Module 10: Diabetes (a)

Question 1

Glycemic Targets for DM Treatment

Answer 1

1. A1C <7%
2. Preprandial capillary plasma glucose 80-130 mg/dL
3. Peak postprandial capillary plasma glucose <180 mg/dL

Question 2

Glycemic Control A1C

-When to set Less Stringent Goal?

Answer 2

1. Pt w/ limited life expectancy
2. Pt where the harms of treatment are greater than benefits (Severe hypoglycemia)
3. Advanced complications & Extensive co-morbidities
4. Long-standing DM w/ goal difficult to achieve despite good education, multiple agents including insulin

A1C < 8% for above situations

Question 3

Pharmacologic Approaches to DMT2 Tx

-Classes and Med Examples

Answer 3

1. Biguanide — Metformin
2. DPP4 inhibitors — end in “gliptin”
3. GLP1 RA’s (receptor agonists) — end in “glutide”
4. SGLT2 inhibitors — end in “flozin”
5. Sulfonylureas — end in “ide”
6. Glinides — end in “glinide”
7. Thiazolidinediones — end in “glitazone”

Question 4

Pharmacologic Approaches to DM Tx

-“Ominous Octet”

Answer 4

1. Impaired insulin secretion —DPP4i, GLP-1 RA, SUs, Glinides
2. Decreased incretin effect — DPP4i GLP-1 RAs
3. Increased lipolysis — TZDs, Metformin
4. Increased glucose reabsorption — SGLT2i
5. Decreased glucose uptake —TZD, Metformin
6. Neurotransmitter dysfunction —GLP-1 RA, bromocriptine
7. Increased hepatic glucose production —Metformin
8. Increased glucagon secretion —DPP4i, GLP-1RAs

Question 5

Pharmacologic Approaches to DM Tx

-To Optimally manage T2DM

Answer 5

1. Therapy should be individualized based on known pathophysiologic defects
2. Multiple agents are necessary to target different aspects of this disorder

Question 6

Pharmacologic Approaches to DM Tx

-Which Med for T2DM

Answer 6

1. Consider How high A1C is? — Most Potent DM med will lower A1c by 2%
2. Safety consideration — Age, renal/hepatic function, co-morbidities
3. Cost — Some are VERY expensive
4. Adverse Effects/Tolerability — Hypoglycemia & Weight Gain
5. Complexity of regimen — Easy leads to better adherence
6. PATIENT PREFERENCE — Shared decision making**TEST
   —If patient doesn’t want an injectable, don’t give them one

Question 7

Oral DM Medications

-Metformin

Answer 7

1. Biguanide class
2. FIRST LINE therapy for T2 DM W/OUT CONTRAINDICATIONS
   - May be used for prevention of T2DM/Prediabetes (No FDA approval)
3. MOA — Decreases hepatic glucose production
   - Improves insulin sensitivity

Question 8

Oral DM Medications

-Metformin Benefits

Answer 8

1. Works well/good A1C lowering
2. Favorable effects on serum lipids
3. Usually mild weight loss
4. Doesn’t cause hypoglycemia as Mono-therapy

Question 9

Oral DM Medications

-Metformin A/E’s

Answer 9

1. GI — Nausea, Diarrhea, abdominal pain TEST
   —Extended Release LOWERS GI S/E’s
2. Can Cause Vit B12 deficiency — check for anemia, peripheral neuropathy — periodically monitor serum B12 levels
3. Contraindicated in patients w/ factors predisposing to lactic acidosis TEST

Board Exam Question — Metformin has GI effects and is contraindicated in patients w/ factors predisposing to lactic acidosis **TEST

Question 10

Oral DM Medications

-Metformin Dosing

Answer 10

1. Start w/ 500mg QD and gradually titrate up to MAX of 2G/Day
2. Take w/ food
3. Strategies to decrease GI S/E’s
   - Extended Release version
   - Take w/ food
   - Gradual Titration

Question 11

Oral DM Medications

-Metformin Lactic Acidosis Risk??

Answer 11

1. Predisposing factors/Contraindications
   - IMPAIRED Renal function (eGFR <30 mL/min) **TEST
   - ETOH
   - Liver Dz
   - Acute Heart failure at risk of hypoperfusion and Hypoxemia
   - Decreased tissue perfusion or hemodynamic instability d/t infection
   - Past Hx of lactic acidosis during Metformin
2. STOP Metformin if pt develops a condition associated w/ Hypoxemia, dehydration or sepsis

Question 12

Oral DM Medications

-Metformin Use w/ Renal Impairment?

Answer 12

1. Monitor eGFR NOT creatinine — eGFR is more accurate — Obtain baseline then test annually
2. AVOID Metformin w/ eGFR <30 Ml/min/1.73 M2

Question 13

Oral DM Medications

-Renal Impairment and Metformin

Answer 13

1. If eGFR is 30-45 mL/Min/1.73 m2
   - Initiating Metformin is NOT RECOMMENDED
2. If eGFR falls in this range DURING therapy
   - Assess benefits and risk of continuing treatment
   - Reduce Metformin dose by 1/2 (MAX 1G/day)
3. Usually held for patients undergoing contrast-dye procedures until renal function is reassessed

Question 14

Major Second-Line DM Agents

-GLP-1 Agonists “utide”

Answer 14

1. Incretin Therapy — Mimics GLP-1 action — glucose-dependent release of insulin, suppression of glucagon
   - Additional MOA — delays gastric emptying, suppresses appetite

Question 15

Major Second-Line Agents

-GLP-1 RA

Answer 15

1. Weight loss; increased satiety
2. CV benefits
3. Low hypoglycemia risk
4. Good A2C lowering

Question 16

Major Second-Line Agents

-GLP-1 RA BLACK BOX WARNING**

Answer 16

1. Causes thyroid C-cell tumors in rats and mice
2. Contraindicated in patients w/ a personal or family hx of MTC and in Pt’s w/ multiple endocrine neoplasia syndrome type 2 (MEN 2)

Question 17

Major Second-Line Agents

-SGLT-2-inhibitors “Flozin”

Answer 17

1. Promotes urinary excretion of glucose by preventing glucose reabsorption

Question 18

Major Second-Line Agents

-SGLT2-I Benefits

Answer 18

“Flozin”

1. Low hypoglycemia risk
2. Weight loss
3. Mild BP reduction
4. Demonstrated CV Benefits
5. Benefit in diabetic kidney disease w/ albuminuria
6. Some have demonstrated benefit in HFrEF**TEST

Question 19

Major Second-Line Agents

-SGLT2 Inhibitors A/E’s

Answer 19

1. Genital, GU tract infections
2. Dehydration, hypotension
3. Post-marketing reports of DKA w/ SGLT2i — Usually “Euglycemic”

Question 20

SGLT2i FDA Warnings

Answer 20

1. Cases of Rare but LIFE-THREATENING bacterial infection of the genitals — necrotizing fasciitis of the perineum, or Fournier’s gangrene

Question 21

Major Second-Line Agents

-Sulfonylurea’s

Answer 21

1. Oldest class of oral hypoglycemic agents

2. Ex: Glipizide (Shortest-acting)

Question 22

Major Second-Line Agents

-Sulfonylurea’s Info

Answer 22

1. Initially very effective in lowering A1C
2. A/Es
   - Moderate hypoglycemia & Weight gain
   - Increased risk of hypoglycemia in combo w/ other DM meds
3. Caution in Sulfonamide **allergy, renal/hepatic impairment

Question 23

Incretins

-DPP-4 Inhibitors “gliptin”

Answer 23

1. MOA — Inhibits the intestinal enzyme, DPP-4 — Increases endogenous incretins — glucose-dependent release of insulin; suppression of glucagon
2. Doesn’t cause hypoglycemia & Weight neutral
3. Cons
   - Low A1C lowering <1%
   - Reports of acute pancreatitis — Avoid in patients w/ pancreatitis hx
   - Heart Failure risk

Question 24

Thiazolidinediones

-Info

Answer 24

1. Pioglitazone is preferred medication in this class —Can be considered alternative in pt’s who cannot take Metformin
2. MOA
   - Increase insulin receptor sensitivity
   - Deases hepatic glucose production
   - Enhance glucose uptake in muscle cells

Question 25

Thiazolidinediones

-A/E’s

Answer 25

1. Weight gain
2. Edema
3. Increased risk of fractures
4. Anemia
5. Hepatotoxicity (Monitor LFTs)

Question 26

Thiazolidinediones

-Contraindications?

Answer 26

1. Contraindicated in HEART FAILURE
2. Avoid in
   - increased fracture risk
   - Active or hx of bladder cancer (pioglitazone)
   - Active liver disease

Question 27

Alpha-Glucosidase Inhibitors (AGIs)

-Info

Answer 27

1. Acarbose (Precose) ; Miglitol (Glyset)
2. MOA — Delays glucose digestion and absorption
3. Primary A/E is GI TEST