Endocrinology: Diabetes: Courses in Therapeutics and Disease State Management

Endocrinology:
Diabetes
Courses in Therapeutics and Disease State Management
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Epidemiology
• Diabetes mellitus (DM) is a metabolic disorder characterized by
hyperglycemia that affects over 29 million Americans.
• Results from defects in insulin secretion, insulin sensitivity, or
both
• Diabetes contributes to microvascular and macrovascular
complications, and is the leading cause of kidney failure in the
U.S.
• In 2012, the burden of diabetes exceeded $245 billion in direct
and indirect costs
American Diabetes Association. “FAST FACTS: Data and Statistics about Diabetes” http://professional.diabetes.org/sites/professional.diabetes.org/files/media/fast_facts_12-2015a.pdf. Updated 12-2015.
Classification
Characteristic Type 1 DM (5% of all cases)* Type 2 DM (90% of all cases)*
Typical age at onset Youth, adolescence Adulthood
Speed of onset Rapid Slow
Response to lifestyle modifications Poor Good
Frequency of DKA High Low
Personal or Family history of autoimmune disease Common Uncommon
Body habitus Lean Overweight, obese, central adiposity
C-Peptide Levels Undetectable to low Normal to high
Evidence of β-cell autoimmunity Present Absent
• Gestational diabetes (GDM) and other forms make up the remaining 5% of cases.
See Table 57-1 in Pharmacotherapy for additional classifications and Table 20.1 in Patient Assessment
Triplitt CL, Repas T, Alvarez C. Chapter 57. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310509. Accessed November 05, 2016.
Herrier RN, Apgar DA, Boyce RW, Foster SL. Diabetes Mellitus. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. New York, NY: McGraw-Hill; 2015.
Screening
• Symptomatic
• Patients presenting with Diabetic Ketoacidosis or Hyperosmolar
Hyperglycemic State
• Generally Type 1 DM or longstanding Type 2 DM
• Asymptomatic
• All adults >45 years old
• Any adult with a BMI ≥ 25kg/m2 (≥23kg/m2 for Asian Americans) with
≥1 diabetes risk factor
• Recheck at a minimum of every 3 years
Diabetes Care 2016;39(Suppl. 1):S1–S108
Diabetes Risk Factors
• Physical inactivity
• First degree relative with diabetes
• African American, Latino, Native American, Asian American, Pacific
Islander
• Women with PCOS, a history of GDM or delivering a baby weighing
>9lbs
• Hypertension, HDL <35mg/dL, or triglycerides >250mg/dL
• A1c ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose
• Conditions associated with insulin resistance
• Cardiovascular disease Diabetes Care 2016;39(Suppl. 1):S1–S108
Diabetes Risk Factors
• Physical inactivity
• First degree relative with diabetes
• African American, Latino, Native American, Asian American, Pacific
Islander
• Women with PCOS, a history of GDM or delivering a baby weighing
>9lbs
• Hypertension, HDL <35mg/dL, or triglycerides >250mg/dL
• A1c ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose
• Conditions associated with insulin resistance
• Link: Figure of acanthosis nigricans, with typical hyperpigmented
plaques on a velvet-like, verrucous surface on the neck.
• Cardiovascular disease Diabetes Care 2016;39(Suppl. 1):S1–S108
Diagnosis
Pre-Diabetes Diabetes
• HbA1c 5.7%-6.4% • HbA1c ≥6.5%
• Fasting plasma glucose 100- • Fasting plasma glucose ≥126
mg/dL (Fasting is defined as no
125mg/dL caloric intake for at least 8
• IFG=Impaired Fasting Glucose hours)
• 2-hour plasma glucose 140- • 2-hour plasma glucose ≥200
199mg/dL during an OGTT mg/dL during an OGTT
• IGT=Impaired Glucose • In a patient with classic
Tolerance symptoms of hyperglycemia or
hyperglycemic crisis, a random
plasma glucose concentration
≥200 mg/dL
Concept Review
• GC is 24 year-old, obese, white female seen in family medicine
clinic to establish care. She has a history of polycystic ovarian
syndrome. Her family history is unknown. She denies tobacco
and alcohol use. Endorses polydipsia with polyuria and
oligomenorrhea with moderate to heavy menstrual bleeding.
• Height: 5 ft 7in Weight: 300lbs BMI: 47 kg/m2
• BP: 140/101
• Is GC a candidate for diabetes screening?
Concept Review
• GC is ordered screening labs based on her BMI and diabetes
risk factors.
• Her results:
• HbA1c 10.6%
• Plasma Glucose (non-fasting) 325mg/dL
• What diagnosis, if any, can be made today?
• Link: Table of a list of other assessments that should be
completed at the initial visit.
• How should we approach treatment?
Goals of Treatment
• Prevent Acute Complications
• Prevent Chronic Complications
• Alleviate Symptoms of Complications
• Minimize/Avoid Drug Related Problems
Glycemic Control
• Self-Monitoring of Blood Glucose (SMBG)
• Part of the patient’s self-management strategy
• Pre-prandial is the primary target
• Symptoms of hypo-/hyperglycemia
• Individualized for the needs and goals of the patient
• HbA1c
• Glycosylated hemoglobin on RBCs
• Every 3 months
• “average blood glucose”
• Target to prevent complications
SMBG
• Measured using blood glucose meter
• Link: Video on Home Blood Glucose Monitoring
• Link: Video on Preventing Infections When Monitoring Blood
Glucose
• ADA recommendations
• Preprandial
• Goal 80-130mg/dL
• Postprandial
• Goal <180mg/dL
• Hypoglycemia
• Any value <70mg/dL Diabetes Care 2016;39(Suppl. 1):S1–S108
SMBG
Patients using multiple
insulin injections per day Non-intensive regimens
• Before meals and snacks • Oral agents only
• Occasionally postprandially • Monitoring for hypoglycemia
• May help guide treatment
• At bedtime decisions
• Prior to exercise or • Basal Insulin
performing critical tasks • Fasting SMBG for titration of
• When suspect the presence basal insulin dose
of, and after treating • Monitoring for hypoglycemia
hypoglycemia Diabetes Care 2016;39(Suppl. 1):S1–S108
HbA1c
• A1C is influenced by both the fasting glucose and post-prandial levels
• Estimated Average Glucose eAG= 28.7 X A1C – 46.7
• Link: eAG/A1C Conversion Calculator
• Link: Infographic on A1C Goals
• Measured every 3-6 months
• Goal for most patients is <7%
• More stringent goals (<6.5%) can be considered if:
• Hypoglycemia can be avoided
• Short duration of diabetes
• Long life expectancy
• No significant CVD
• Less stringent goals (<8%) can be considered if:
• Severe hypoglycemia
• Limited life expectancy
• Advanced complications/Longstanding disease
• Extensive comorbidities
Concept Review
• GC is 24 year-old, obese, white female
• History of polycystic ovarian syndrome.
• Family history is unknown.
• Denies tobacco and alcohol use.
• Endorses polydipsia with polyuria and oligomenorrhea with moderate to heavy
menstrual bleeding.
• Vitals/Labs
• BP: 140/101
• HbA1c 10.6%
• What glycemic targets would you recommend for GC?
• Link: Table on Treatment Goals for Adults with Diabetes
Comprehensive Assessment
• Link: Table of Guidelines on for Ongoing, Comprehensive
Medical Care for Patients with Diabetes
• Medical History
• Physical Exam
• Laboratory Evaluation
• Referrals
Acute Complications
Symptoms of Hyperglycemia
• Include: • Drugs that cause hyperglycemia
• Polyuria • Corticosteroids
• Polydipsia • Niacin
• Polyphagia • Atypical Antipsychotics
• Protease inhibitors
• Dry Skin
• Sympathomimetics
• Nausea
• Fatigue/Drowsiness • Treatment
• Blurred vision • Additional insulin
• Moderation of carbohydrate intake
• May be caused by: • Physical activity
• Too much food
• Too little insulin/medication
• Illness, stress
• Link: Table on Medications that may
Affect Glycemic Control
Acute Complications
Impaired Wound Healing and Infection
• Impaired wound healing • Vaginal candidiasis
• Urinary tract
• Skin infections
• Foot Infections • Causes
• Treatment • Increased susceptibility
• Prevention through foot care • Decreased healing
• Glycemic control • Treatment
• Referral to podiatry • Prevention
• Link: Video on Diabetic Foot Exam
• Link: Algorithm covering pathophysiology of • Immunizations
the diabetic foot • Influenza-yearly
• Infection •
•
Pneumococcal
Tetanus
• Skin • Hepatitis B vaccine
• Oral
• Genitourinary
Hyperglycemic Crises
Hyperosmolar
Diabetic ketoacidosis
hyperglycemic state
(DKA)
• Causes • Causes
(HHS)
• Decreased insulin • Inadequate insulin levels to utilize
• Increased counter-regulatory glucose
hormone
• Release of free fatty acids (lipolysis) • Enough insulin to prevent lipolysis
that are oxidized to ketone bodies • Glycosuria leads to osmotic
• Results in metabolic acidosis diuresis
• Presentation • Presentation
• Acute presentation (<24 hours)
• Evolves over several days to
• Can occur with BG >250
weeks
• Usually Type 1 DM, can be
precipitated in Type 2 by • Occurs with BG >600
infection/stress
Author: Autumn Stewart, PharmD, BCACP, or drugs
CTTS; • University
Associate Professor of Pharmacy Practice; Duquesne TypeSchool2 ofDM
Pharmacy
Hyperglycemic Crises
• Symptoms
• Hyperglycemia
• Vomiting
• Weight loss
• Dehydration
• Weakness
• Clouding of sensorial
• Coma
• Tachycardia
• Hypotension
• Abdominal pain (DKA only)
Chronic Complications
Microvascular
• Retinopathy
• Leading cause of new blindness
• Edema
• Non-proliferative diabetic retinopathy-microaneurysms, hemorrhages
• Proliferative diabetic retinopathy-growth of new blood vessels into optic nerve and
macula; hemorrhage, retinal detachment
• Prevention
• Glycemic control
• Blood pressure control
• Fundoscopic Eye Exam
• Type 1- initial exam or within 5 years after disease onset, annually thereafter
• Type 2- initial exam shortly after the diagnosis of diabetes, annually thereafter
• Laser treatment to prevent vision loss, intravitreal anti-VEGF agents
• Link: Figure of a patient has neovascular vessels proliferating from
the optic disc
Microvascular
• Nephropathy
• Leading cause of ESRD
• Link: Algorithm for screening for microalbuminuria
• Annual urine microalbumin/creatinine ratio
• Annual serum creatinine (even patients without kidney damage)
• Prevention
• Glycemic control
• Blood pressure control
• Compelling indication for use of ACEI or ARB
• Treatment
• ACEI prevents CVD events AND slows the decline in renal function
• ARB prevents progression of albuminuria
• Link: Figure on time course of development of diabetic nephropathy
• Can use either ACEI or ARB in normotensive patients with elevated urinary albumin
Microvascular
• Neuropathy vibration perception
• Autonomic • Orthostatic BP measurements
• Erectile Dysfunction • A fall in systolic blood pressure >20
• Link: Chapter on ED on AccessPharmacy mmHg upon standing without an
• Cardiac appropriate heart rate response
• Resting tachycardia • Heart rate measurements (>100bpm)
• Orthostasis • Treatment
• Gastroparesis
• Link: Chapter on Nausea and Vomiting on • Erectile dysfunction
AccessPharmacy • Link: Algorithm for selecting treatment for erectile
• Sensory dysfunction
• Diabetic Peripheral Neuropathy • phosphodiesterase type 5 inhibitors
• Numbness, tingling, burning, loss of • intracorporeal or intraurethral
sensation esp. in extremities prostaglandins
• Screening • vacuum devices
• Foot exam at each visit • Gastroparesis
• Link: Video on Diabetic Foot Exam • Erythromycin
• Pulses (dorsal pedal and post tibial) • Metoclopramide
• Monofilament testing (loss of protective • Diabetic Peripheral Neuropathy (DPN)
sensation) • Link: Table on Pharmacologic Management of Chronic
• Vibration using 128-Hz tuning fork, OR, Noncancer Pain
pinprick sensation, OR ankle reflexes, OR
Macrovascular
• Blood Pressure
• Checked at each visit
• Link: Table on Blood Pressure Technique
ADA 2016 Standards JNC8

Systolic Goal <140mmHg (<130mmHg may be appropriate in younger patients; those with
albuminuria; additional ASCVD risk factors. If achieved without undue <140mmHg
treatment burden.)
Diastolic Goal <90mmHg (< 80mmHg may be appropriate in younger patients; those with
albuminuria; additional ASCVD risk factors. If achieved without undue < 90mmHg
treatment burden.)
Drug Therapy CKD: ACEI or ARB
ACEI or ARB for all patients with diabetes
Nonblack persons: ACEI, ARB, Thiazide, or
Administer 1 or more antihypertensive meds at HS
CCB
Add on amlodipine, HCTZ or chlorthalidone
Black persons: Thiazide or CCB
James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013.
doi:10.1001/jama.2013.284427.
Macrovascular
• Lipids
• Lipid panel at least annually
• Link: Figure on Four Major Statin Benefit Groups
• Moderate intensity statin if age 40-75 with diabetes (Level of evidence: A)
• High intensity statin if age 40-75 with diabetes and a ≥7.5% 10 year ASCVD risk. (Level of
evidence: E)
• Evaluate benefit vs risk in patients <40 and >75 with diabetes (Level of evidence: E)
• 10-Year Risk can be calculated using the ASCVD Pooled Cohort Equations CV Risk Calculator
• Link: Algorithm covering major recommendations for statin therapy for atherosclerotic
cardiovascular disease (ASCVD) prevention
• Link: Figure on intensity levels of statins
Stone NJ, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. Circulation. 2013;00:000–000
Macrovascular
• Antiplatelet therapy
• Aspirin 75-162 mg/day
• Primary Prevention
• MEN and WOMEN > 50 with at least 1 additional major risk factor
• family history of CVD, hypertension, smoking, dyslipidemia, albuminuria
• Secondary prevention
• Recommended for ALL patients with previous MI or stroke
• Smoking Cessation
• Pharmacotherapy and Support programs—“The 5 A’s”
Medical Nutrition Therapy
Carbohydrates in diabetes management
• The carbohydrate amount in meals and available insulin are usually the most important
factors influencing glycemic response after eating and should be considered when
developing the eating plan.
• Includes carbohydrate from fruits, vegetables, whole grains, legumes, and low-fat milk
(sucrose-containing foods in place of other carbohydrates should not displace nutrient
dense food choices.
• Monitoring carbohydrate, whether by carbohydrate counting, exchanges, or experienced-
based estimation, remains a key strategy in achieving glycemic control.
• For example: 200 grams of carbohydrates per day 45-60 grams per meal; 15-20 grams
for snacks
• Avoid excess calories (adjust to maintain desirable weight or prevent weight gain)
• Consume a variety of fiber containing foods (20-30 grams of dietary fiber per day)
• People with diabetes or pre-diabetes should limit/avoid intake of sugar-sweetened
beverages to reduce risk for weight gain and worsening of cardio-metabolic risk.
• Sugar alcohols and nonnutritive sweeteners are safe within recommended daily intake
levels
Fat and cholesterol in diabetes management
• Limit saturated fat to <7% of total calories
• Minimize intake of trans fat and reduce dietary cholesterol to <200
mg/day
• Two or more servings of fish per week provide n-3 polyunsaturated
fatty acids
Protein in diabetes management
• If normal renal function, no need to restrict usual protein intake
• Protein should not be used to treat acute or prevent nighttime
hypoglycemia
Alcohol in diabetes management
• Limit daily intake to one drink per day or less for women and two drinks
per day or less for men
• Alcohol may increase risk for hypoglycemia, especially if taking insulin
or insulin secretagogues
Sodium
• Reduce sodium to < 2,300 mg/day; for individuals with both diabetes
and hypertension, further reduction in sodium intake should be
individualized
Insulin Basal (Background Insulin)
Intermediate Long acting Ultra Long Acting
Glargine U-
Glargine U- Degludec (Tresiba®)
NPH (Humulin N®, and 100 Detemir
300 100units/ml and
Novolin N®) (Lantus®, (Levemir®)
(Toujeo®) 200units/ml
Basaglar®)
Can be dosed
Can be dosed QD at dinner QD at dinner
Dosed once daily at any
or HS; or Daily at same time or HS; or
time of day (must
BID (at breakfast and BID (at
separate by >8 hours)
dinner or HS) breakfast and
dinner or HS)
Cloudy Clear
Can be mixed with R or
Rapid acting insulin by Cannot be mixed with other insulin
patient or premixed
Link: Table on Available Injectable and Insulin Preparations
Link: Table on Pharmacokinetics of Various Insulins

Administered Subcutaneously
Insulin Bolus (Mealtime Insulin)
Short acting Rapid acting
Glulisine
Regular (Humulin R®, Novolin R®) Lispro (Humalog®) Aspart (Novolog®)
(Apidra®)
Clear Clear
NovoLog Mix 70/30®
Humalog Mix 50/50® (70% NPH; 30%
Aspart); Ryzodeg® Can be
Humulin 70/30®; Novolin 70/30® (50% NPH; 50% Lispro);
(70% degludec/30% mixed with
(70% NPH; 30% Regular) Humalog Mix 75/25®
Aspart), NPH
(75% NPH; 25% Lispro)
Link: Graphic on insulin action
Link: Table on Available Injectable and Insulin Preparations
Link: Table on Pharmacokinetics of Various Insulins

Administered Subcutaneously
Injecting Insulin
• Link: Video on Drawing and • Subcutaneous Injection sites
Preparation of Diabetic • Abdomen (most predictable)
Injections • Outer upper arm
• Buttocks
• Hip
• Front and side of the thigh
(most likely affected by
exercise
Pharmacotherapy in Type 1 Diabetes
• Intermediate or Long-acting Basal Insulin AND Pre-meal Rapid
or Short Acting Insulin
• Continuous Subcutaneous Insulin Infusion (CSII) aka “Insulin
Pump”
• Link: Figure on relationship between insulin and glucose over
the course of a day and how various insulin and amylinomimetic
regimens could be given.
• Link: Chapter on Pancreatic Hormones & Antidiabetic Drugs
Insulin Regimen Profiles
Commonly used insulin regimens.
Panel A shows administration of a long-acting insulin like

glargine (detemir could also be used but often requires
twice-daily administration) to provide basal insulin and a
pre-meal short-acting insulin analog.
Panel B shows a less intensive insulin regimen with BID

injection of NPH insulin providing basal insulin and regular
insulin or an insulin analog providing meal-time insulin
coverage. Only 1 type of shorting-acting insulin would be
used.
Panel C shows the insulin level attained following

subcutaneous insulin (short-acting insulin analog) by an
insulin pump programmed to deliver different basal rates. At
each meal, an insulin bolus is delivered. B, breakfast; L,
lunch; S, supper; HS, bedtime. Upward arrow shows insulin
administration at mealtime.
Initiating Insulin in Type 1 Diabetes
• Use an empiric dose (best “estimate” based on actual weight)
• Initial 0.5-0.7 U/kg/day [Total Daily Dose (TDD)]
• May drop to 0.2-0.5 U/kg/day during “honeymoon phase” as glucose toxicity
resolves
• May increase to 1-1.5 U/kg/day during illness or growth
• Since patients with Type 1 diabetes need a regimen of BASAL and
BOLUS insulin, the TDD needs to be split. Usually start with a
Basal-to-Bolus ratio of 50:50.
• Newly diagnosed Type 1 diabetic weighing 114 lbs. What is a
reasonable initial total daily dose (TDD) of insulin?
• Using the TDD calculated above, what doses of basal and bolus
insulin would the patient be started on?
Initiating Insulin in Type 1 Diabetes
• 114 lbs ÷ 2.2 lbs/kg = 52 kg
• TDD = 0.5-0.7 U/kg/day = 26-36 units
• Using 26 units as the TDD
• 50% Basal = ~14 units QD
• 50% Bolus = 3 units breakfast, lunch, 4 units dinner
Adjusting Insulin Doses
• Fixed Dose Approach
• Look for patterns/trends in SMBG and patient characteristics to adjust and provide patient
with a fixed prandial insulin dose.
• Dose adjustments by 1-2 units every few days
• Patient must be consistent in carbohydrate amounts at each meal
• Flexible Meal Dosing Approach
• Patients can have more flexibility from meal to meal by injecting per sliding scale to
correct an elevation (correction dose) and provide coverage for carbohydrates in the
meal.
• Amount of insulin to inject depends on insulin sensitivity and amount of carbs in the meal
• Correction dose calculated from patient’s insulin sensitivity (ranges from 1 U per 25mg/dL
to 1 U per >60mg/dL). A conservative correction factor is 1 U per 50mg/dL.
• (measured blood glucose mg/dL – goal blood glucose mg/dL) ÷ Correction factor mg/dL/U =
Correction dose
• Patients will also estimate pre-meal insulin requirements based on anticipated
carbohydrates in meal (ranges 1 U for every 6 g of CHO up to 20 g of CHO).
• 1 U per 15 g CHO is good starting place
• Carbohydrates in meal g ÷ insulin:carb ratio = Units of insulin
• Lifestyle modifications
• Oral agents
• Non-insulin injectables
• Insulin
Link: Infographic from the ADA 2017 Guidelines covering general

recommendations for Antihyperglycemic therapy in Type 2
Diabetes.
Metformin
• Biguanide
• Primarily decreases hepatic glucose production; also increases
peripheral insulin sensitivity
• Initial dose 500mg QD-BID with food. Titrated to maximum
effective daily dose of 2000mg.
• Contraindicated at eGFR<30ml/min; not recommended to start
when eGFR 30-45ml/min.
• Hold for 48 hours following iodinated contrast imaging if
eGFR<60ml/min, or if liver disease, alcoholism, or heart failure
U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function
http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm. Accessed November 12, 2016.
Metformin
• Monitoring
• Diarrhea and abdominal cramping
• Lactic acidosis (rare)
• CBC/B12 levels Initial dose 500mg QD-BID with food. Titrated to
maximum effective daily dose of 2000mg.
• Advantages
• Low risk for hypoglycemia as monotherapy
• Weight loss/weight neutral
• Long term safety record
• Low cost
• Efficacious
Concept Review
• GC is 24 year-old, obese, white female with a new diagnosis of
Type 2 Diabetes and a history of polycystic ovarian syndrome.
Her family history is unknown. She denies tobacco and alcohol
use.
• BP: 140/101
• HbA1c 10.6%
• Creatinine 0.8mg/dL
• How should we approach treatment?
Selecting Add-on Therapy
• Efficacy Link: Table on Oral Agents for the Treatment of
• Mechanism of action Type 2 Diabetes Mellitus
• Cost
• Safety
• Contraindications
• Adverse effect profile
• Risk for hypoglycemia
• Extraglycemic effects
• Lipids
• Weight
• Blood pressure
Patient Centered Considerations
Avoiding Hypoglycemia Avoiding Weight Gain Lower Costs
Metformin Metformin Metformin
Thiazolidinediones SGLT-2 Inhibitors Sulfonylureas
SGLT-2 Inhibitors GLP-1 Agonists Thiazolidinediones
GLP-1 Agonists DPP-IV Inhibitors Basal Insulin (NPH)
DPP-IV Inhibitors
Sulfonylureas
• Enhance insulin secretion
• Glimepiride (Amaryl®)
• Initial: 1-2mg QD with breakfast; then 1-4mg QD. Max: 8mg QD
• Glipizide (Glucotrol®, Glucotrol XL®)
• Initial: 5mg QD 30 minutes before breakfast and titrate by 2.5-5mg Max:
20mg BID
• XL Initial: 5mg QD with breakfast. Max: 20mg QD
• Glyburide (Diabeta®, Micronase®) +metformin (Glucovance®)
• Initial: 2.5mg QD with breakfast and titrate by 2.5mg q week. Max: 20mg
QD;
• Do not use in eGFR below 60ml/min
Sulfonylureas
• Interact with CYP2C9 inducers and inhibitors
• Monitoring
• Hypoglycemia
• Weight gain
• Advantages
• Long term safety record
• Low cost
• Efficacious
Meglitinides
• Stimulate insulin secretion
• Repaglinide (Prandin®)
• Initial: 0.5mg TID within 15-30 minutes before the start of each meal.
Titrate by doubling dose every week Max: 16mg a day
• Nateglinide (Starlix®)
• 120mg TID within 30 minutes before the start of each meal
Meglitinides
• Interact with CYP2C8 and CYP3A4 inducers and inhibitors
• Monitoring
• Hypoglycemia
• Weight gain
• Advantages
• More flexible dosing and less hypoglycemia compared to sulfonylureas
Thiazolidinediones
• Increase peripheral insulin sensitivity; decrease hepatic glucose
• Pioglitazone (Actos®) +metformin (ActosPlusMet®)
• Initial: 15-30mg QD; titrate to 45mg QD in 3-4 weeks Max: 45mg QD
• Interact with CYP2C8 and CYP3A4 inducers and inhibitors
• Monitoring
• Weight gain/edema
• AST/ALT
• Heart Failure
• Fractures
• Advantages
• No hypoglycemia
DPP-IV Inhibitors
• Reduce glucagon and improve insulin response to hyperglycemia
• Sitagliptin (Januvia®) +metformin (JanuMET®)
• Initial/typical: 100mg QD; Renal dosing: CrCl 30-50ml/min: 50mg QD; CrCl
<30ml/min:25mg
• Saxagliptin (Onglyza®) +metformin (Kombiglyze®)
• Initial/typical: 2.5-5 mg once daily; Renal dosing: CrCl <50ml/min: 2.5mg;
CYP3A4/5 (-): 2.5mg
• Linagliptin (Tradjenta®) +metformin (Jentadueto®)
• Initial/typical: 5 mg QD
• Alogliptin (Nesina®) +metformin (Kazano®)
• Initial/typical: 25 mg QD Renal dose: CrCl 30-60 ml/min: 12.5mg; <30
ml/min: 6.25mg
DPP-IV Inhibitors
• Monitoring
• Urticaria
• Angioedema
• Pancreatitis
• Worsening of heart failure
• Advantages
• Low risk for hypoglycemia
• Weight neutral
SGLT2 Inhibitors
• Increase urinary excretion of glucose
• Canagliflozin (Invokana®); +metformin (Invokamet®)
• Initial/typical: 100mg QAM, titrate 300mg QD
• Renal dose 100mg eGFR<60. Do not use below 45ml/min
• Dapagliflozin (Farxiga®); +metformin (Xigduo XR®)
• Initial/typical: 5mg QAM, titrate 10mg QD
• Empagliflozin (Jardiance®); +metformin (Synjardy®); +linagliptin (Glyxambi®)
• Initial/typical: 10mg QAM, titrated to 25mg QAM
SGLT2 Inhibitors
• Monitoring
• Genital mycotic infections
• Urinary tract infections
• Orthostatic hypotension
• DKA
• Advantages
• No hypoglycemia
• Weight loss
• Convenient, daily dosing, in the morning
GLP-1 Agonists
• Enhance insulin secretion (glucose-dependent), reduce postprandial
glucagon secretion and increase satiety and slow gastric emptying
• Exenatide (Byetta®)
• Initial: 5mcg BID, 10mcg BID after 1 month. Give 60min before meals
• Exenatide ER (Bydureon®)
• Initial: 2mg SQ weekly
• Liraglutide (Victoza®)
• Initial: 0.6 mg QD AC for 1 week; then 1.2 mg QD; Max: 1.8 mg QD
• Dulaglutide (Trulicity®)
• Initial: 0.75mg SQ weekly, can increase to 1.5mg
• Albiglutide (Tanzeum®)
• Initial: 30mg SQ weekly, can increase to 50mg
GLP-1 Agonists
• Monitoring
• GI upset (contraindicated in gastroparesis)
• Injection site reactions
• Gall bladder disease
• Pancreatitis
• Advantages
• No hypoglycemia
• Weight loss
• Efficacious
Basal insulin
• Most effective add-on therapy
• Titrated to bring AM fasting SMBG in range
• Mealtime bolus insulin added if A1c not at goal and/or as TDD
approaches 0.5 units/kg/day
• Link: Insulin algorithm for type 2 diabetes mellitus in children
and adults; initiation of once-daily therapy
• Hypoglycemia and injection site reactions
Concept Review
• GC returns for a follow-up 3 months later and is tolerating metformin
at 1000mg BID. Blood glucose readings after dinner 180-240’s. Has
not met with dietician yet, but plans to in near future. Prior to
appointment, patient has labs drawn: HbA1c 8.3% Glucose (non
fasting) 192mg/dL
• What options are available as add-on therapy for GC’s diabetes
management?
• How would the options change if she:
• Was 74 with an eGFR < 50ml/min?
• Was an uncircumcised male with a history of balanitis?
• Had a history of irritable bowel syndrome?
• Was 65 with an ejection fraction of 35% on diuretics?
• Had difficulty affording her medications?
Treatment Pre-Diabetes
• Patients with IGT, IFG, or an A1c 5.7-6.4%
• Intensive lifestyle modification is most effective (~58% reduction in 3 years)
• 7% weight loss
• 150 min/week of moderate intensity physical activity
• Drug therapy (not as effective as lifestyle)
• Metformin
• Those with BMI >35kg/m2
• Aged less than 60 years old
• Women with history of GDM
• Assessment and management of cardiovascular risk factors
• Obesity
• Hypertension
• Hyperlipidemia
• Smoking cessation
Preventing and Avoiding Drug Related
Problems
• Hypoglycemia
• Regular assessment
• Identify causes
• Education
• Appropriate treatment
• Medication Safety
• Heart failure
• Impaired renal function
• Gastrointestinal disease
• Pancreatitis
• Genitourinary symptoms
• Patient education on side effects
• Anticipated side effects
• How to manage/prevent
• When to report

Endocrinology: Diabetes: Courses in Therapeutics and Disease State Management

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Endocrinology: Diabetes: Courses in Therapeutics and Disease State Management

Uploaded by

Copyright:

Available Formats

Endocrinology:

Speed of onset Rapid Slow

Response to lifestyle modifications Poor Good

Frequency of DKA High Low

Personal or Family history of autoimmune disease Common Uncommon

Body habitus Lean Overweight, obese, central adiposity

C-Peptide Levels Undetectable to low Normal to high

Evidence of β-cell autoimmunity Present Absent

Diabetes Care 2016;39(Suppl. 1):S1–S108

ADA 2016 Standards JNC8

Link: Table on Available Injectable and Insulin Preparations

Link: Table on Pharmacokinetics of Various Insulins

Link: Graphic on insulin action

Link: Table on Available Injectable and Insulin Preparations

Link: Table on Pharmacokinetics of Various Insulins

Panel A shows administration of a long-acting insulin like

Panel B shows a less intensive insulin regimen with BID

Panel C shows the insulin level attained following

Link: Infographic from the ADA 2017 Guidelines covering general

You might also like