Type 2 DM Flashcards
Discuss the pathophysiology of T2DM
- Results from defective insulin secretion followed by loss of B-cell mass in response to increased demand as a result of insulin resistance
- Loss of pancreatic cells is progressive; however, insulin secretion is usually sufficient to prevent ketosis under basal conditions
- Mechanism of B-cell loss is unknown but programmed cell death in response to genetic and environmental factors demonstrated in animals
What is the A1c goal for T2 diabetics?
<7% or as low as can be achieved safely
What is first line treatment for T2DM?
Metformin if tolerated
How long does it take to see results from each class of medications?
Metformin, insulin secretagogues, DPP-IV inhibiors and glucagon-like-peptide-1 analogs: within days to weeks
Thiazolidinedione: several weeks to months
When is it necessary to start combo therapy in T2 diabetics?
May be needed at the time of diagnosis to achieve A1c and glucose targets in patients presenting with significant hyperglycemia and will likely be needed as B-cell function deteriorates over time
When is it necessary to start insulin therapy in T2 diabetics?
Considered in patients presenting in DKA or with very high glucose levels (A1c >10%)
Insulin secretatagogues (sulfonylureas): give examples of medications in this class
Glyburide
Glipizide
Glimepiride
Gliclazide
MOA of Insulin secretatagogues (sulfonylureas)
Increase insulin secretion by binding specific receptors in B-cells
What is the frequency of Insulin secretatagogues (sulfonylureas) dosing?
30-60 mins before food and should never be administered to fasting patients
Which of the SFUs should be avoided in patients with renal failure and why?
Glyburide because it has an active metabolite with significant renal excretion
Which of the SFU’s has the longest duration of action?
Glimepiride (administered once per day)
Which populations tend to do well with SFUs?
Newly diagnosed T2DM with mild-moderate fasting hyperglycemia
List the most common adverse effects of SFUs
Hypoglycemia (MC with glyburide)
Weight gain
Biguanide
List the only medication in this class
Metformin
What is the MOA of the Biguanide
Inhibits hepatic glucose output and stimulates glucose uptake by peripheral tissues
How is the Biguanide dosed?
Taken with food beginning with a single 500 or 850mg tablet, and the dose is increased every few days to weeks until optimal glycemic effect is achieved or 2,000mg/d is reached
What are the most common side effects of the Biguanide?
GI sx
What is the most serious adverse effect of the Biguanide? What are risk factors for this condition?
Lactic acidosis (incidence of 3/100,000 patient-years and significant mortality rate)
RF: renal dysfunction, hypovolemia, tissue hypoxia, infection, alcoholism, cardiopulmonary disease
What are contraindications for the Biguanides?
- Serum creatinine level of >1.5 mg/dL in men and >1.4 mg/dL in women
- eGFR of <60 mL/min
- Other situations: cardiogenic or septic shock, CHF requiring pharm therapy, severe liver dx, pulm insufficiency with hypoxemia, severe tissue hypo perfusion
How do you dose Metformin if the patient needs radioactive dye for imaging?
Discontinued at time of contrast procedure and not restarted for 48 hours
Thiazolidinediones
What medication is in this class?
Pioglitazone
What is the MOA of TZDs?
Increase insulin sensitivity in muscle, adipose tissue, and liver
How are TZDs dosed?
- Initial dose is 15 or 30mg PO daily taken with or without food and can be increased after several weeks to 45mg PO daily
- Max dose approved with insulin is 30mg daily
What other insulin therapies can TZDs be combined with?
SFU, metformin, sitagliptin, exanatide, insulin
What is the most common adverse effect of TZDs?
Edema (ranging from none to mild peripheral edema)
Which populations of patients should not receive TZDs?
Patients with compromised cardiac function
What do you need to monitor (lab wise) with this TZDs?
Periodic monitoring of liver function (LFTs): risk of drug induced hepatotoxicity
What hematologic effects does TZDs have on the body?
Mild decrements in hemoglobin and/or pancytopenia due to an increased plasma volume but also subclinical bone marrow suppression
What are the MSK risks with TZDs?
Increase the risk of fracture in women, particularly smaller bones due to inhibition of osteoblast activity
What do you need to advise women of child bearing age who are taking this medication?
Resumption of ovulation may occur during TZD therapy in premenopausal women with anovulatory cycles, so contraceptive practice should be reviews to prevent unintended pregnancy
DPP-IV inhibitors
Give examples of medications in this class
Sitagliptin
Vildagliptin
Saxaglitpin
Linagliptin
What is the MOA of DPP-IV inhibitors?
Inhibitors of DPP-IV, the enzyme that breaks down endogenous GLP, which is an incretin secreted from the intestinal L cells. Increased levels of GLP reduce BG concentration by inhibiting glucagon secretion from pancreatic alpha cells and stimulating insulin secretion
How is sitagliptin dosed? What populations need to avoid this medication? What are ADRs?
Once daily at 100mg
Elimination pathway is predominately renal so dose reduction recommended in patients with reduced renal function (50mg if eGFR <50 or 25mg if <30)
How is saxagliptan dosed?
What are the main SE?
Once daily in doses of 2.5 or 5 mg with lower dose used in patients with creatinine clearance <50mL/min
SE: uticaria and facial edema
How is linagliptan dosed?
Why is this medication better for patients with renal disease?
Once daily 5mg
Due to its fecal route of excretion
GLP agonists/mimetics
Give examples of medications in this class
Exenatide
Liraglutide
What is the MOA of GLP agonists?
Structurally similar to endogenous GLP1 but resist breakdown by DPP enzymes à longer half-life and reach higher blood and tissue levels
How is exanatide dosed?
SC injection in doses of 5 or 10 micrograms twice daily before meals
How much can exanatide lower an A1c by?
0.6% to 1.2%
What are ADRs of exanatide?
Pancreatitis and acute renal failure
How is liraglutide dosed?
SC injection once daily at any time in doses of 0.6, 1.2 or 1.8 mg
What are the main SE of liraglutide?
N/V, dizziness, and HA
What are the two main ADR found in rodents in liraglutide?
Increased calcitonin levels and medullary thyroid cancer
When is insulin therapy indicated in a T2DM patient?
- Patients whom oral or injectable agents have failed to achieve or sustain glycemic control
- Metabolic decompensation: DKA and nonketotic hyperosmolar crisis
- New diagnosed pt with severe hyperglycemia
- Pregnancy and other situations in which oral agents are contraindicated
List common combination therapies
What is the most common?
SFU plus metformin
What is a good regimen for combo therapy if weight loss is the goal?
Metformin plus DPP-IV inhibitor or GLP analog
Why are TZDs avoided with insulin?
Higher incidence of CHF exacerbations
