04 Thera VI T2DM Oral Therapies Diane

Question 1

What is the pathophysiology of the pancreas in T2DM?

Answer 1

Impaired insulin secretion. Progressive loss of beta cell function

Question 2

What is the pathophysiology of the liver in T2DM?

Answer 2

Impaired insulin sensitivity. Increased gluconeogenesis (glucose production)

Question 3

What is the pathophysiology of the muscle and adipose tissue in T2DM?

Answer 3

Insulin resistance. Decreased glucose uptake

Question 4

What is the pathophysiology of the GI tract in T2DM?

Answer 4

Site of glucose absorption. Decreased prandial response to glucose and incretin effect

Question 5

What are the ADA adult glycemic goals?

Answer 5

A1c < 7%. FPG 70-130. 2hr PP < 180

Question 6

What are the AACE adult glycemic goals?

Answer 6

A1c < 6.5%. FPG < 110. 2hr PP < 140

Question 7

What drugs are Biguanides?

Answer 7

Metformin

Question 8

What is the MOA of Metformin?

Answer 8

Activates AMP-kinase: Decreases hepatic glucose production, decreases GI glucose absorption, improves peripheral glucose sensitivity

Question 9

What is the A1c efficacy of Metformin?

Answer 9

Decreases it by 1-2%

Question 10

What is the positive side of using Metformin?

Answer 10

NO weight gain or hypoglycemia associated. Can also improve the lipid panel (Decrease TG and LDL)

Question 11

What is the Onset time of Metformin?

Answer 11

Days, max effect up to 2 weeks

Question 12

How is Metformin metabolized/excreted?

Answer 12

No hepatic metabolism. 100% renally excreted

Question 13

How is Metformin dosed?

Answer 13

Initial: 500mg BID or 850mg daily. Max: 2550mg/day (no added benefit > 2g/day)

Question 14

How is Metformin ER dosed?

Answer 14

Initial: 500mg/day. Max 2000mg/day

Question 15

What needs to be remembered about the administration of Metformin?

Answer 15

TAKE WITH FOOD. Titrate slowly

Question 16

What are the common ADRs associated with Metformin?

Answer 16

GI effects: N/V/D, flatulence, abdominal discomfort (these are less with ER)

Question 17

What are the counseling points with Metformin?

Answer 17

Recommend patients to take with food to decrease GI side effects. The side effects are transient, will improve over time

Question 18

What is a rare side effect of Metformin (BBW)?

Answer 18

Lactic Acidosis. Risk increases with renal impairment and hypoxemia. Labs will show an increase in lactate (>5mmol), decreased blood pH, and electrolyte abnormalities (increase in anion gap)

Question 19

What are the symptoms of Lactic Acidosis?

Answer 19

Very non-specific (need labs to prove it). N/V/D, hyperventilation, malaise, lethargy, myalgias

Question 20

What are the contraindications associated with Metformin?

Answer 20

Hypersensitivity. Renal dysfunction (Scr > 1.5 for men and > 1.4 for women). Acute or chronic metabolic acidosis. Radiological studies with iodinated contrast (hold 48 hours prior to and after procedure)

Question 21

What should you use caution with Metformin?

Answer 21

Chronic hepatic dysfunction (reduced lactate clearance). Hypoxic states (excessive alcohol, CHF, surgery)

Question 22

What are the indications for Sulfonylureas?

Answer 22

Considered second-line to be added on to metformin and combination with insulin or other oral agents (except meglitinides). Can be used first-line in patients who cannot tolerate metformin

Question 23

What are the main Sulfonylureas used?

Answer 23

Glimeperide (Amaryl). Glipizide (Glucotrol). Glyburide (DiaBeta, Micronase, Glynase)

Question 24

What is the MOA of Sulfonylureas?

Answer 24

Binds ATP-dependent K channels –> depolarization of B-cells –> Ca influx –> increase insulin release. Partially reverses insulin secretory defect associated with T2DM

Question 25

What is a drawback to Sulfonylurea use?

Answer 25

Effectiveness will decline over time

Question 26

How much do Sulfonylureas decrease A1c?

Answer 26

1-2%. All agents equally effective

Question 27

How are Sulfonylureas metabolized and eliminated?

Answer 27

Metabolism: Hepatic. Elimination: Renal (urine), feces

Question 28

Which Sulfonylurea has the fastest onset?

Answer 28

Glyburide (1h). Glipizide (1-3h). Glimepiride (2-3h)

Question 29

Which Sulfonylurea has the shortest duration of action?

Answer 29

Glipizide (10-14h). Glyburide (12-24). Glimepiride (24h)

Question 30

Which Sulfonylureas have active metabolites?

Answer 30

Only Glimepiride and Glyburide

Question 31

What are the CrCl levels that you need to use caution with the Sulfonylureas?

Answer 31

Glipizide (< 10). Glimepiride (< 22). Glyburide (< 50)

Question 32

Which Sulfonylureas need to be taken with food?

Answer 32

"-ride": Glimepiride and Glyburide

Question 33

When does Glipizide need to be taken?

Answer 33

Take 30 minutes before meals

Question 34

Which Sulfonylureas have BID dosing?

Answer 34

Glyburide and Glipizide

Question 35

Which Sulfonylureas have QD dosing?

Answer 35

Glimepiride and Glipizide ER

Question 36

What are the common ADRs associated with Sulfonylureas?

Answer 36

Hypoglycemia. Weight gain (2-5kg)

Question 37

What are the rare ADRs associated with Sulfonylureas?

Answer 37

GI (N, dypepsia). Photosensitivity. Skin rash

Question 38

Which Sulfonylurea is usually ok to use with Sulfa allergies?

Answer 38

Glimepiride

Question 39

What are contraindications for Sulfonylurea use?

Answer 39

Hypersensitivity. T1DM (they don't have working B-cells to release insulin). Diabetic Ketoacidosis

Question 40

When should you use caution when using a Sulfonylurea agent?

Answer 40

Sulfa allergy. Renal dysfunction

Question 41

When are Meglitinides recommended?

Answer 41

May be used first line in patients who cannot take metformin or in place of SFU in patients with irregular eating schedules

Question 42

What are the Meglitinide drugs?

Answer 42

Repaglinide (Prandin) and Nateglinide (Starlix)

Question 43

What is the MOA of Meglitinides?

Answer 43

Similar to SFU (increase insulin production). Fast onset and shorter duration. Target post-prandial glucose

Question 44

How much is A1c lowered by Meglitinides?

Answer 44

1-1.5%

Question 45

How are Meglitinides metabolized and eliminated?

Answer 45

Metabolism: Hepatic. Elimination: Renal (urine), feces

Question 46

What is the onset time for Meglitinides?

Answer 46

Nateglinide (20 hours). Repaglinide (15-60 hours)

Question 47

When are Meglitinides taken?

Answer 47

Taken with meals. Skip dose if skipping meal. Start with lowest possible dose (caution in elderly)

Question 48

What are the common ADRs associated with Meglitinides?

Answer 48

Hypoglycemia (Repaglinide > Nateglinide). Weight gain. HA. Upper respiratory infection

Question 49

When are Meglitinides contraindicated?

Answer 49

Hypersensitivity. T1DM. DKA. Repaglinide: concurrent gemfibrozil therapy

Question 50

When should you use caution before Meglitinide use?

Answer 50

Caution in renal/hepatic impairment

Question 51

When are Thiazolidinediones indicated?

Answer 51

Approved for monotherapy and combination therapy with metformin, DPP-4 inhibitors, incretin mimetics, SFU

Question 52

What are the Thiazolidinediones drugs?

Answer 52

Prioglitazone (Actos). Rosiglitazone (Avandia)

Question 53

What is the MOA of Thiazolidinediones?

Answer 53

Activate PPARy nuclear receptors (muscle and fat tissue). Decrease peripheral insulin resistance (insulin sensitizer). Decrease hepatic glucose output

Question 54

How much is A1c lowered by Thiazolidinediones?

Answer 54

1-1.5%

Question 55

How do Thiazolidinediones affect the lipid profile?

Answer 55

Pioglitazone: decrease TG and increase HDL. Rosiglitazone: Increase LDL

Question 56

What is the onset time for Thiazolidinediones?

Answer 56

Delayed. Up to 3 months for maximum effect. Works on gene translation, protein production

Question 57

How are Thiazolidinediones metabolized and eliminated?

Answer 57

Metabolism: Hepatic. Elimination: Urine and feces

Question 58

What is the BBW associated with Thiazolidinediones?

Answer 58

CHF (may cause or worsen CHF, not recommended for patients with symptomatic HF (class III and IV). Monitor patients for s/sx of HF after initiation and when increasing dose

Question 59

What is cardiovascular safety like for Thiazolidinediones?

Answer 59

43% higher incidence of MI with Rosiglitazone use. Pioglitazone have some CV protection

Question 60

What is the use of Rosiglitazone limited to?

Answer 60

Patients already being successfully treated with it. Patients who cannot be controlled with other anti-diabetic medicines. Consulted with MD and do not wish to use pioglitazone containing medicines

Question 61

What is a major risk of Pioglitazone use?

Answer 61

Risk of bladder cancer increased with increasing dose (reaching statistical significance after 24 months). Do not use Pioglitazone for longer than 1 year. Counsel patients to report s/sx of blood in urine, urinary urgency, pain on urination, or back or abdominal pain

Question 62

What is the administration of Thiazolidinediones like?

Answer 62

Once daily dosing. Can take without regard to meals. Brand only. No renal dose adjustment

Question 63

What are the common ADRs associated with Thiazolidinediones?

Answer 63

Weight gain. Edema. Increased subcutaneous adipose

Question 64

What are the rare ADRs associated with Thiazolidinediones?

Answer 64

Hepatic failure. Decreased WBC, Hgb, and platelets

Question 65

What are the contraindications to Thiazolidinediones use?

Answer 65

NYHA Functional Class III/IV HF. ALT > 2.5x upper normal limit

Question 66

When should you use caution before Thiazolidinediones use?

Answer 66

Cardiac disease. Edema. Hepatic disease. Bladder cancer (Pioglitazone)

Question 67

When are alpha-Glucosidase Inhibitors indicated?

Answer 67

Approved for monotherapy or combination with metformin

Question 68

What are the alpha-Glucosidase Inhibitors drugs?

Answer 68

Acarbose (Precose). Miglitol (Glyset)

Question 69

What is the MOA of alpha-Glucosidase Inhibitors?

Answer 69

Decrease absorption of carbohydrates in small intestines. Inhibit small intestine brush border enzymes. Targets post-prandial glucose

Question 70

How much is the A1c lowered with alpha-Glucosidase Inhibitors?

Answer 70

0.5-1%

Question 71

What is the absorption like for alpha-Glucosidase Inhibitors?

Answer 71

Acarbose is poor (1-2%). Miglitol has saturable absorption (25mg completely absorbed, 100mg ~50-70% absorption)

Question 72

How are alpha-Glucosidase Inhibitors metabolized and eliminated?

Answer 72

Metabolism: Acarbose metabolized by intestinal bacteria and digestive enzymes in GI, Miglitol is not metabolized. Excretion: Renal (miglitol), fecal (acarbose)

Question 73

What is the administration of alpha-Glucosidase Inhibitorslike?

Answer 73

Taken with meals. Skip dose if skipping meal. Slow titration - based on one hour post-prandial and to decrease GI upset

Question 74

What are the common ADRs assocaited with alpha-Glucosidase Inhibitors?

Answer 74

GI side effects (gas, bloating, diarrhea)

Question 75

What are the rare ADRs associated with alpha-Glucosidase Inhibitors?

Answer 75

Increased LFTs. Hepatic failure

Question 76

What are the contraindications for alpha-Glucosidase Inhibitors?

Answer 76

Chronic GI disease (IBD, Crohns, obstruction)

Question 77

When should you use caution before using alpha-Glucosidase Inhibitors?

Answer 77

Renal/hepatic impairment

Question 78

What are the indications for Dipeptidyl Peptidase-4 (DPP-4) Inhibitors?

Answer 78

Approved for monotherapy and in combination with metformin, TZDs, SFUs

Question 79

What are the DPP-4 Inhibitors drugs?

Answer 79

Sitagliptin (Januvia). Saxagliptin (Onglyza). Linagliptin (Tradjenta)

Question 80

What is the MOA of DPP-4 Inhibitors?

Answer 80

Inhibit DPP-4 --> increase endogenous incretins (GLP-1 and GIP). Early satiety. Increase insulin release in response to ingested glucose. Decrease pancreatic secretion of glucagon. Slowed gastric emptying

Question 81

How much is A1c lowered with DPP-4 Inhibitors?

Answer 81

0.5-1%

Question 82

Which DPP-4 Inhibitors are excreted renally?

Answer 82

Sitagliptin. Saxagliptin

Question 83

Which DPP-4 Inhibitor is excreted 80% bile (enterohepatic), minimal renal?

Answer 83

Linagliptin

Question 84

How is Sitagliptin renally adjusted?

Answer 84

CrCl 30-50: 50mg daily. CrCl < 30: 25mg daily

Question 85

How is Saxagliptin renally adjusted?

Answer 85

CrCl < 50: 2.5mg daily

Question 86

How is Linagliptin renally adjusted?

Answer 86

No renal adjustment needed

Question 87

What are the ADRs associated with Sitagliptin?

Answer 87

GI side effects. URI. Nasopharyngitis

Question 88

What are the ADRs associated with Saxagliptin?

Answer 88

Peripheral edema. Hypoglycemia

Question 89

What are the ADRs associated with Linagliptin?

Answer 89

Nasopharyngitis. Hypoglycemia

Question 90

What is the combination product: Metformin + Glyburide?

Answer 90

Glucovance

Question 91

What is the combination product: Metformin + Glipizide?

Answer 91

Metaglip

Question 92

What is the combination product: Metformin + Pioglitazone?

Answer 92

Actoplus Met

Question 93

What is the combination product: Metformin + Rosiglitazone?

Answer 93

Avandamet

Question 94

What is the combination product: Metformin + Sitagliptin?

Answer 94

Janumet

Question 95

What is the combination product: Metformin + Linagliptin?

Answer 95

Jentadueto

Question 96

What is the combination product: Glimeperide + Pioglitazone?

Answer 96

Duetact

Question 97

What is the combination product: Glimperide + Rosiglitazone?

Answer 97

Avandaryl

Question 98

What are your best drug choices to avoid weight gain?

Answer 98

Metformin. DPP-4 Inhibitors

Question 99

What are the best drug choices to avoid GI symptoms?

Answer 99

SFUs. Meglitinides. TZDs. DPP-4 Inhibitors

Question 100

What are the best drug choices to avoid Hypoglycemia?

Answer 100

Metformin. TZDs. DPP-4 Inhibitors

Question 101

What are the best drug choices with impaired renal function?

Answer 101

Meglitinides. TZDs

Question 102

What are the best drug choices with impaired hepatic function?

Answer 102

SFUs. DPP-4 Inhibitors

Question 103

What are the best drug choices with impaired CV/pulmonary function?

Answer 103

SFUs. Meglitinides. DPP-4 Inhibitors