Diabetes Therapeutics Flashcards Preview

Pharmacy School 2016-17 > Diabetes Therapeutics > Flashcards

Flashcards in Diabetes Therapeutics Deck (97):

When we consider insulin in a new diagnosis (ADA)

Symptomatic and/or have an AIC of 10% or more and/or CBGs 300 of higher

Insulin should always be considered if A1C is around 9-10% (this doesn't mean the patient will be on it forever!)


Guideline recommendations for patient with long-standing suboptimally controlled T2DM and ASCVD

Empagliflozin or liraglutide (shown to reduce CV and all-cause mortality in combo with standard care)


Considerations for treating diabetes in older adults

Reduced life expectancy, higher CVD burden, reduced GFR, at risk for adverse events from polypharmacy, more likely to be compromised from hypoglycemia

Consider less ambitious targets (<7.5-8% if tighter targets not easily achieved)


Recommendations for reasonable A1C treatment goals in older adults based on level of health

Healthy (<7.5%)
Comorbidities (<8%)
Very complex/poor health (<8.5%)

*the key is to individualize


Considerations in treating a diabetic with renal disease

Increased risk of hypoglycemia

Avoid glyburide, use other insulin secretagogues cautiously

Reduce metformin dose when eGFR <45 and avoid if less than 30

Most DPP4 inhibitors require dose adjustment

avoid exenatide if CrCl <30 ml/min

avoid SGLT2 inhibitors for eGFR <45-60 (agent specific)


Which agents have minimal hypoglycemia risk?

Thiazolidinediones, DPP4s, SGLT2s and GLP-1s

Insulin and sulfonylureas should be avoided


Considerations for those with coronary disease

Avoid hypoglycemia

Empagliflozin reduces CV events in high-risk patients

Liraglutide reduces CV events in high-risk patients


Considerations for those with heart failure

Metformin is ok unless HF is severe or unstable

Avoid thiazolidinediones

Warning with DPP4i saxagliptin

Potential benefit with SGLT2 inhibitors based on diuretic effect

Liraglutide reduced CV outcomes in high-risk patients


EMPA-REG outcome(s)

Reduction in CV death, death from any cause and HF hospitalizations (with Empagliflozin compared with placebo)


LEADER outcome(s)

Reduction in CV death, death from any cause and microvascular outcomes

No reduction in HF hospitalizations, nonfatal MI or nonfatal stroke



The time to effect was delayed in the LEADER trial (Liraglutide, > 12-18 months) compared with EMPA-REG (< 3 months)


Considerations for those with liver dysfunction

Most drugs not tested in advanced liver disease

Pioglitazone and metformin may be beneficial for NAFLD but should be avoided in active or advanced liver disease

Insulin best option for patients with advanced disease


Considerations for those with obesity

Obesity can contribute to insulin resistance

Preference for or weight neutral or weight loss agents

Diet, physical activity and behavior changes (goal at least 5% weight loss)

Consider weight loss medications as adjunct to lifestyle

Consider or recommend metabolic surgery (if BMI > 30)


Which medications are ideal if patient wants to avoid weight gain?

DPP4, SGLT2 and GLP-1 agonist, metformin

Sulfonylureas, thiazolidinediones and insulin should be avoided


What medications are ideal if the patient wants to minimize cost?

Sulfonylureas, thiazoidinediones, metformin

DPP4, SGLT2, GLP1 and Insulin should all be avoided (except for insulin N/R 70/30 which is cheap at walmart)


Initial daily dose of insulin for T1DM

0.3-0.5 units/kg/day


Diabetes in pregnancy

Metformin + insulin preferred (glyburide now inferior)

Levemir, Humalog and Novolog (category B); Lantus (category C)

Tighter glycemic control indicated (especially for those with pre-existing T2/T1DM): bedtime 60-99, postprandial 100-129, A1C <6%


General guidelines for initiating/titrating insulin in T2DM

Start 10 U/day or 0.1-0.2 U/kg/day

Adjust 10-15% or 2-4 units once or twice weekly to reach FBG target

For hypo, do the opposite of the increase dose adjustment


Initiating basal insulin algorithm

Bedtime NPH, detemir glargine (start with 10 units or 0.1-0.2 U/kg and increase weekly/bi-weekly by 10-15% or 2-4 units)

If hypoglycemia then decrease by 10-20% or 4 units

If A1C not controlled after FBG reached and basal dose >0.5 U/kg/day add post-prandial insulin or consider GLP-1 agonist


Dosing consideration for insulin detemir

Dose dependent duration of action (6 hours at low doses-23 hours at high doses)

Appropriate to start with qd dosing and split later on if insulin appears to be wearing off


Dosing considerations for insulin degludenc

Can be injected at variable times so could be advantageous in patients with poor adherence


When is it time to consider adding on bolus or meal-time insulin?

When fasting glucose is under control but A1C remains greater than goal after 3-6 months of basal insulin

If titration of basal insulin leads to nocturnal hypoglycemia

When basal doses exceed 0.5 U/kg/day


General dosing of adding mealtime insulin before patients largest meal

Start with 4, adjust by 2 units every 3 days until CBG within range


What is an insulin sliding scale

Catching up

Uses a correction factor which refers to use of additional short or rapid-acting insulin in addition to scheduled insulin doses


Calculating ISF

1500 for regular/TDD
1800 for rapid/TDD
Target BG - Actual BG/ISF = # of units needed to correct

Usually want to skip or decrease correction dose by 1/2 at bedtime to avoid hypoglycemia


Insulin Carbohydrate ratio

In general, approximately 1 unit per 10-15 g CHO

500/TDD = grams of carbs covered


Lab values that define normal range (not diabetic)

FPG 70-99
2-hour Plasma Glucose 100-139
A1C 4.5-5.6%


Lab values that define pre-diabetes

FPG 100-125
2-hour Plasma Glucose 140-199
A1C 5.6-6.4%


Lab values that define diabetes

FPG 126 or higher
2-hour Plasma glucose 200 or higher
A1C 6.5% or higher

Diagnosis should be confirmed by repeat testing unless RBG 200 or more with overt symptoms of hyperglycemia


Gestational diabetes risk factors

Ethnicity (African-American, Native American, Asian), obesity, age over 25, family history of T2DM, signs of insulin resistance (PCOS, lipids), maternal history of gestational diabetes, prior delivery of baby exceeding 9 pounds

*screen all with risk factors or at the 24-28 week mark


Frequency all adults should be tested for T2DM

All adults 45 or over should be tested every 3 years (if normal)


How often is urinary albumin excretion assessed?



Vaccine recommendations in diabetics

Influenza (annually)

Pneumococcal (PPSV23 x 1; PPSV23 & PCV12 for those 65 or older)

HepB vaccine series recommended for adults 19-59


General blood pressure goal in diabetics

under 140/90

130/80 could be used in patients that can handle a stricter goal


Lipid management in diabetes

Statin therapy often recommended

In adults not taking a statin, check lipid profile at diagnosis and then at least every 5 years

When taking a statin, lipids should be checked periodically to assess response to therapy and adherence


Therapy recommendation for patient (age >40) with ASCVD who cannot tolerate high-intensity statin therapy

Moderate intensity statin + ezetimibe

Also used in those with ACS and LDL of 50 or more (IMPROVE-IT trial)


Which STATINs are high-intensity? What are their dosage strengths?

Rosuvastatin 20-40mg
Atorvastatin 40-80mg


Recommended anti-platelet therapy in diabetes

Low-dose aspirin (75-162 mg/day) indicated for primary prevention in those with increased CV risk (10-year risk >10%) - includes most men/women 50+ years of age with at least 1 additional risk factor

Aspirin not recommended for those with 10-year risk <5% (between 5-10%, use clinical judgement)

Use aspirin as a secondary prevention in those with diabetes and a history of ASCVD (clopidogrel 75mg if aspirin allergy)

Dual therapy acceptable up to 1 year after ACS


Nephropathy treatment recommendations (general)

Assess urinary albumin annually in those with T2DM and in those with T1DM for 5 or more years

Optimize glycemic control and BP

ACEi or ARB recommended for all with abnormal albuminuria (>29) or eGFR <60


Eye exams in T1/T2DM

Done in those with T1 within 5 years of diagnosis, shortly after diagnosis in T2

If no retinopathy, repeat every 2 years; if present, every year


Foot exams in diabetes

screen for diabetic peripheral neuropathy annually

Feet inspection at every visit


Agents for diabetic neuropathy

FDA approved (Duloxetine, Pregabalin, Tapentadol)

Off-label (TCAs - amitriptyline, nortriptyline; Gabapentin, Valproate)


Minimum recommendation for exercise in diabetic patients

150 minutes or more of moderate physical activity a week (or 75 minutes of vigorous exercise)

Recommended to perform resistance training at least twice per week

Prolonged sitting should be interrupted every 30 minutes for blood glucose benefits


When should metabolic surgery be recommended?

BMI 40+ (regardless of glycemic control)

BMI 35-39.9 (glycemic control not adequate)

BMI 30-34.9 (poor glycemic control)


Medications/drug abuse that could result in DKA

Cocaine, Meth

Clozapine, olanzapine, steroids


Caloric intake recommendation during sick day to avoid DKA

45 g carbs every 4 hours and drink plenty of fluid


Signs/symptoms of DKA

NV, thirst, polyuria, abdominal pain, vision blurring

Tachycardia, hypotension, dehydration, warm dry skin, Kussmail respiration, fruity breath, mental status change


Describe HHS

Hyperglycemic Hyperosmolar State

Usually seen in older individuals with predisposing factors

No absolute insulin deficiency so little ketogenesis (hyperglycemia usually worse but little acidosis)

Much more dehydration secondary to worsening hyperglycemia


Blood glucose level for clinically significant hypoglycemia

< 54 mg/dL


Glucose utilization is ___________ during exercise; insulin sensitivity is __________ during/following exercise




Alcohol impairs __________



What hormones/molecules are released when BG drops to 60 mg/dL or lower


Growth hormone and corisol (both antagonize insulin)


Contributing factors to hypoglycemia unawareness

Often occurs in those with frequent hypoglycemia

Reduction in epinephrine response to low BG, increased expression of glucose transporters in brain (GLUT1, GLUT3), suppression of autonomic responses secondary to cortisol


Treatment of hypoglycemia

MILD (rule of 15) - ingest 15 grams of rapid acting carb, re-check in 15 minutes (5 lifesavers, 3-4 glucose tabs, 4 oz juice/soda, 8oz milk, avoid high-fat foods, follow with a snack or small meal within 1-2 hours)

SEVERE - glucagon kit (adults = 1.0 mg, children <5 = 0.5 mg, infants = 0.25 mg)


Fructosamine levels

Measure of glycated albumin, reflecting the average glucose over 2-3 weeks

Indicated for pregnancy and hemoglobinopathies; could be useful in patient with discordant A1C and CBGs

Not well standardized and not to be used for diagnosis


Benefit of A1C goal

Lowering below or around 7% associated with microvascular complication reduction; if implemented soon after diagnosis, has been reduction in macrovascular disease


Factors leading to less stringent A1C goals?

High risk of hypoglycemia or AEs, long-standing disease duration, short life-expectancy, many comorbidities, severe established vascular complications, less motivated patient, limited resources/support


Benefit of intensive therapy in diabetes (summary of major clinical trials)

Decrease in microvascular complications (long and short term)

CVD reduction long-term, not short

Relatively no change in mortality (some increase in mortality - ACCORD trial)


How does hypoglycemia increase CVD risk

Cardiac arrhythmias due to abnormal cardiac repolarization

Increased thrombotic tendency/decreased thrombolysis

CV changes induced by catecholamines (increased HR, silent myocardial ischemia, angina/MI)


Metformin advantages

A1C reduction by 1-2%

Decrease in micro and macro-vascular complications (UKPDS)

Weight neutral



Metformin contraindications

eGFR <30, hepatic disease, excessive alcohol intake, 80+ y.o., acute illness/major surgery/infection, hypoxic states, dehydration and iodinated constrast media


Lactic acidosis signs/symptoms

SOB, muscle aches, weakness, ataxia, altered mental status, palpitations, slurred speech, tachypnea


Metformin recommendations based on eGFR

60+ (continue)
45-59 (monitoring every 3-6 months)
30-44 (prescribe with caution, use lower dose such as 50% max, monitor renal function every 3 months, avoid starting in new patients)


Sulfonylurea advantages

Decrease A1C by 1-1.5%

Low-cost generics


Decease microvascular complications


Sulfonylurea disadvantages

Hypoglycemia (mostly in elderly) - greater risk with glyburide due to active metabolites (medicare won't pay for glyburide as result)

Weight gain (1-3 kg)

Low durability

*glimepiride is the only other 2nd generation with active metabolites but they have minimal activity


Glyburide dosing consideration

If CrCl <50 avoid use


Sulfonylurea dosing consideration (general)

In general, the max effective dose is about 1/2 of the max approved dose

Glipizide 20mg/day (ER 10mg/day)
Glimepiride 4mg/day
Glyburide 10mg/day


Rare ADRs with sulfonylureas

Syndrome of inappropriate Antidiuretic Hormone (SIADH; Chlorpropamide and tolbutamide may increase release of ADH)

Disulfiram reactions (chlorpropamide)


Hemolytic anemia


Meglitinides disadvantages

Frequent dosing schedule

Decrease A1C only by 0.5-1%

Both agents cleared by liver and metabolized by CYP3A4 (Nateglinide also by 2C9 and inhibits 2C9) - interaction with gemfibrozil, itraconazole (and other 3A4 inhibitors/inducers)


If patient skips a meal, the (sulfonylurea/meglitinide) should be skipped



Thiazolidinediones advantages

No hypolgycemia, durable, increase HDL, lower TG, lower CVD


Thiazolidinediones disadvantages

Weight gain, edema/HF, bladder cancer, increased risk of fractures, decrease A1C only by 0.5-1.4%


Alpha-glucosidase inhibitors disadvantages

Modest efficacy (decrease A1C 0.5-0.9%)


Alpha-glucosidase inhibitors contraindications

IBD, intestinal obstruction, GI disorders

Cirrhosis of liver

Avoid use if Scr > 2mg/dl


What to use if patient has low blood sugary while taking alpha-glucosidase inhibitor

Sucrose won't work, must use glucose


DPP4 inhibitors MOA

Increase insulin secretion, decrease glucagon secretion by inhibiting DPP4 (which increases postprandial GLP-1,GIP)


DPP-4 Inhibitor Disadvantages

Only decrease A1C by 0.5-0.8%

High cost

Increased risk of pancreatitis (counsel on nausea, vomiting, anorexia and persistent abdominal pain)

FDA warning for joint pain (went away with removal of agent)

HF risk with saxagliptin and alogliptin

All require renal adjustment (except Linagliptin)


SGLT2 inhibitors disadvantages

4-7 fold increase in genital mycotic infections, increased risk of UTIs

Increased risk of euglycemic ketoacidosis

Increased urination, fluid loss

Hyperkalemia/serum creatinine bump

Relatively modest efficacy (decreases A1c by 0.5-1%)

High cost


FDA safety alert for Canagliflozin

Bone fractures can occur more frequently (as early as 12 weeks after start)



Bile acid sequestrant (decreases hepatic glucose production, increases incretin levels)

Decreases A1C by 0.3-0.4%

GI side effects, high cost



Ergot derived dopamine agonist (modulates hypothalamic regulation of metabolism, increases insulin sensitivity)

Decreases A1C by 0.4-0.5%

GI side effects, dizziness, nausea, fatigue, rhinitis


GLP-1 Agonists advantages

Decrease A1C by 0.5-1.5%, no hypoglycemia, weight reduction through increased satiety, potential beta-cell proliferation/increase in function, CVD benefit (liraglutide)


GLP-1 agonists disadvantages

GI side effects, increased risk of pancreatitis, high cost

BLACK BOX WARNING (all but byetta) for thyroid-C cell tumors


Special considerations for GLP-1 agonist formulations

Albiglutide (requires mixing)

Dulaglutide (auto-injector)

Exenatide (timing with meals)

Exenatide ER (both kit and pen require mixing)

Liraglutide (FDA approval for weight loss)


Adverse reaction associated with qweek GLP-1 agonists

injection site reaction more common


Of GLP-1 agonists an DPP4 inhibitors, which have a higher incidence of SEs?

GLP-1 agonists (have improvement in CV markers though!)


Amylin analog MOA

Slows gastric emptying, decreasing glucagon secretion


Advantages of Pramlintide

Decrease postprandial glucose, weight loss


Disadvantages of Pramlintide

A1C reduction 0.5-1%, GI effects, frequent dosing, increases daily injection burden, potential for hypoglycemia with insulin use, spendy


Pramlintide Black Box Warning

Can contribute to episodes of severe hypoglycemia

When initiating, prandial insulin dose needs to be reduced by 50% with subsequent re-titration


Pramlintide adverse effects

Severe hypoglycemia, nausea, decreased appetite, anorexia, vomiting, headache


Pramlintide contraindications

Poor compliance with insulin regimen or with blood glucose monitoring, A1C >9%, recurrent severe hypoglycemia requiring assistance in past 6 months, hypoglycemia unawareness, confirmed gastroparesis, use of drugs that stimulate GI motility, pediatric patients


Pramlintide patient education

Refrigerate unopened pens

Discard opened pens or vials after 30 days

Can NOT be mixed with insulin

Inject SubQ in abdomen or thigh

Separate pramlintide and insulin injections by at least 2 inches

Only take before meals of more than 250 calories (or >30 grams of carbs)

Do not take if pre-meal BG is low or if meal contains insufficient carbs or calories


Special consideration about appearance of NPH



Special consideration about administration of NPH

Can be rolled/mixed (only basal insulin that can be)


Afrezza disadvantages

Boxed warning for acute bronchospasm in patients with chronic lung disease

Contraindicated in asthma and COPD

Not a replacement of long-acting

Not recommended for DKA

Not recommended for patients who smoke or recently stopped


Complicated dosing, expiration and storage


How is Afrezza supplied?

4 units, 8 units or 12 units

Cartridge loaded into small inhaler