Dr. Rabadaba: Part 2=T2DM Flashcards Preview

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Flashcards in Dr. Rabadaba: Part 2=T2DM Deck (14)
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1

T2DM

Life stycle changes is more effective than metformin for treatment of T2DM

2

Metformin MOA

  • Binds to Oct1 receptor on Hepatocyte membrane
  • Mitochondria
    • inhibits complex 1 of ETC
    • causes increase in ADP and AMP/ATP ratio
      • Decrease ATP
      • increase ADP
  • AMP activates AMPK
  • AMPK:
    • inhibits gluconeogenesis
    • increases Lactate
      • decrease pyruvate
  • Overal: Decrease hepatic Glucoxse production

3

Metformin

  • first line agent to prevent T2DM in:
    • prediabetes: A1C
    • w/T2DM-monotherapy if
      • A1c: 6.5-7.5
      • within 1.5% of established goal
    • Dual therapy:
      • A1C- 7.5-8.9 or goal is not attained within 3-6 months
    • Triple therapy
      • Asymptomatic patients w/A1c>8.9%
  • Reduces insulin requirement but not A1c in T1DM

4

Metformin: Contraindications

  • Severe kidney disease
    • stage: 4-5
    • creatinine>1.7
    • eGFR<30
  • Liver Diseases
    • due to accumulation of lactate in the liver
  • Chronic Alcohol Consumption
    • women: 2 drinks a day
    • men: 4 drinks a day
  • >80 y.o.
  • Anemia-used with caution 

 

  • BUT 70% have at least 1 contraindication but lactic acidosis only ocurs in 6 per 100,000

5

Metformin Advantages vs Disadvantages

  • Advantages:
    • Reduces HbA1c by: 1-2%
    • rarely causes hypoglycemia
    • weight neutral (-2+ or +1%)
    • reduces major cardiac events including hospitalization for:
      • acute Myocardial infarction (AMI)
      • ischemic stroke
      • hemorrhagic stroke
      • transient ischmic attack (TIA)
      • cardiovascular death
  • Disadvantages:
    • causes GI discomforts
      • diarrhea, nausea, flatulence
      • decreaes overtime
      • reduced if taken with food
      • reduced risk with Metformin ER
    • Decreased vitamin B12 by 10-30%
    • Lactic acidosis
    • Accelerate kidney disease
      • 2x risk for dialysis

6

SGLT2 inhibitors

  • Sodium/glucose cotransporters inhibitors
  • Early Proximal tubule
    • causes blood glucose to be elminated in urine
  • Drugs: -Gliflozin
  • Dual therapy:
    • Canagliflozin + Metformin or Metformin XR
    • Ertugliflozin + Metformin
  • Triple Therapy:
    • Empagliflozin, linagliptin, metformin

7

SGLT2 inhibitors: Advantages vs Disadvantages

  • Advantages:
    • Reduce A1c by an extra 0.5-1.5%
    • Do not cause hypoglycemia
    • weight loss
    • Reduces MACE
      • canagliflozin only one FDA approved
    • Decrease CV death
      • Empagliflozine (decrease 35%)> Canagliflozine (decrease18%)
    • Slows the progression of CKD and HF
      • Empagliflozin and Canagliflozine> Dapagliflozin
  • Disadvantages:
    • Volume depletion
      • caution in eldery and pts on thiazides or loop diuretcis
      • patient sit upright for 2m in before standing to avoid orthostatic hypotension
    • FDA warning:
      • Risk of euglycemic DKA
      • suspend before surgery
      • serious UTI's
    • Canagliflozine
      • doubles the risk for toe/midfoot/leg  amputations
      • increase risk of bone fracture

8

SGLT2i: Favorable and Unfavorable effects in patients with T2DM

  • Favorable:
    • prevent Heart Failure
    • Preserve renal function
    • reduce
      • major adverse cardiovascular events (MACE)
      • Blood pressure
    • weight loss
    • Glycemia improvement
  • Unfavorable
    • Fractures
    • amputations
    • Genital infections
    • Diabetic Ketoacidosis

9

GLP-1 agonists: Drugs

  • 2nd line agents
  • -tide

10

GLP-1 Agonists: MOA

  • Activates GLP-1 receptor on B-cells
    • Gs coupled
    • causes nutrient induced insulin release
  • Promotes:
    • B-cell proliferation
    • insulin synthesis
  • Decreases gastric emptying
  • Increases satiety

11

GLP-1 Agonists: Advantages vs disadvantages

  • Advantages:
    • add 0.5-1% A1c 
      • dulaglutide-most efficient
    • All reduce MACE
      • Dulaglutide, Liraglutide, Semaglutide are FDA approved
    • low progression of CKD
      • Exanatide, liraglutide, dulaglutide
    • May reduce foot amputation
    • substantial weight reduction
    • no hypoglycemia
  • Disadvantages:
    • GI side effects
    • gastroporesis
    • pancreatitis
    • Avoid at eGFR<30
    • Semaglutide increases diabetic retionpathy
    • Exenatide-renal injury
    • DPP-4 inhibits need to be discontinuted

12

DPP-4 antagonists

  • -liptin
    • second line agents
  • liptin + metformin
    • first line fix-dose combination

13

DDP-4 antagonists: MOA

  • Inhibit DPP-4 activity
    • prolongs endogenous release of GLP-1 and GIP
  • increase glucose-induced insulin release
  • inhibit glucagon release

14

DDP-4 Antagonists: Advantages vs Disadvantages

  • Advantages:
    • reduce A1c
    • help with postprandial glucose excursion
    • weight neutral
    • Hypoglycemia is rare
      • can be used with patients at risk for hypoglycemia (elderly, depressed)
  • Disadvantages:
    • Upper respiratory tract infection
    • rhinitis
    • acute pancreatitis
    • joint pain
    • HF
    • rare hypersensitivity reactions