Module 10: Diabetes (a) Flashcards
1
Q
Glycemic Targets for DM Treatment
A
- A1C <7%
- Preprandial capillary plasma glucose 80-130 mg/dL
- Peak postprandial capillary plasma glucose <180 mg/dL
2
Q
Glycemic Control A1C
-When to set Less Stringent Goal?
A
- Pt w/ limited life expectancy
- Pt where the harms of treatment are greater than benefits (Severe hypoglycemia)
- Advanced complications & Extensive co-morbidities
- Long-standing DM w/ goal difficult to achieve despite good education, multiple agents including insulin
A1C < 8% for above situations
3
Q
Pharmacologic Approaches to DMT2 Tx
-Classes and Med Examples
A
- Biguanide — Metformin
- DPP4 inhibitors — end in “gliptin”
- GLP1 RA’s (receptor agonists) — end in “glutide”
- SGLT2 inhibitors — end in “flozin”
- Sulfonylureas — end in “ide”
- Glinides — end in “glinide”
- Thiazolidinediones — end in “glitazone”
4
Q
Pharmacologic Approaches to DM Tx
-“Ominous Octet”
A
- Impaired insulin secretion —DPP4i, GLP-1 RA, SUs, Glinides
- Decreased incretin effect — DPP4i GLP-1 RAs
- Increased lipolysis — TZDs, Metformin
- Increased glucose reabsorption — SGLT2i
- Decreased glucose uptake —TZD, Metformin
- Neurotransmitter dysfunction —GLP-1 RA, bromocriptine
- Increased hepatic glucose production —Metformin
- Increased glucagon secretion —DPP4i, GLP-1RAs
5
Q
Pharmacologic Approaches to DM Tx
-To Optimally manage T2DM
A
- Therapy should be individualized based on known pathophysiologic defects
- Multiple agents are necessary to target different aspects of this disorder
6
Q
Pharmacologic Approaches to DM Tx
-Which Med for T2DM
A
- Consider How high A1C is? — Most Potent DM med will lower A1c by 2%
- Safety consideration — Age, renal/hepatic function, co-morbidities
- Cost — Some are VERY expensive
- Adverse Effects/Tolerability — Hypoglycemia & Weight Gain
- Complexity of regimen — Easy leads to better adherence
- PATIENT PREFERENCE — Shared decision making**TEST
—If patient doesn’t want an injectable, don’t give them one
7
Q
Oral DM Medications
-Metformin
A
- Biguanide class
- FIRST LINE therapy for T2 DM W/OUT CONTRAINDICATIONS
- May be used for prevention of T2DM/Prediabetes (No FDA approval) - MOA — Decreases hepatic glucose production
- Improves insulin sensitivity
8
Q
Oral DM Medications
-Metformin Benefits
A
- Works well/good A1C lowering
- Favorable effects on serum lipids
- Usually mild weight loss
- Doesn’t cause hypoglycemia as Mono-therapy
9
Q
Oral DM Medications
-Metformin A/E’s
A
- GI — Nausea, Diarrhea, abdominal pain TEST
—Extended Release LOWERS GI S/E’s - Can Cause Vit B12 deficiency — check for anemia, peripheral neuropathy — periodically monitor serum B12 levels
- 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
10
Q
Oral DM Medications
-Metformin Dosing
A
- Start w/ 500mg QD and gradually titrate up to MAX of 2G/Day
- Take w/ food
- Strategies to decrease GI S/E’s
- Extended Release version
- Take w/ food
- Gradual Titration
11
Q
Oral DM Medications
-Metformin Lactic Acidosis Risk??
A
- 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 - STOP Metformin if pt develops a condition associated w/ Hypoxemia, dehydration or sepsis
12
Q
Oral DM Medications
-Metformin Use w/ Renal Impairment?
A
- Monitor eGFR NOT creatinine — eGFR is more accurate — Obtain baseline then test annually
- AVOID Metformin w/ eGFR <30 Ml/min/1.73 M2
13
Q
Oral DM Medications
-Renal Impairment and Metformin
A
- If eGFR is 30-45 mL/Min/1.73 m2
- Initiating Metformin is NOT RECOMMENDED - If eGFR falls in this range DURING therapy
- Assess benefits and risk of continuing treatment
- Reduce Metformin dose by 1/2 (MAX 1G/day) - Usually held for patients undergoing contrast-dye procedures until renal function is reassessed
14
Q
Major Second-Line DM Agents
-GLP-1 Agonists “utide”
A
- Incretin Therapy — Mimics GLP-1 action — glucose-dependent release of insulin, suppression of glucagon
- Additional MOA — delays gastric emptying, suppresses appetite
15
Q
Major Second-Line Agents
-GLP-1 RA
A
- Weight loss; increased satiety
- CV benefits
- Low hypoglycemia risk
- Good A2C lowering
16
Q
Major Second-Line Agents
-GLP-1 RA BLACK BOX WARNING**
A
- Causes thyroid C-cell tumors in rats and mice
- Contraindicated in patients w/ a personal or family hx of MTC and in Pt’s w/ multiple endocrine neoplasia syndrome type 2 (MEN 2)
17
Q
Major Second-Line Agents
-SGLT-2-inhibitors “Flozin”
A
- Promotes urinary excretion of glucose by preventing glucose reabsorption
18
Q
Major Second-Line Agents
-SGLT2-I Benefits
A
“Flozin”
- Low hypoglycemia risk
- Weight loss
- Mild BP reduction
- Demonstrated CV Benefits
- Benefit in diabetic kidney disease w/ albuminuria
- Some have demonstrated benefit in HFrEF**TEST
19
Q
Major Second-Line Agents
-SGLT2 Inhibitors A/E’s
A
- Genital, GU tract infections
- Dehydration, hypotension
- Post-marketing reports of DKA w/ SGLT2i — Usually “Euglycemic”
20
Q
SGLT2i FDA Warnings
A
- Cases of Rare but LIFE-THREATENING bacterial infection of the genitals — necrotizing fasciitis of the perineum, or Fournier’s gangrene
21
Q
Major Second-Line Agents
-Sulfonylurea’s
A
- Oldest class of oral hypoglycemic agents
2. Ex: Glipizide (Shortest-acting)
22
Q
Major Second-Line Agents
-Sulfonylurea’s Info
A
- Initially very effective in lowering A1C
- A/Es
- Moderate hypoglycemia & Weight gain
- Increased risk of hypoglycemia in combo w/ other DM meds - Caution in Sulfonamide **allergy, renal/hepatic impairment
23
Q
Incretins
-DPP-4 Inhibitors “gliptin”
A
- MOA — Inhibits the intestinal enzyme, DPP-4 — Increases endogenous incretins — glucose-dependent release of insulin; suppression of glucagon
- Doesn’t cause hypoglycemia & Weight neutral
- Cons
- Low A1C lowering <1%
- Reports of acute pancreatitis — Avoid in patients w/ pancreatitis hx
- Heart Failure risk
24
Q
Thiazolidinediones
-Info
A
- Pioglitazone is preferred medication in this class —Can be considered alternative in pt’s who cannot take Metformin
- MOA
- Increase insulin receptor sensitivity
- Deases hepatic glucose production
- Enhance glucose uptake in muscle cells
25
Q
Thiazolidinediones
-A/E’s
A
- Weight gain
- Edema
- Increased risk of fractures
- Anemia
- Hepatotoxicity (Monitor LFTs)
26
Q
Thiazolidinediones
-Contraindications?
A
- Contraindicated in HEART FAILURE
- Avoid in
- increased fracture risk
- Active or hx of bladder cancer (pioglitazone)
- Active liver disease
27
Q
Alpha-Glucosidase Inhibitors (AGIs)
-Info
A
- Acarbose (Precose) ; Miglitol (Glyset)
- MOA — Delays glucose digestion and absorption
- Primary A/E is GI TEST
