DM - Therapeutics - Dr. Frye Flashcards
Trials:
IMPROVE-IT
DCCT
IMPROVE-IT - ezetimibe addition to statin therapy may help with recent coronary syndrome
DCCT - Tighter control increases the rate of hypoglycemia
If a patient has normal kidney function but is diabetic, should they be on an ACE or ARB?
No
What are FDA approved drugs to treat diabetic neuropathy? Off-label?
Duloxetine
Pregabalin
Tapentadol
Gabapentin
TCAs
Venlafaxine
Valproate
When is metabolic surgery recommended?
T2DM with BMI of >40 regardless of hyperglycemic control
T2DM with BMI 35-39 with inadequate control despite optimized lifestyle and meds
T2DM with BMI 30-34.9 with poor hyperglycemic control with optimized meds
Term:
Uncontrolled hyperglycemia, metabolic acidosis, increased total body ketone concentration, decreased bicarbonate (<15-18)
DKA
Term:
Severe hyperglycemia, hyperosmolarity, dehydration in absence of ketoacidosis
HHS (hyperosmolar hyperglycemic state)
What can cause DKA?
Missed insulin doses or acute infection
Which type of diabetes is more common in DKA?
Type I
Which type of diabetes is more common in HHS?
Type II. No absolute insulin deficiency, so little ketogenesis.
What are the treatments of DKA and HHS?
Fluids to correct dehydration
Insulin (IV first then SQ) to correct hyperglycemia
Potassium repletion and other interventions as necessary
Where is the line for critically significant hypoglycemia?
<54mg/dL
In hypoglycemia, what symptoms are the first seen? What type are they?
The autonomic/neurogenic symptoms are first seen in hypoglycemia. These are tremors, anxiety, sweating, irritability. These are related to the secretion of epinephrine.
In hypoglycemia, what symptoms are caused by deprivation of glucose to the brain? What are these called?
Confusion, lethargy, loss of consciousness and seizures are neuroglycopenic.
What is the treatment for hypoglycemic unawareness? How does this work?
Less tight A1C control. Increase epinephrine response to low blood sugar. Decrease sensitivity to glucose.
What is the adult dose of glucagon?
1.0mg
How many glucose tabs should be used to treat mild hypoglycemia?
3-4
Why should foods high in protein or fat be avoided when trying to treat hypoglycemia?
Because they will take longer to work.
What is CGM?
Continuous glucose monitoring. Useful in T1DM Can see trends, help people nervous about highs and lows. Cost is an issue. Need robust diabetes education.
How often should A1C be checked in those who are at goal? Not at goal?
In those at goal, check 2 times a year. In those not at goal, check 4 times a year at least.
What is fructosamine?
Measures glycated albumin, but not well standardized.
Indicated for pregnancy and hemoglobinopathies, and those with discordant A1C and CBC results.
What A1C does a 126 mg/dL average glucose reading indicate?
6%
What is the general rule for conversion of A1C to glucose?
A1c-2 x 30
(so an A1C of 7.5: 7.5-2 = 5.5
5.5 x 30 = 150 + 15 = 165
What is a reasonable A1C goal for a healthy adult?
<7%
This is associated with a reduction in microvascular complications
If implemented soon after diagnosis it is also associated with reduction of microvascular complications
What are the glycemic goals for the ADA? A1C Pre-prandial Post-prandial For the AACE?
A1C <7%
Pre-prandial 80-130
Post-prandial <180
A1C <6.5%
Pre-prandial <110
Post-prandial <140
How was the ACCORD trial different than the others, such as UKPDS, ADVANCE, VADT, and DCCT/EDIC?
It found that there was increased mortality with more stringent A1C goals.
Generally, when did trials find microvascular benefits with more stringent A1C goals?
With initial trial and long-term follow-up.
Generally, when did trials find CVD benefits with more stringent A1C goals?
Some CVD benefits seen in follow-up
Generally, when did trials find mortality benefits with more stringent A1C goals?
No change at all, too late.
Why is lower A1C associated with a greater increase of mortality?
Higher A1C is associated with a greater risk of death, but the hypoglycemia associated with lower A1C contributed.
What did the ACCORD trial find about the risks of hypoglycemia?
That hypoglycemia was associated with all sorts of negative outcomes.
What are some potential mechanisms that hypoglycemia can increase CVD risk?
Cardiac arrhythmias
Increased thrombotic tendency
Cvd changes induced by catecholamines
Metformin
a biguanide
MOA - Decreases liver gluconeogenesis and improves insulin sensitivity.
1st line
low cost
weight neutral
No hypoglycemia
Disadvantages: GI intolerance, B12 deficiency, increased risk of lactic acidosis
Continue use unless eGFR is <30. Don’t start metformin if eGFr is less than 45.
Sulfonylureas
MOA - increases insulin secretion by acting in the K channels of beta cells
Low cost
Effective
Generally well-tolerated
Disadvantages: Risk of hypoglycemia, weight gain
1st gen - Achexamide, Tolubutamide, Chloropropamide, Tolazamide
2nd gen - Glimipiride, glipizide, glyburide
Which drug class is SIADH associated with?
Syndrome of Inappropriate Antidiuretic hormone… associated with 1st gen sulfonylureas
Meglitinides
MOA - Increase insulin secretion by binding to the sulfonylurea receptor
Decrease postprandial glucose
Disadvantages: hypoglycemia, weight gain, frequent dosing, only modest efficacy, expensive, CYP 3A4 interactions
Repaglinide, nateglinide
If you miss a meal, skip the dose too
TZDs
MOA - PPAR agonist, which increases sensitivity to insulin
Efficacious
Cheap
Disadvantages: 8-12 weeks for full effect, weight gain, edema (HF CI), bladder cancer, risk of fractures
no hypoglycemia, CVD benefits (PROactive trial), lipid benefits
“glitizones”
Alpha-glucosidase inhibitors
MOA - Delays intestinal carb digestion by inhibiting enzymes in the small intestine
No hypoglycemia, reduces post-prandial hyperglycemia, decreases CVD events
Disadvantages: Flatulence, diarrhea, bloating/gas, modest efficacy
Acarbose, miglitol
LFTs needed for monitoring, initially every 3 months
Avoid use if SCr is >2mg/dL
DPP4 inhibitors
MOA - increases insulin secretion (glucose dependent) and decrease glucagon secretion by inhibiting DPP4, increasing post-prandial incretin (GIP and GLP-1)
No hypoglycemia, well-tolerated, weight neutral
Disadvantages: Expensive, moderate efficacy, pancreatitis, joint pain, HF risk with saxagliptan
Sitagliptan, Saxagliptan, Linagliptan, Alogliptan
What does GLP-1 do?
Decreases appetite Slows gastric emptying Increases insulin secretion Decreases glucagon secretion Increases B-cell proliferation Decreases B-cell apoptosis Decreases glucose production
Which DDP-4 inhibitor does not require renal or hepatic adjustment?
Linagliptan
SGLT2 I’s
MOA - Blocks glucose reabsorption in the kidney, resulting in increased glucose excretion
Advantages: Weight loss, low hypoglycemia risk, modest BP lowering, CVD benefit (empagliflozin)
Disadvantages: All CI w/ renal dysfunction, UTIs, genital mycotic infections, euglycemic ketoacidosis, modest efficacy, high cost, bone fracture with canagliflozin
Canagliflozin, dapagliflozin, empagliflozin
GLP-1 agonists
MOA - Increase insulin secretion, decrease glucagon secretion, slows gastric emptying, increases satiety
Efficacious, no hypoglycemia, weight reduction, improved beta-cell mass, Cvd benefit with liraglutide (LEADER trial)
Disadvantages: GI side effects, increased pancreatitis risk, high cost, no long term safety data
Black box warnings for all but exanitide for thyroid C cell tumors
Exanitide, liraglutide, albiglutide, dulaglutide
Amylin analog
MOA - slows gastric emptying, decreases glucagon secretion, increases satiety
Adjunct to mealtime insulin only, moderately efficacious, decreases postprandial glucose, weight loss
Disadvantages: GI effects, no long term safety, frequent dosing, hypoglycemia potential with insulin use, high cost.
(Decrease insulin dose by 50% when taking)
Insulin
MOA - facilitates cellular uptake of glucose, and reduces hepatic glucose production
Universally effective, unlimited efficacy, decreases microvascular complications
Disadvantages: weight gain, hypoglycemia, injectable, SMBG required, cost
Human insulin vs insulin analogs:
Human: identical to endogenous insulin. Protamine and zinc can be added to create NPH, which has delayed peak and duration.
Insulin analogs are created by genetic engineering, which alters pharmacokinetics.
When is U-500 insulin useful?
For when daily injections total 200 units or more
What are the rapid-acting insulins?
Humalog
Novolog
Apidra
Take immediately before a meal
What are the short-acting insulins?
Regular (R)
Novolin R
HUmulin R
Take 30 minutes before a meal
What are the intermediate-acting insulins?
NPH
Novolin N
Humulin N
(The only cloudy insulins)
What are the long-acting insulins?
detimir
glargine
degludec
What is Afrezza?
Inhaled insulin.
Administer before meals.
Warnings of acute bronchospasm in patients with chronic lung disease
What combos of split-mixed insulins can you use?
NPH and glassine, aspart, or lispro
NPH and regular
NO glargine, deter, or degludec
