Diabetes

Question 1

Amylin analog

Answer 1

Adjunct therapy

Question 2

Oral antidiabetics may

Answer 2

Increase insulin secretion (known as secretagogues) • Increase insulin sensitivity • Work via other mechanisms

Question 3

Injectables

Answer 3

Insulin (often is needed eventually)
Amylin Analogues: e.g. Pramlintide (Symlin®) -
Incretin GLP-1 Mimetics: e.g. Exenatide (Byetta®

Question 4

Insulin human (Afrezza®)

Answer 4

rapid-acting insulin inhalation powder, administered before meals. Action peaks in 12-15 minutes. Must be used in combination with long-acting insulin in Type 1 diabetics. Contraindicated in asthma, COPD and lung cancer. Can cause acute bronchospasm.

Question 5

Amylin analogue MOA

Answer 5

slows gastric emptying, promotes
satiety, suppresses glucagon secretion,. The
hormone amylin is normally co-secreted with insulin.

Question 6

Incretin GLP-1 Mimetics

Answer 6

stimulates
glucose-dependent insulin secretion, inhibits
post-prandial release of glucagon, slows gastric
emptying, suppresses appetite

Question 7

Biguanides

Answer 7

increase sensitivity of insulin receptors, decrease

liver gluconeogenesis

Question 8

Sulfonylureas

Answer 8

stimulate insulin release (secretagogue) …watch for hypoglycemia

Question 9

Meglintinides

Answer 9

increase insulin release (secretagogue)

Question 10

α-Glucosidase Inhibitors

Answer 10

α-qGlucosidase Inhibitors: inhibit enzymes at GI brush border →
inhibits absorption of ingested carbohydrates

Question 11

Thiazolidinediones (TZDs)

Answer 11

Insulin sensitizers

Question 12

Dipeptidyl peptidase-4 (DPP-4) inhibitors

Answer 12

slow incretin
inactivation by DPP-4 enzyme → stimulate glucose-dependent
insulin release and inhibit post-prandial glucagon release

Question 13

Sodium-glucose co-transporter-2 (SGLT2) inhibitors

Answer 13

Reduce reabsorption of glucose by the kidneys

Question 14

Insulin

Answer 14

Indication – DM1, DM2, acute hyperglycemia
MOA – binds to insulin receptor, stimulating
translocation of glucose transporters (e.g., GLUT4 on
muscle and adipose cells), thereby facilitating glucose
movement into cells.

Adverse effects – hypoglycemia, lipohypertrophy, more
rarely lipoatrophy; weight gain, allergic reaction. •

Interactions - alcohol (inc. risk of hypoglycemia), oral DM
medications (inc. risk of hypoglycemia), β-blockers
(hypoglycemic unawareness)

Question 15

Hypoglycemia risk factors

Answer 15

Mismatch of insulin timing, amount or type for carbohydrate
intake, Oral secretagogues, without sufficient carbohydrate intake, Reduction in nutrient intake, Nausea/vomiting

Geriatric patients at higher risk for hypoglycemia

Question 16

Rapid acting

Answer 16

Aspart (NovoLog®) Lispro (Humalog®) Glulisine (Apidra®)

Question 17

Short acting

Answer 17

Regular/Human (Humulin® R, Novolin® R)

Question 18

Intermediate acting

Answer 18

NPH (Humulin® N, Novolin® N) Detemir (Levemir®) (lower doses)

Question 19

Long acting

Answer 19

Glargine (Lantus®, Toujeo®, Basaglar®) Detemir (Levemir®) (higher doses) Degludec (Tresiba®) – ultra-long-acting

Question 20

Keep in mind about insulin mixes

Answer 20

The rapid- or short-acting portion will generally determine the onset
• The intermediate-acting portion will generally determine the duration

Question 21

Rules for mixing insulins

Answer 21

Of the intermediate- and long-acting insulins
(NPH, detemir, glargine and degludec) ONLY
NPH can be mixed in the same syringe with rapid-
and short-acting insulins.

Do not mix detemir, glargine or degludec in the same syringe with rapid or short-acting insulin.

Question 22

Insulin needs are decreased by

Answer 22

by exercise (generally speaking), first trimester of pregnancy and immediate post-partum period

Question 23

Define basal and bolus

Answer 23

Basal: The steady, low level of insulin constantly
secreted by the pancreas

Bolus: The spikes in insulin secretion stimulated by
glucose ingestion, especially at meals

Question 24

Correctional insulin

Answer 24

is often given at mealtimes (in addition to carb-related), to account for the actual blood glucose reading prior to the meal.

Question 25

In patient scenarios requiring insulin

Answer 25

Type 1 diabetics may require more than their
normal dose
– Type 2 diabetics who are not insulin-dependent
may need it
– Patients receiving total parenteral nutrition may
require it
– Even people who do not have a history of diabetes
may require insulin and they or their families will
be asking you why you are giving it to them.

Question 26

Somogyi Effect

Answer 26

Undetected hypoglycemia followed by rebound

hyperglycemia in AM

Question 27

Dawn Phenomenon

Answer 27

Rise in BG between 2-8 AM secondary to rise in counterregulatory hormones (inc. glucagon, growth hormone, cortisol) that are normally released, even by healthy people → patient will be hyperglycemic in AM

Question 28

Pramlintide

Remember TIDE - gastric water jug

Answer 28

Indication – For Type 1 & insulin-using Type 2 patients (Used as supplement to Insulin)
Mechanism – mimetic of human amylin. Slows gastric
emptying, suppresses glucagon secretion, promotes satiety (prevents postprandial hyperglycemia)

ADE: nausea, headache, hypoglycemia (due to concomitant insulin administration); caution if gastroparesis

Question 29

Metformin

Answer 29

Class: Biguanide
• Indication – Type 2 DM (First-line therapy in T2DM).
• Mechanism – increases sensitivity of insulin receptors AND
decreases liver gluconeogenesis (weight-neutral, very low risk
of hypoglycemia)

Adverse effects – A/N/V/D (esp. first 2-3 weeks), lactic acidosis; avoid in significant hepatic or renal dysfunction, alcoholism; long-term use associated with B contribute to neuropathy.

Interactions: alcohol (increases risk of lactic acidosis), caution
with sulfonylureas, other DM medications (may enhance
hypoglycemia risk)

Question 30

Metformin contraindications

Answer 30

Contraindicated in patients with an eGFR < 30. Test eGFR before initiating treatment with metformin.
– Supplement with B12 if testing indicates deficiency

Question 31

Metformin consideration

Answer 31

If eGFR < 60 or if the patient has a
history of liver disease, alcoholism,
or heart failure, metformin should be
discontinued immediately prior to
and for 48 hours after any radiologic
procedure involving IV iodinated
contrast material.

Question 32

Glipizide (sulfonylurea swan)

Answer 32

Class: Sulfonylurea
• Indication – Type 2 DM
• Mechanism – stimulates insulin release by blocking ATP-sensitive potassium channels → Ca++ influx → insulin release. Secretagogue.

Take 30 mins. prior to first meal of the day and another
meal if taking BID. Important to teach about taking with meals!
ADE: hypoglycemia, weight gain – hepatotoxicity, rash; avoid in late pregnancy (1 month prior to delivery);
Interactions: alcohol (potentiates hypoglycemic effects), β-blockers (may mask hypoglycemia Sx, can also suppress insulin release); DPP-4 inhibitors

Question 33

Sulfonyurea MOA

Answer 33

This mechanism of insulin release by blocking
ATP-sensitive potassium channels works the same as
if endogenous glucose had stimulated insulin release.
However, oral secretagogues do not require the
presence of glucose to work. This is the main reason
they can cause hypoglycemia.

Question 34

Repaglinide (think gliding swan)

Answer 34

Class: Meglitinide (also known as glinides)
• Indication – Type 2 DM
• Mechanism – same as sulfonylureas. Secretagogue

TAKE WITH FOOD!

Adverse effects – hypoglycemia, weight gain (fat lady by tree)
Interactions: Gemfibrozil can inhibit metabolism of repaglinide → inc. risk of hypoglycemia; alcohol, β-blockers.

Question 35

Considerations for:

Secretagogues (sulfonylureas, meglitinides)

Answer 35

Stimulate insulin release regardless of food intake. → Risk of hypoglycemia.
• Take them with (or right before) meals.
• If N/V/A, skip the secretagogue until able to eat again!

Question 36

Acarbose

Answer 36

• Class: α-Glucosidase inhibitor
• Indication – Type 2 DM
• Mechanism – inhibit α-Glucosidase enzyme at GI brush
border → slowed absorption & digestion of carbohydrates.

TAKE BEFORE EATING

• Adverse effects – abdominal distension, cramps,
flatulence, and diarrhea; hepatic dysfunction with long-term
use, (monitor LFTs), decreased iron absorption → anemia;
caution if bowel obstruction
• Interactions – metformin (additive GI side effects), oral iron

Question 37

Pioglitazone

Answer 37

• Class: Thiazolidinedione (TZD)
• Indication – Type 2 DM
• Mechanism – PPAR (peroxisome proliferator-activated
receptor) gamma agonist; increases tissue insulin
sensitivity, decreases hepatic glucose production
• Adverse effects – fluid retention, edema, HF, anemia,
↑ LDL-C but ↑ HDL-C and ↓TGs, risk for bladder cancer, fractures in women; hepatotoxicity
• Interactions: combination with insulin increases risk for
hypoglycemia; CYP2C8 inhibitors (atorvastatin, ketoconazole) and CYP2C8 inducers (rifampin, cimetadine)

Question 38

Sitagliptin

Answer 38

• Class: DPP-4 Inhibitor
• Indication – Type 2 DM – third-line drug, usually used in combo with other anti-diabetic medications
• Mechanism – inhibits DPP-4 enzyme and prevents inactivation of
incretins.

Interaction: Sulfonylureas

Adverse effects: low risk of hypoglycemia when used alone.
Increased risk of hypoglycemia when combined with
sulfonylurea. Headache, edema, acute renal failure, upper
respiratory infection, rare risk of pancreatitis, serious
hypersensitivity reactions, Stevens-Johnson Syndrome.
Reduce dose in renal disease.

Question 39

Incretin function

Answer 39

Incretin hormones found in the gut (such as GLP-1) normally
increase insulin synthesis and release and also inhibit
glucagon. DPP-4 enzyme normally inactivates incretins.
Sitagliptin inhibits DPP-4,thus increasing and prolonging
action of incretins → ↑insulin and ↓ post-prandial glucagon.

Question 40

Benefit to DPP-4 inhibitors on hypoglycemia

Answer 40

Risk of hypoglycemia when used alone is low because
sitagliptin extends the action of incretins, which require the
presence of glucose to increase insulin secretion, as we will
see shortly.

Question 41

Canalifglozin

Answer 41

Class: SGLT2 inhibitor
• Indication – Type 2 DM
• Mechanism: Sodium-glucose co-transporter-2 (SGLT2)
inhibitor in the kidney. Newest type of oral diabetes
medication, first approved in 2013. Prevents reuptake of most
filtered glucose by the kidney → glucose is diuresed and
not returned to circulation.
• Dose: 100 – 300 mg daily if eGFR > 60, 100 g daily of eGFR
between 45-60; do not give to patients with eGFR < 45

Adverse effects: increased urination (osmotic diuresis), hypotension (potential for volume depletion), hypoglycemia (when used with insulin or secretagogues), hyperkalemia, decreased renal function (increased creatinine and decreased eGFR), acute kidney injury, urinary tract infection, genital yeast infections, bone fractures (as early as 12 weeks after initiating the drug) and atypical
ketoacidosis.

Interactions: Drug interactions: rifampin, phenytoin, phenobarbital,
ritonavir (all decrease effectiveness of canagliflozin), digoxin (serum concentration of digoxin will be increased).

– BBW: In 2017, FDA required BBW regarding increased
risk of leg and foot amputation with this mediction.

Question 42

Exenatide (think witch with stomach)

Answer 42

Class: Incretin mimetic/GLP-1 receptor agonist
• Indication – Type 2 DM
• Mechanism: incretin-mimetic, analog of GLP-1 hormone, activates
pancreatic receptors for GLP-1, increases glucose-dependent
insulin secretion AND decreases post-prandial glucagon, slows
gastric emptying, suppresses appetite
• Administer: injectable only - prefilled pen formulation
• Adverse effects: N/V/D, pancreatitis, nephrotoxicity, bile duct
and gallbladder disease, hypoglycemia when combined with some
oral DM medications, renal impairment, avoid in pregnancy
(animal studies show fetal harm)
Interaction: Can slow absorption of oral drugs, give oral drugs 1
hour before exenatide.

Question 43

Warnings with incretin mimetics

Answer 43

All incretin mimetics/GLP-1 analogs come with a BBW about
thyroid C-cell tumors, including medullary thyroid carcinoma,
due to increased incidence of these tumors in animal studies.