), Liraglutide(Victoza), Dulaglutide (Trulicity)
  • Semaglutide (Ozempic)
• Short acting
  
  • Exenatide (Byetta)
  • Lixisenatide (Adlyxin)

Question 13

GLP-1 receptor agonist

Answer 13

• – Take within 60 minutes prior to a meal
• –ADE: Nausea (40-44%) diarrhea, vomiting, constipation (slow gastric emptying)
• -Not recommended in combination with SGLT-2 or bonus insulin
• –GLP-1 decrease FBG, PPBG, weight, and insulin requirement when combined with basal insulin or bonus insulin (not FDA approved, but clinically safe and effective- 2016 ACCP GLP-1 addon to bolus insulin)
• –BBW: thyroid C-cell tumors
• –Precaution: risk of acute pancreatitis

Question 14

GLP-1 receptor agonist MOA

Answer 14

• Activated GLP-1 receptor
• Physiologic action:
  
  • ↑ insulin secretin (glucose dependent)
  • ↓ glucagon secretion (glucose dependent)
  • slow gastric emptying
  • ↑ satiety

Question 15

SGLT-2 inhibitors

Answer 15

• Canagliflozin (Invokana)
• Dapagliflozin (Farxiga)
• Empagliflozin (Jardiance)

Question 16

SGLT-2 inhibitors

Answer 16

• -↓ body weight 1.6-2.8kg, ↓ SBP 3.6- 5.1mm Hg
• -Drink plenty of water to prevent dehydration
• -Difference in efficacy (glycemic control) between empagliflozin 10mg and 25mg is < 1%
• BBW: risk of AMPUTATION (canagliflozin)
• -Risk of bone fractures (canagliflozin)
• • DKA risk (all agents, rare in T2DM)
• • Genitourinary infections
• -Risk of volume depletion, hypotention
• -↑ LDL cholesterol
• CVD benefit: Empagliflozin > canagliflozin (no CVD benefit in dapagliflozin)

Question 17

SGLT-2 inhibitors

Answer 17

• MOA: inhibit SGLT-2 in the proximal nephron
• Primary physiologic actions:
  
  • Blocks glucose reabsorption by the kidney
  • ↑ glucososuria

Question 18

ASCVD benefits

Answer 18

liraglutide > semaglutide > exenatide ER

Question 19

Weight lost:

Answer 19

semaglutide > liraglutide > dulaglutide > exenatide > lixisenatide

Question 20

“ DO NOT USE” combinations

(due to therapy duplications)

Answer 20

• SU + meglitinide
• GLP-1 RA + DDP-4 inhibitors
• Two basal/intermediate insulins
• Two rapid/short-acting insulins
• SU/meglitinide + rapid/short-acting insulin