Pharm Management of T2D

Question 1

Basal vs prandial glucose

Answer 1

Basal: suppresses glucose production between meals and overnight
Prandial: facilitates glucose uptake after meals

Question 2

When insulin is subcutaneously injected, it forms…

Answer 2

Hexamers (these minimally diffuse, need to break up into monomer form)

Question 3

4 current basal insulins

Answer 3

Insulin glargine
Insulin glargine U300
Insulin detemir
Insulin degludec

Question 4

3 types of current bolus insulins

Answer 4

Human regular insulin (humulin R, novolin Toronto)
Analogue rapid insulins (aspart, lispro, glulisine)
Analogue ultra-rapid insulins (ultra-rapid aspart)

Question 5

General mechanism of action for

1. Metformin
2. Sulfonylureas
3. Thiazolidinediones
4. Incretins
5. SGLT2 inhibitors
6. Alpha-glucosidase inhibitors

Answer 5

1. Decreases hepatic glucose output, decreases insulin resistance
2. Increases insulin secretion
3. Decreases insulin resistance
4. Increases insulin secretion, decreases glucose output, decreases gastric emptying
5. Increases urinary glucose excretion
6. Decreases carb breakdown/absorption

Question 6

Metformin mechanism

Answer 6

Overall: Decreases hepatic glucose output, decreases insulin resistance
Decrease hepatic glucose production through mild inhibition of the mitochondrial respiratory-chain complex 1
Decrease intestinal glucose absorption
Anti-oxidant properties of metformin on endothelial cells

Question 7

Metformin
4 advantages
2 disadvantages

Answer 7

Pros: effective glucose lowering, no significant hypoglycemia, durable effect, not associated with weight gain or CV side effects
Cons: GI side effects, rare lactic acidosis

Question 8

Examples of sulfonylureas

Answer 8

-ide drugs
Glyburide
Gliclazide
Glimepiride
Repaglinide
Nateglinide

Question 9

Sulfonylurea mechanism

Answer 9

Act at the beta cell
Block the K ATPase channel, inhibit K efflux, cell depolarizes, opens voltage-dependent Ca channel, Ca influx, release of insulin from vesicles

Question 10

Sulfonylurea advantages and disadvantages

Answer 10

Pros: cheap, easy to give, effective at lowering glucose
Cons: prone to weight gain, risk of hypoglycemia

Question 11

Incretins

Answer 11

GI hormones (GIP and GLP1) that are stimulated by food and inactivated by DPP-4
They augment physiologic insulin secretion

Question 12

How do GLP-1 receptor agonists and DPP-4 inhibitors work?

Answer 12

They prevent the breakdown of incretins (DPP4 inhibitors) or directly stimulate the GLP1 receptor (GLP1 RAs) to stimulate the beta cell to secrete insulin

Question 13

4 GLP-1 actions

Answer 13

Decreased appetite
Slows gastric emptying
Decreased hepatic glucose output
Increased insulin secretion (glucose dependent)

Question 14

SGLT2 inhibitors advantages and disadvantages

Answer 14

Pros: easy to administer, effective glucose lowering, promotes weight loss, lowers BP, low risk of hypoglycemia, CV benefits in high risk patients
Cons: polyuria, frequency, volume depletion, hyperkalemia, yeast infections, rare cases of euglycemia DKA

Question 15

Thiazolidinediones mechanism

Answer 15

PPAR-y activators (on adipose)
Reduces insulin resistance, modifies adipocyte differentiation, inhibits VEGF-induced angiogenesis, reduces leptin levels

Question 16

TZDs pros and cons

Answer 16

Pros: easy to admin, effective glucose lowering, durable
Cons: cost/coverage, side effects (weight gain from fat storage, edema, worsens CHF, bone fractures in osteoporosis)
Only use these in younger men now

Question 17

a-glucosidase inhibitor mechanism

Answer 17

Ex: acarbose
Binds to glucosidase enzyme in gut
Competitively inhibits the breakdown of non-absorbable complex polysaccharides
Reduces monosaccharide absorption (glucose)

Question 18

What is the preferred first line therapy? Why?

Answer 18

Metformin

It is associated with lower all-cause mortality and CV disease mortality than sulfonylureas

Question 19

In T2D, when would you start on insulin as an initial choice of therapy?

Answer 19

When there is symptomatic hyperglycemia and/or metabolic decompensation (polyuria, polydipsia, weight loss, volume depletion)

Question 20

1. 3 drugs with low risk for hypoglycemia

1. 2 drugs with high risk for hypoglycemia

Answer 20

1. metformin, incretin agents, SGLT2 inhibitors

2. insulin, sulfonylureas

Question 21

1. 2 drugs that cause weight loss

2. 3 drugs that cause weight gain

Answer 21

1. GLP-1 analogs, SGLT2 inhibitors

2. insulin, TZDs, sulfonylurea

Question 22

2 drugs that are CV protective

Answer 22

SGLT2 inhibitors

GLP-1 agonists