N596 Exam 4 Study Guide
How is it that insulin secretion is triggered? - Answer Glucose enters beta cells of
pancreas, then K+/ATP channel closes, and calcium enters the cell. Then insulin
secretion occurs.
When the K+/ATP channel is closed, insulin - Answer is secreted. The reverse is also
true: when the K+/ATP channel is open, insulin is low.
Main 3 cell targets for insulin - Answer 1. Skeletal muscle
2. Adipose tissue
3. Liver cells
Though metformin is usually first line for insulin resistance, when would that not be the
best choice? - Answer Established ASCVD or at high risk for it, stage 3 chronic kidney
disease, or heart failure with reduced ejection fraction > want to instead use long-acting
GLP1-RA or SGLT2i
Biguanide Class: Metformin MOA - Answer *Inhibits hepatic glucose production*,
improves glucose uptake at tissues, enhances insulin sensitivity, decreases glucose
absorption in GI tract.
Adverse effects metformin - Answer NV, diarrhea, bloating, cramping, flatulence,
anorexia
BBW for lactic acidosis risk, especially if pt has renal/hepatic disease
Cautions with metformin - Answer -Renal impairment
-Pt at risk for lactic acidosis (>65, contrast dyes, excess alcohol use)
-Low B12-related neuropathy
How long for metformin to reach full effects? - Answer 2 weeks
What is GLP1 and how is it regulated? - Answer It is an incretin hormone that is
produced in the intestine and brain after food intake. It stimulates insulin secretion and
inhibits glucagon secretion, slows gastric emptying (induces satiety).
Incretin's relation to T2DM - Answer In T2DM, incretin effects are impaired.
DPP4 - Answer On surface of most cells and degrades peptides and GLP1.
GLP1 Agonist med examples - Answer "Glutides"
Liraglutide (Victoza, Saxenda)
Also, exenatide (Byetta)
,GLP1 agonist: liraglutide clinical uses - Answer -Weight loss
-Decrease A1C by 0.9-1.1%
-Decrease risk of major CV events in adults with ASCVD
-Renal protective
Adverse effects GLP1 agonist liraglutide - Answer NV, diarrhea/constipation, dyspepsia,
pain
Pancreatitis, acute kidney injury, gallbladder disease, medullary thyroid carcinoma
BBW for thyroid c-cell tumor
GLP1 agonists mechanism of delivery - Answer Injection because they are peptides.
Some injected daily, some weekly. Expensive.
DPP-4 inhibitor examples - Answer "Gliptin"
Sitagliptin (Onglyza)
MOA sitagliptan - Answer Inhibit DPP-4, which is an enzyme that inactivates incretins.
This increases levels of GLP1, increases glucose-dependent insulin secretion from beta
cells, and decreases glucagon secretion from alpha cells.
DPP-4 inhibitor drugs effect on weight - Answer Neutral towards weight
Adverse effects DPP-4 inhibitors - Answer -HA
-Nasopharyngitis, URI
-Arthralgia
-Anaphylaxis, angioedema
-Blistering skin conditions
-Pancreatitis
-Heart failure hospitalization risk with saxagliptin and alogliptin especially
DPP-4 inhibitors PK highlights - Answer -CYP3A4 metabolism with significant renal
excretion, requiring dose adjustment for renal impairment
Which 2 classes of anti-diabetic drugs should not be given together? - Answer GLP-1
agonists and DPP4 inhibitors (overlapping mechanisms)
SGLT-2 inhibitor examples - Answer "Gliflozin"
Canagliflozin, dapagliflozin, etc
,SGLT-2 inhibitor canagliflozin MOA - Answer Inhibits SGLT2 (which usually reabsorbs
90% of glucose) in kidney. This increases excretion of glucose in urine. Also increases
excretion of sodium in urine.
SGLT-2 inhibitor clinical uses - Answer -Reduce CV events in diabetics with CVD
-Reduce risk of end-stage kidney disease, CV death, HF hospitalization
-Also decreases BP
Adverse effects of SGLT-2 inhibitors such as canagliflozin - Answer -Infections (fungal
genital infections, UTIs)
-Thirst, dehydration
-HOTN, syncope
-Hyperkalemia
-AKI
-Ketoacidosis
-Bone fractures
-Nec fac of perineum
Thiazolidinedione examples - Answer "Glitazone"
Pioglitazone (Actos)
Thiazolidinediones such as pioglitazone MOA - Answer PPAR gamma agonist, affecting
transcription of genes involved in glucose and lipid metabolism. Improves insulin
receptor sensitivity and glucose utilization in adipose and muscle. *Dependent on
presence of endogenous insulin.*
Clinical uses of thiazolidinediones like pioglitazone - Answer -Can be monotherapy for
insulin resistance or a combo with sulfonylurea/metformin/insulin
-Can cause weight gain
-Decreases A1C by 0.5-1.4%
Adverse effects of thiazolidinediones like pioglitazone - Answer -Edema, heart failure
-Increase LFTs, liver failure
-Macular edema
-Bone fracture
-Bladder cancer
, What is the BBW for thiazolidinediones like pioglitazone? - Answer Can cause or
exacerbate heart failure
PK highlights of thiazolidediones - Answer -Metabolized by CYP2C8 to active and
inactive metabolites
-Females have higher levels of them
-Worsen adverse effects of insulin/sulfonylureas if dual administration
Sulfonylurea examples - Answer 1st gen- chlorpropamide
2nd gen- glimepiride, glipizide, glyburide
2nd generation preferred as 1st gen have increased risk for rash/allergy
Sulfonylureas like glipizide MOA - Answer Stimulate endogenous insulin release by
inhibiting K+/ATP channel in beta cells of pancreas and promoting depolarization which
causes the insulin to be released.
Adverse effects of sulfonylureas like glipizide - Answer -*Hypoglycemia, which can be
severe*
-Dizziness
-HA
-GI effects
-*Weight gain*
-Risk for hemolytic anemia if pt has G6PD deficiency (may consider genetic testing)
Lose their efficacy over time
Insulin MOA at each target tissue - Answer Liver: inhibit glycogenolysis,
gluconeogenesis. Promote glycogen synthesis. Increases TG and VLDL formation
Muscle: Increased glucose transport with GLUT4, increased protein synthesis,
promotes glycogen synthesis
Adipose: Increased glucose transport with GLUT4, stimulates lipogenesis, inhibits
lipolysis, inhibits FFA release.
List the insulins from short to long acting - Answer Very rapid: Aspart (Fiasp), lispro
(Lyumjev)
Rapid: Lispro (humalog, admelog), aspart (novolog), glulisine (apidra), inhaled insulin
Short: Regular (humulin R, novolin R)
Intermediate: NPH (humulin N, novolin N)
How is it that insulin secretion is triggered? - Answer Glucose enters beta cells of
pancreas, then K+/ATP channel closes, and calcium enters the cell. Then insulin
secretion occurs.
When the K+/ATP channel is closed, insulin - Answer is secreted. The reverse is also
true: when the K+/ATP channel is open, insulin is low.
Main 3 cell targets for insulin - Answer 1. Skeletal muscle
2. Adipose tissue
3. Liver cells
Though metformin is usually first line for insulin resistance, when would that not be the
best choice? - Answer Established ASCVD or at high risk for it, stage 3 chronic kidney
disease, or heart failure with reduced ejection fraction > want to instead use long-acting
GLP1-RA or SGLT2i
Biguanide Class: Metformin MOA - Answer *Inhibits hepatic glucose production*,
improves glucose uptake at tissues, enhances insulin sensitivity, decreases glucose
absorption in GI tract.
Adverse effects metformin - Answer NV, diarrhea, bloating, cramping, flatulence,
anorexia
BBW for lactic acidosis risk, especially if pt has renal/hepatic disease
Cautions with metformin - Answer -Renal impairment
-Pt at risk for lactic acidosis (>65, contrast dyes, excess alcohol use)
-Low B12-related neuropathy
How long for metformin to reach full effects? - Answer 2 weeks
What is GLP1 and how is it regulated? - Answer It is an incretin hormone that is
produced in the intestine and brain after food intake. It stimulates insulin secretion and
inhibits glucagon secretion, slows gastric emptying (induces satiety).
Incretin's relation to T2DM - Answer In T2DM, incretin effects are impaired.
DPP4 - Answer On surface of most cells and degrades peptides and GLP1.
GLP1 Agonist med examples - Answer "Glutides"
Liraglutide (Victoza, Saxenda)
Also, exenatide (Byetta)
,GLP1 agonist: liraglutide clinical uses - Answer -Weight loss
-Decrease A1C by 0.9-1.1%
-Decrease risk of major CV events in adults with ASCVD
-Renal protective
Adverse effects GLP1 agonist liraglutide - Answer NV, diarrhea/constipation, dyspepsia,
pain
Pancreatitis, acute kidney injury, gallbladder disease, medullary thyroid carcinoma
BBW for thyroid c-cell tumor
GLP1 agonists mechanism of delivery - Answer Injection because they are peptides.
Some injected daily, some weekly. Expensive.
DPP-4 inhibitor examples - Answer "Gliptin"
Sitagliptin (Onglyza)
MOA sitagliptan - Answer Inhibit DPP-4, which is an enzyme that inactivates incretins.
This increases levels of GLP1, increases glucose-dependent insulin secretion from beta
cells, and decreases glucagon secretion from alpha cells.
DPP-4 inhibitor drugs effect on weight - Answer Neutral towards weight
Adverse effects DPP-4 inhibitors - Answer -HA
-Nasopharyngitis, URI
-Arthralgia
-Anaphylaxis, angioedema
-Blistering skin conditions
-Pancreatitis
-Heart failure hospitalization risk with saxagliptin and alogliptin especially
DPP-4 inhibitors PK highlights - Answer -CYP3A4 metabolism with significant renal
excretion, requiring dose adjustment for renal impairment
Which 2 classes of anti-diabetic drugs should not be given together? - Answer GLP-1
agonists and DPP4 inhibitors (overlapping mechanisms)
SGLT-2 inhibitor examples - Answer "Gliflozin"
Canagliflozin, dapagliflozin, etc
,SGLT-2 inhibitor canagliflozin MOA - Answer Inhibits SGLT2 (which usually reabsorbs
90% of glucose) in kidney. This increases excretion of glucose in urine. Also increases
excretion of sodium in urine.
SGLT-2 inhibitor clinical uses - Answer -Reduce CV events in diabetics with CVD
-Reduce risk of end-stage kidney disease, CV death, HF hospitalization
-Also decreases BP
Adverse effects of SGLT-2 inhibitors such as canagliflozin - Answer -Infections (fungal
genital infections, UTIs)
-Thirst, dehydration
-HOTN, syncope
-Hyperkalemia
-AKI
-Ketoacidosis
-Bone fractures
-Nec fac of perineum
Thiazolidinedione examples - Answer "Glitazone"
Pioglitazone (Actos)
Thiazolidinediones such as pioglitazone MOA - Answer PPAR gamma agonist, affecting
transcription of genes involved in glucose and lipid metabolism. Improves insulin
receptor sensitivity and glucose utilization in adipose and muscle. *Dependent on
presence of endogenous insulin.*
Clinical uses of thiazolidinediones like pioglitazone - Answer -Can be monotherapy for
insulin resistance or a combo with sulfonylurea/metformin/insulin
-Can cause weight gain
-Decreases A1C by 0.5-1.4%
Adverse effects of thiazolidinediones like pioglitazone - Answer -Edema, heart failure
-Increase LFTs, liver failure
-Macular edema
-Bone fracture
-Bladder cancer
, What is the BBW for thiazolidinediones like pioglitazone? - Answer Can cause or
exacerbate heart failure
PK highlights of thiazolidediones - Answer -Metabolized by CYP2C8 to active and
inactive metabolites
-Females have higher levels of them
-Worsen adverse effects of insulin/sulfonylureas if dual administration
Sulfonylurea examples - Answer 1st gen- chlorpropamide
2nd gen- glimepiride, glipizide, glyburide
2nd generation preferred as 1st gen have increased risk for rash/allergy
Sulfonylureas like glipizide MOA - Answer Stimulate endogenous insulin release by
inhibiting K+/ATP channel in beta cells of pancreas and promoting depolarization which
causes the insulin to be released.
Adverse effects of sulfonylureas like glipizide - Answer -*Hypoglycemia, which can be
severe*
-Dizziness
-HA
-GI effects
-*Weight gain*
-Risk for hemolytic anemia if pt has G6PD deficiency (may consider genetic testing)
Lose their efficacy over time
Insulin MOA at each target tissue - Answer Liver: inhibit glycogenolysis,
gluconeogenesis. Promote glycogen synthesis. Increases TG and VLDL formation
Muscle: Increased glucose transport with GLUT4, increased protein synthesis,
promotes glycogen synthesis
Adipose: Increased glucose transport with GLUT4, stimulates lipogenesis, inhibits
lipolysis, inhibits FFA release.
List the insulins from short to long acting - Answer Very rapid: Aspart (Fiasp), lispro
(Lyumjev)
Rapid: Lispro (humalog, admelog), aspart (novolog), glulisine (apidra), inhaled insulin
Short: Regular (humulin R, novolin R)
Intermediate: NPH (humulin N, novolin N)
