CH 60 Drugs for Diabetes Mellitus

Question 1

Type 1 DM

Answer 1

Onset: adolescence; abrupt
Etiology: autoimmune destruction of pancreatic beta cells
Tx: insulin therapy
- can sometimes start with metformin if some remaining pancreatic function

Symptoms:
- polyuria/nocturia
- polydipsia
- polyphagia
- weight loss

diabetic ketoacidosis (DKA) - common if insulin dosage is insufficient

Question 2

Type 2 DM

Answer 2

Onset: age 40+; gradual
Etiology: unknown, possibly hereditary; frequently obese
- insulin resistance
- inappropriate insulin secretion

Tx:
- Nonpharmacologic - often started for 3 month if HgA1C <7%
- Pharmacologic - metformin

Symptoms:
- asymptomatic initially
- polyuria/nocturia
- polydipsia
- polyphagia
- weight loss

Question 3

DM Short/Long-term Complications

Answer 3

Short term
- hyperglycemia
- hypoglycemia

Long term (Macrovascular)
- ↑ risk heart disease
- ↑ risk HTN
- ↑ risk stroke

Long term (Microvasculature)
- retinopathy
- nephropathy
– dx: protinuria
– tx: ACE & ARB (prophylactic)
- gastroparesis
– dx: gastric emptying study
– tx: metoclopramide (Reglan)
- peripheral neuropathy (feet & hands)
– dx: monofilament foot exam
- eretile dysfunction
- amuptations

Question 4

Diagnostic Criteria for DM:
Fasting Plasma Glucose

Answer 4

=/> 126mg/dL

Per American Diabetes Association (ADA) 2024 Guidelines

Question 5

Diagnostic Criteria for DM:
Random Glucose

Answer 5

=/> 200mg/dL
with signs and symptoms of DM

Per American Diabetes Association (ADA) 2024 Guidelines

Question 6

Diagnostic Criteria for DM:
Oral Glucose Tolerance Test (OGTT) 2hr plasma glucose

Answer 6

=/> 200mg/dL

Per American Diabetes Association (ADA) 2024 Guidelines

Question 7

Diagnostic Criteria for DM:
Hemoglobin A1C (HbG A1C)

Answer 7

6.5% +

Per American Diabetes Association (ADA) 2024 Guidelines

Question 8

Treatment Goal for DM

Answer 8

General: symptom management

HgB A1c: <7%
Fasting glucose: 70-130mg/dL
Post-prandial glucose: <180mg/dL

Question 9

Function of Insulin as a Glucose Regulating Hormone

Answer 9

• increases glucose transport
  – skeletal muscle
  – adipose tissue
• increases glycogen synthesis
• decreases gluconeogenesis

Question 10

Function of Glucagon as a Glucose Regulating Hormone

Answer 10

• promotes liver glycogen breakdown
• increases gluconeogenesis

Question 11

Other hormone affecting blood glucose:
Catecholamines

Answer 11

epinepherine and norepinephrine

• help to maintain blood glucose leves during sympathetic nervous system stimulation (fight or flight)

Question 12

Other hormone affecting blood glucose:
Growth Hormone

Answer 12

• increases protein synthesis in all body cells
• mobilizes fatty acids from adipose tissue
• antagonizes the effects of insulin

Question 13

Other hormone affecting blood glucose:
Glucocorticoids

Answer 13

• stimulates gluconeogenesis by the liver
• critical to survival during fasting/starvation

Question 14

Drug: insulin lispro (Humalog)

subcutaneous injection

Answer 14

Onset: 15-30 min
Peak: 0.5-2.5 hr
Duration: 3-6hr

Short-Duration: Rapid Acting

Question 15

Drug: insulin aspart (NovoLog)

subcutaneous injection

Answer 15

Onset: 10-20 min
Peak: 1-3 hr
Duration: 3-5 hr

Short-Duration: Rapid Acting

Question 16

Drug: insulin glulisine (Apidra)

subcutaneous injection

Answer 16

Onset: 10-15 min
Peak: 1-1.5 hr
Duration: 3-5 hr

Short-Duration: Rapid Acting

Question 17

Drug: regular insulin (Humulin R, Novolin R)

subcutaneous injection

Answer 17

Onset: 30-60 min
Peak: 1-5 hr
Duration: 6-10 hr

Short-Duration: Short Acting

Question 18

Drug: NPH insulin (Humulin N, Novolin N)

subcutaneous injection

Answer 18

Onset: 60-120 min
Peak: 6-14 hr
Duration: 16-24 hr

Intermediate Duration

Question 19

Drug: insulin glargine (U-100) (Lantus)

subcutaneous injection

Answer 19

Onset: 70 min
Peak: none
Duration: 18-24 hr

Long Duration

Question 20

Drug: insulin detemir (Levemir)

subcutaneous injection

Answer 20

Onset: 60-120 min
Peak: none
Duration: 12-24 hr

Long Duration

Question 21

Drug: insulin glargine (U-300) (Toujeo)

subcutaneous injection

Answer 21

Onset: 360 min
Peak: none
Duration: >24hr

Ultra-Long Duration

Question 22

Drug: insulin degludec (Tresiba)

subcutaneous injection

Answer 22

Onset: 30-90 min
Peak: none
Duration: >24 hr

Ultra-Long Duration

Question 23

Onset of Insulins (memory trick)

Answer 23

rapid - Huma/Novo LOG

You are an RN - you give insulin R then N
short - Humu/Novo LIN R
interm - Humu/Novo LIN N

Long - Lantus or Levemir
ulTra - Toujeo or Tresiba

Question 24

Insulin AE

AE: Adverse Effects

Answer 24

• hypoglycemia
• hypokalemia
• lipohypertrophy (rotate injection sites)
• allergic reactions

Question 25

Insulin DI | DI: Drug Interactions

Answer 25

- **beta blockers** - hypoglycemic unawareness (masks tachycardia, tremors, nervousness). Non-selective beta-blockers can worsen hypoglycemia through inhibiting glycogen breakdown - **cortiosteroids** - oppose insulin's action; hyperglycemia. Higher doses of insulin needed to maintain therapeutic effects

Question 26

Drug: **glucophage** (Metformin)

Answer 26

**Class:** Biguanide **MOA:** increases insulin sensitivity; decreases glucose production in liver **Tx:** T2DM; increase sensitivity to injectable insulin for new T1DM diagnoses **AE:** - **GI upset** - onset & dosage changes; typically resolved in 2 weeks - **lactic acidosis** - in presence of renal failure; -- can be used with GFR >45; ***CI GFR less than 30*** -- do not take w/in 48hrs of iodinated contrast (which can cause transient AKI) - **increase fertility** - regulates cycles

Question 27

Drug: **glipizide** (Glucotrol)

Answer 27

**Class:** Sulfonylurea **MOA:** Stimulate insulin release by binding to SUR1 on pancreatic β-cells (ATP-sensitive K⁺ channels) **Onset:** 1-2 hours **Dose:** 1-2 times daily **Tx:** Second-line T2DM **AE:** - Hypoglycemia (moderate) - weight gain **Notes:** - inexpensive $ - effective in reducing HgbA1c 1.25%

Question 28

Drug: **glyburide** (Diabeta; Glynase PresTab; Micronase)

Answer 28

**Class:** Sulfonylurea **MOA:** Stimulate insulin release by binding to SUR1 on pancreatic β-cells (ATP-sensitive K⁺ channels) **Onset:** 1-2 hours **Dose:** 1-2 times daily **Tx:** Second-line T2DM **AE:** - Hypoglycemia (moderate) - weight gain **Notes:** - inexpensive $ - effective in reducing HgbA1c 1.25%

Question 29

Drug: **glimerpiride** (Amaryl)

Answer 29

**Class:** Sulfonylurea **MOA:** Stimulate insulin release by binding to SUR1 on pancreatic β-cells (ATP-sensitive K⁺ channels) **Onset:** 1-2 hours **Dose:** 1-2 times daily **Tx:** Second-line T2DM **AE:** - Hypoglycemia (moderate) - weight gain **Notes:** - inexpensive $ - effective in reducing HgbA1c 1.25%

Question 30

Drug: **repaglinide** (Prandin)

Answer 30

**Class:** Meglitinide (non-sulfonylurea insulin secretagogues) **MOA:** Stimulate insulin release by binding to SUR1 on pancreatic β-cells; *different site than sulfonylurea and more transiently* **Onset:** 15-30 min **Dose:** Take 30min before meals (+/- dose if +/- meal) *Do not exceed 4 doses per day.* **Tx:** T2DM **AE:** - Hypoglycemia (lower risk if meal/dose skipped) - weight gain

Question 31

Drug: **nateglinide** (Starlix)

Answer 31

**Class:** Meglitinide (non-sulfonylurea insulin secretagogues) **MOA:** Stimulate insulin release by binding to SUR1 on pancreatic β-cells; *different site than sulfonylurea and more transiently* **Onset:** 15-30 min **Dose:** Take 30min before meals (+/- dose if +/- meal) *Do not exceed 4 doses per day.* **Tx:** T2DM **AE:** - Hypoglycemia (lower risk if meal/dose skipped) - weight gain

Question 32

Drug: **pioglitazone** (Actos)

Answer 32

**Class:** Thiazolidinediones (TZDs) **MOA:** increase glucose uptake by skeletal muscle & adipose cells; decrease gluconeogenesis in liver **Dose:** 1x per day w/ or w/o food **Tx:** T2DM **AE:** - Hypoglycemia (lower risk than sulfonylurea) - weight gain - fluid retention - **CI in CHF** - liver toxicity - monitor LFTs q6months - increased lipids - monitor triglycerides q6months **Notes:** - expensive $$ - effective in reducing HgbA1c - **caution in use w/ insulins**, as they also cause fluid retention

Question 33

Drug: **acarbose** (Precose)

Answer 33

**Class:** Alpha-Glucosidase Inhibitor **MOA:** delays intestinal carbohydrate absorption; reduces post-prandial glucose spike **Dose:** w/ first bite of food; skip if meal skipped **Tx:** T2DM **AE:** - Hypoglycemia - must be treated w/ Dextrose - GI effects - distention, flatus, diarrhea - liver impairment - monitor LFTs **DI:** - insulin, sulfonylureas, ginseng - increases hypoglycemia - Metformin - worsens GI effects - Estrogen, thiazides, steroids, phenothiazines

Question 34

Drug: **miglitol** (Glyset)

Answer 34

**Class:** Alpha-Glucosidase Inhibitor **MOA:** delays intestinal carbohydrate absorption; reduces post-prandial glucose spike **Dose:** w/ first bite of food; skip if meal skipped **Tx:** T2DM **AE:** - Hypoglycemia - must be treated w/ Dextrose - GI effects - distention, flatus, diarrhea - liver impairment - monitor LFTs **DI:** - insulin, sulfonylureas, ginseng - increases hypoglycemia - Metformin - worsens GI effects - Estrogen, thiazides, steroids, phenothiazines

Question 35

Drug: **sitagliptin** (Januvia)

Answer 35

**Class:** DPP-4 inhibitor (dipeptidyl peptidase-4 inhibitor) **MOA:** - Inhibits the enzyme DPP-4, which normally breaks down incretin hormones like: -- GLP-1 (glucagon-like peptide-1) -- GIP (glucose-dependent insulinotropic peptide) - increases levels and prolongs activity of incretin hormones leading to -- Increased insulin secretion (in a glucose-dependent manner) -- Decreased glucagon secretion, which reduces hepatic glucose production **Tx:** T2DM **AE:** - pancreatitis - hypersensitivity rxn

Question 36

Drug: **saxagliptin** (Onglyza)

Answer 36

**Class:** DPP-4 inhibitor (dipeptidyl peptidase-4 inhibitor) **MOA:** - Inhibits the enzyme DPP-4, which normally breaks down incretin hormones like: -- GLP-1 (glucagon-like peptide-1) -- GIP (glucose-dependent insulinotropic peptide) - increases levels and prolongs activity of incretin hormones leading to -- Increased insulin secretion (in a glucose-dependent manner) -- Decreased glucagon secretion, which reduces hepatic glucose production **Tx:** T2DM **AE:** - pancreatitis - hypersensitivity rxn

Question 37

Drug: **linagliptin** (Tradjenta)

Answer 37

**Class:** DPP-4 inhibitor (dipeptidyl peptidase-4 inhibitor) **MOA:** - Inhibits the enzyme DPP-4, which normally breaks down incretin hormones like: -- GLP-1 (glucagon-like peptide-1) -- GIP (glucose-dependent insulinotropic peptide) - increases levels and prolongs activity of incretin hormones leading to -- Increased insulin secretion (in a glucose-dependent manner) -- Decreased glucagon secretion, which reduces hepatic glucose production **Tx:** T2DM **AE:** - pancreatitis - hypersensitivity rxn

Question 38

Drug: **canagliflozin** (Invokana)

Answer 38

**Class:** SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitor) **MOA:** - Inhibits SGLT2 in the proximal renal tubules of the kidneys, leading to more glucose excreted in urine -- *SGLT2 is responsible for reabsorbing ~90% of glucose from the urine back into the bloodstream* **Tx:** T2DM **AE:** - hypoglycemia - yeast infections - females/uncircumcised males - UTis - increased urination - dehydration - weight loss - hypotension - if used w/ diuretics **Notes:** - Monitor renal function - **CI w/ GFR less than 30** - Glucosuria (glucose in urine) is an expected finding

Question 39

Drug: **dapagliflozin** (Farxiga)

Answer 39

**Class:** SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitor) **MOA:** - Inhibits SGLT2 in the proximal renal tubules of the kidneys, leading to more glucose excreted in urine -- *SGLT2 is responsible for reabsorbing ~90% of glucose from the urine back into the bloodstream* **Tx:** T2DM **AE:** - hypoglycemia - yeast infections - females/uncircumcised males - UTis - increased urination - dehydration - weight loss - hypotension - if used w/ diuretics **Notes:** - Monitor renal function - **CI w/ GFR less than 30** - Glucosuria (glucose in urine) is an expected finding

Question 40

Drug: **empagliflozin** (Jardiance)

Answer 40

**Class:** SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitor) **MOA:** - Inhibits SGLT2 in the proximal renal tubules of the kidneys, leading to more glucose excreted in urine -- *SGLT2 is responsible for reabsorbing ~90% of glucose from the urine back into the bloodstream* **Tx:** T2DM **AE:** - hypoglycemia - yeast infections - females/uncircumcised males - UTis - increased urination - dehydration - weight loss - hypotension - if used w/ diuretics **Notes:** - Monitor renal function - **CI w/ GFR less than 30** - Glucosuria (glucose in urine) is an expected finding

Question 41

Drug: **ertugliflozin** (Steglatro)

Answer 41

**Class:** SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitor) **MOA:** - Inhibits SGLT2 in the proximal renal tubules of the kidneys, leading to more glucose excreted in urine -- *SGLT2 is responsible for reabsorbing ~90% of glucose from the urine back into the bloodstream* **Tx:** T2DM **AE:** - hypoglycemia - yeast infections - females/uncircumcised males - UTis - increased urination - dehydration - weight loss - hypotension - if used w/ diuretics **Notes:** - Monitor renal function - **CI w/ GFR less than 30** - Glucosuria (glucose in urine) is an expected finding

Question 42

Drug: **exanatide** (Byetta)

Answer 42

**Class:** GLP-1 (Glucagon-like Peptide-1) Receptor Agonist **MOA:** - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Daily** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 43

Drug: **liraglutide** (Victoza)

Answer 43

**Class:** GLP-1 (Glucagon-like Peptide-1) Receptor Agonist **MOA:** - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Daily** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 44

Drug: **exenatide extended-release** (Bydureon)

Answer 44

**Class:** GLP-1 (Glucagon-like Peptide-1) Receptor Agonist **MOA:** - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Weekly** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 45

Drug: **albiglutide** (Tanzeum) | Discontinued in the U.S.

Answer 45

**Class:** GLP-1 (Glucagon-like Peptide-1) Receptor Agonist **MOA:** - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Weekly** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 46

Drug: **dulaglutide** (Trulicity)

Answer 46

**Class:** GLP-1 (Glucagon-like Peptide-1) Receptor Agonist **MOA:** - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Weekly** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 47

Drug: **semaglutide** (Ozempic)

Answer 47

**Class:** GLP-1 (Glucagon-like Peptide-1) Receptor Agonist **MOA:** - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Weekly** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 48

Drug: **tirzepatide** (Mounjaro)

Answer 48

**Class:** *DUAL GIP/GLP-1* Receptor Agonist **MOA:** GIP (gastric inhibitory peptide) - Enhances insulin secretion - Improves beta-cell function GLP-1 (glucagon-like peptide-1) - Enhances glucose-dependent insulin secretion - Suppresses postprandial glucagon secretion - Slows gastric emptying and promotes satiety **Dose:** **Weekly** injectable **Tx:** T2DM **AE:** - hypoglycemia - nausea - associated w/ pancreatitis

Question 49

Hypoglycemia

Answer 49

**Blood Sugar** < 70mg/dL **Treatment:** *CONSCIOUS* * glucose tablets * orange juice * non-diet soda * honey * sugar cube *UNCONSCIOUS* * IV Glucose (preferred) - immediate * Glucagon (SQ, IM, IV) - 20 min to restore consciousness