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MENNONITE COLLEGE OF NURSING
AT
ILLINOIS STATE UNIVERSITY
Pharmacotherapeutics for Advanced Practice Nursing 433
Drugs Affecting Endocrine and Metabolic Function
Thyroid Hormones
A little A & P review…
 Hypothalamus  TRH (thyrotropin releasing hormone) Pituitary  TSH (thyroidstimulating hormone) Thyroid  T4, which is converted to T3 in the tissues of the
thyroid, liver, and brain
 The thyroid cells put iodine and tyrosine together to form T4.
 Thyroxine (T4) and triiodothyronine (T3) are the two hormones produced by the
thyroid gland. T4 has 4 iodine atoms; conversion causes loss of 1 iodine atom and
the resultant T3. 80% of thyroid hormone is T4; 20% is T3. T3 is 40X more potent
than T4.
Hypothyroidism
 Types of hypothyroidism
o Primary hypothyroidism is caused by an abnormality in the thyroid gland
itself.
o Secondary hypothyroidism may result from a dysfunctional pituitary gland
(lowered TSH level).
o Tertiary hypothyroidism is due to hypothalamic rather than pituitary
dysfunction (lowered TRH level)
 Tertiary hypothyroidism similar to secondary in that the stimulus
needed for secretion of thyroid hormone is absent.
o All three types of hypothyroidism are amenable to thyroid hormone
replacement.

Thyroid replacement
o Given to replace what the thyroid gland cannot itself produce in order to
achieve normal thyroid levels (euthyroid)
o Natural and synthetic thyroid hormone
 Natural preparations are derived from animal thyroid and include
thyroid and thyroglobulin
 Synthetic preparations include:
 levothyroxine (Levoxine, Synthroid, Levoxyl) = synthetic T4
 liothyronine (Cytomel) = synthetic T3
 liotrix (Thyrolar, Euthroid) = synthetic T3/T4 combination
 Levothyroxine is the preferred agent because its hormonal content is
standardized and its effect is therefore predictable.
o Dosing: Start low and go slow!
 With levothyroxine (Synthroid, for example), starting dosages:
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o
o
o
o
o
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If young, OK  start on 0.1 mg po/day
If > 45 yr. old, no CV disease  start on 0.05 mg/day
If elderly, have CV disease, have longstanding hypothyroidism
 started on 0.025 mg/day
 Increase dosage by 0.025 mg every 4 weeks until TSH within normal
limits
 Elderly patients are much more sensitive to thyroid hormone
replacement therapy  more liable to suffer more adverse reactions to
thyroid hormones than patients in any other age group.
 Because the symptoms of hypothyroidism may be confused
with those of other diseases, nonspecific symptoms such as
stumbling, falling, depression, incontinence, cold intolerance,
and weight gain should be thoroughly evaluated and
documented before a diagnosis of hypothyroidism is rendered.
Contraindicated in adrenal insufficiency, MI, hyperthyroidism
Common adverse effects
 Usually result of overdose (s/sx of hyperthyroidism)
 CNS: insomnia, tremors, headache
 CV: tachycardia, palpitations, angina, dysrhythmias, HTN, cardiac
arrest
 GI: N, diarrhea, increased or decreased appetite, cramps
 Other: menstrual irregularities, weight loss, sweating, heat
intolerance, fever, thyroid storm
Interactions
 For patients on Coumadin (warfarin), the addition of thyroid hormones
leads to increased catabolism of clotting factors, resulting in an
increased INR. A decrease in Coumadin may be needed, but should be
based on careful monitoring of the Protime/INR.
  oral absorption of cholestyramine (antilipemic agent)
 Diabetics – may need to  dose of hypoglycemic agents
 Thyroid + epinephrine in patients with coronary disease may 
cardiac insufficiency
Patients on thyroid hormone replacement therapy should avoid adding iodine
food containing iodized salt, soybeans, tofu, turnips, some types of seafood,
and some breads.
Important to take the medication exactly as prescribed, at the same time
everyday, and not to switch brands, unless approved by the health care
provider
Therapeutic effects of thyroid agents may take several months to occur
Hyperthyroidism
 Caused by excessive secretion of thyroid hormone from the thyroid gland
 Due to different diseases or drugs
 Diseases = Graves’ disease (includes hyperthyroidism with diffuse goiter or thyroid
gland enlargement), and multinodular disease
 Treated with surgery or antithyroid drugs

Antithyroid drugs
o Called thioamide derivatives and consist of mainly methimazole (Tapazole)
and propylthiouracil (PTU)
o Drugs act by inhibiting the incorporation of iodine molecules into the amino
acid tyrosine, a process required to make the precursors of T3 and T4
 PTU also inhibits conversion of T4 to T3 in the peripheral circulation
o By inhibiting the formation of the precursors of thyroid hormone, they prevent
its formation.
o Neither drug can inactivate already existing thyroid hormone
o Common adverse effects of antithyroid medications (watch for bone marrow
and liver toxicity)
 CNS: drowsiness, headache, vertigo, fever, paresthesia
 Skin: rash, pruritus, hyperpigmentation
 GI: N & V, diarrhea, jaundice, hepatitis, loss of taste
 MSK: myalgia, arthralgia, nocturnal muscle cramps
 Hematologic: agranulocytosis, leukopenia, thrombocytopenia,
hypothrombinemia, lymphadenopathy, bleeding
 Other: enlarged thyroid, nephritis
o Interactions
 Additive agranulocytosis with other bone marrow depressants
 Increased activity of oral anticoagulants
Adrenal Hormones
Adrenal gland characteristics
Adrenal cortex
 Endocrine tissue
 2 types of hormones
 glucocorticoids (betamethasone, corticotropin [ACTH], cortisone,
dexamethasone, hydrocortisone, methylprednisolone, paramethasone,
prednisolone, triamcinolone)
 Biologic functions
 Anti-inflammatory actions
 Maintenance of normal blood pressure
 Carbohydrate and protein metabolism
 Fat metabolism
 Stress effects
 mineralcorticoids (aldosterone, fludrocortisone, desoxycorticosterone)
 Biologic functions
 Sodium and water resorption
 Blood pressure control
 Potassium levels and pH of blood
Adrenal medulla
 Neuroendocrine tissue
 1 type of hormone
 catecholamines (epinephrine, norepinephrine)
 Diseases
 Addison’s disease = failure of adrenocortical function (undersecretion)
 Cushing’s disease = oversecretion
Synthetic corticosteroids available in several forms
 Topical (for dermatitis)
 Nasal spray (for allergic rhinitis)
 Inhalers (for asthma)
 Intra-articular
 Systemic (oral, IM, IV)
 Can be given short term (as with Medrol Dose Pak)
 Can be given on a regular basis
Examples of corticosteroids
 Hydrocortisone (Cortef, Hydrocortone, Solu-Cortef) = natural short-acting
glucocorticoid
 Prednisone (Deltasone) = synthetic intermediate-acting glucocorticoid
 Dexamethasone (Decadron) = synthetic long-acting glucocorticoid
Adrenocortical hormones used to treat:
 Adrenocortical deficiency
 Bacterial meningitis
 Cerebral edema
 SLE
 Dermatologic disease
 Endocrine disorders
 GI diseases (ulcerative colitis)
 Hematologic
 Ophthalmology
 Transplants
 SCI
 Polymyalgia rheumatia (PMR)
 Temporal arteritis (giant cell arteritis)
 Rheumatoid arthritis
 Tendonitis
 Low back pain
 Bell’s palsy
Corticosteroids: Common Adverse Effects
 CNS: convulsions, HA, vertigo, mood swings, psychic impairment, insomnia
 CV: CHF, cardiac edema, HTN (all due to electrolyte imbalances)
 High-dose corticosteroid therapy (≥ 7.5 mg/day) increases the risk of
developing atrial fibrillation
 Endocrine: growth suppression, Cushing’s syndrome, menstrual irregularities,
carbohydrate intolerance, hyperglycemia, HPA axis suppression
 Cushingoid symptoms include moon face, weight gain, muscle wasting, and
increased deposition of fat in the trunk area, leading to truncal obesity
 GI: peptic ulcers with possible perforation, pancreatitis, ulcerative esophagitis,
abdominal distention
 Skin: fragile skin, petechiae, ecchymoses, facial erythema, poor wound healing,
hirsutism, urticaria
 MSK: osteoporosis, muscle weakness, loss of muscle mass, avascular necrosis
 Ocular: increased IOP, glaucoma, exophthalmos, cataracts
 Immunity: Increased risk of infection
Interactions
 With non-potassium sparing diuretics (thiazides, loop)  severe hypocalcemia
 With ASA, NSAIDs, ulcerogenic drugs  additive effects
 With anticholinesterase drugs  weakness in myasthenia gravis patients
 Patient teaching: once-a-day dosing corticosteroids should be administered
between 6 and 8 a.m. to minimize adrenal suppression.
Sudden discontinuation of adrenal agents can precipitate an adrenal crisis caused
by a sudden drop in the serum levels of cortisone.
 The higher the dosage and the longer the duration of therapy, the more difficult
the process of tapering.
 The administration of glucocorticoids for a short time (< 14 days) is relatively
safe.
 Suppression of the HPA axis can occur with use of “superpotent” topical
steroids such as betamethasone dipropionate (Diprosone) and clobetasol
propionate (Temovate) ointments.
 Application of high-potency corticosteroids should be limited, when
possible, to twice-daily dosing and to no more than 3-4 weeks.
 Adrenal suppression has even been reported to occur after prolonged use of a
steroid nasal spray (1992 study)
Algorithm for corticosteroid withdrawal
Source: Kountz, DS & Clark, CL (February 1, 1997). Safely withdrawing patients from
chronic glucocorticoid therapy. American Family Physician, 55(2), 521-525.

Need to adjust steroid dosage and plan rate of withdrawal to prevent relapse of the
disease and allow the HPA axis to recover its physiologic function.


Before starting the steroid withdrawal program, the health care provider should
review the signs and symptoms that suggest adrenal insufficiency with the patient
and family
 Medic-Alert bracelet indicating steroid dependency
 Prepackaged syringe of dexamethasone (Decadron) 4 mg, for family members
of the patient to administer in case of unexplained loss of consciousness.
Stage 1: Gradually decrease dosage until a dosage of 5 mg per day of prednisone
or equivalent is reached
 As the corticosteroid is tapered, the patient may experience some mild
withdrawal symptoms, including fatigue, anorexia, nausea and orthostatic
dizziness
 During this taping period the patient is most vulnerable to acute stress.
 If a minor illness occurs or a surgical procedure is to be performed during
this period, the steroid taper should be suspended, and the steroid dosage
temporarily increased to the equivalent of 25 mg of prednisone
(hydrocortisone is a better choice in the preop setting because it can be
given IM or IV, in a dosage of approx. 100 mg bid)
 If the patient is under more intense stress, the dosage may have to be
increased to the equivalent of 250-300 mg of hydrocortisone per day to
mimic the normal adrenal response to stress.
 After the stress is resolved, the steroid is again taped and stabilized at a
dosage equivalent to 5 mg prednisone per day.
 The patient should remain on this physiologic replacement dosage (5 mg) for
4 weeks after the resolution of the acute stress or surgery.
 At this time, a direct challenge to the HPA axis can be performed through a
cosyntropic (Cortosyn) challenge.
 Performed any time of the day with need to fast
 Cosyntropin is administered IM, 25 U (0.25 mg, same as 250 mcg)
 The plasma cortisol level is measured just before and 30 minutes after the
injection.
 If the patient’s cortisol level is augmented by 6 mcg per dL and the peak
cortisol level is > 20 mcg per dL, the HPA axis has recovered and
exogenous steroid can safely be discontinued
 If the increase in cortisol is < 6 mcg per dL and/or the peak cortisol value
is < 20 mcg per dL, a slower steroid taper is recommended
 Stage 2: If the patient “failed” the corticotropin challenge, the HPA axis is
still suppressed.
 Prednisone should be continued and tapered slowly to a dosage of 5 mg
every other day, and the challenge should be retried.
 Stage 3: In cases of ambiguity or in patients with persistently poor
augmentation of plasma cortisol, other problems should be considered, such as
coexistent pituitary or adrenal disease, or an associated endocrinopathy
(hypothyroidism).
Diabetes Mellitus

Diabetes mellitus (DM) is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
 The chronic hyperglycemia of diabetes is associated with long-term damage,
dysfunction, and failure of various organs, especially the eyes, kidneys, nerves,
heart, and blood vessels.

Several pathogenic processes are involved in the development of DM. These range
from autoimmune destruction of the beta-cells of the pancreas with consequent
insulin-deficiency to abnormalities that result in resistance to insulin action.
 The basis of the abnormalities in carbohydrate, fat, and protein metabolism in DM
is deficient action of insulin on target tissues.
 Deficient insulin action results from inadequate insulin secretion and/or
diminished tissue responses to insulin at one or more points in the complex
pathways of hormone action.
Impairment of insulin secretion and defects in insulin action frequently coexist in the
same patient, and it is often unclear which abnormality, if either alone, is the primary
cause of the hyperglycemia. Thus, the reason for frequent use of multiple
medications in treatment of Type 2.

Type 1 (formerly insulin dependent, or IDDM):
 No production of insulin due to destruction of pancreas’ beta cells, thought to be a
result of genetically prone autoimmune response (immune mediated)
 Associated with Grave’s, Hashimoto’s, Addison’s
 Variable beta cell destruction (when down to 20% beta cells left, symptoms appear)
 Insulin-dependent
 Produces ketones with hyperglycemia
 Without insulin, will die (ketosis)
Type 2 (formerly noninsulin-dependent, or NIDDM):
 Minimal production of insulin due to hyperplastic beta cells (insulin deficiency)
 Insulin-resistant Type 2 is exacerbated by poorly responding insulin receptors, thus
requiring larger doses of insulin to respond.
 Rarely produces ketones with hyperglycemia
 7-8 million diagnosed/8 million undiagnosed
 Usual onset 8 years before diagnosis
 Usually > 40 years old, overweight
Diagnosis of Diabetes:
Symptomatic person (polyuria, polydipsia, or weight loss)
Random plasma glucose > or = 200 mg/dL (confirm with one of two other tests:
FPG or 2 hr PG
Asymptomatic person
FPG ≥ 126 mg/dL
2 hr PG ≥ 200 mg/dL
A1c ≥ 6.5%
NOTE: Pre-diabetes (increased risk of developing diabetes in the future) is indicated by
A1c of 5.7% - 6.4%
 In this range, the higher the percentage, the higher the risk for diabetes and
cardiovascular disease. Those over 6.0% (very high risk) need intensive
interventions and vigilant follow-up, emphasizes the American Diabetes
Association (ADA).
Source:
http://www.bing.com/images/search?q=image+of+a1c+ranges&qpvt=image+of+a1c+ran
ges&qpvt=image+of+a1c+ranges&FORM=IGRE#view=detail&id=28844D2D3CF0A13
980D5AFFF8F9EB333899A700C&selectedIndex=21
Diagnosis of Impaired Fasting Glucose
FPG of 100-125
Diagnosis of Impaired Glucose Tolerance
2 hour glucose ≥ 140, but < 200
 Usually only develops Type 2 DM

May be insulin requiring
Others:
Gestational diabetes
Secondary diabetes (secondary to pancreatic disease, endocrinopathies such as
acromegaly and Cushings, and drugs (steroid-induced)
Diabetes Control and complications Trial (DCCT) [1993]:
“Intensive therapy effectively delays the onset and decreases the progression of
diabetic complications.” (decreases risk 50-60%)
Tight control recommended for both Type 1 and 2.
80-120
< 140
80-120
< 7%
Treatment Goals
ac
2 hr pc
HS
Hgb A1c
Glycosylated hemoglobin (Hgb A1c)
Formula: Average glucose (mg/dL) = 28.7 X A1c – 46.7
6% = plasma glucose of 126
Each 1% increase in A1c = approx. increase of 30 mg in plasma glucose
Source:
http://www.bing.com/images/search?q=A1C+Chart+What+Should+It+Be&Form=IQFRDR#view=d
etail&id=77D8C83F7BF8834E3B160ADD06E5987DF7A03ABC&selectedIndex=21
Agents for Management of Type 2 Diabetes
Oral Medications
Insulin-Augmenting Agents (increase insulin production; used for impaired insulin
secretion)

Sulfonylureas
 Act by stimulating the release of insulin from functioning beta cells in the islets of
Langerhans in the pancreas
 There is some evidence that sulfonylureas also sensitize β-cells to glucose,
that they decrease the rate of hepatic glucose production, and increase insulin
receptor sensitivity..
 1st generation: Chlorpropamide (Diabinese), tolbutamide (Orinase, Tolinase)
 2nd generation: glyburide (Glynase, DiaBeta, Micronase), glipizide (Glucotrol)
 Shorter duration of action and shorter half-lives, which decrease frequency
and severity of side effects
 2 long-acting: glimepiride (Amaryl) and extended-release glipizide (Glucotrol
XL)
 Reduce HgbA1C 1-2%
 To minimize risk of hypoglycemia, starting dosage should be low (5 mg in adults,
2.5 mg in elderly)
 Should be taken with breakfast or the first main meal of the day to maximize
effect and safety
 ** Risk of hypoglycemia
 Educate patient regarding signs/symptoms and treatment of hypoglycemia
(should carry rapid-acting glucose source)
 Space meals no more than 4 hours apart; avoid missing meals
 Use of alcohol increases risk of hypoglycemia
 Beware of Sulfa allergies

Meglitinides
 Act by stimulating the release of insulin from functioning beta cells in the islets of
Langerhans in the pancreas
 Best suited for patients with type 2 diabetes who have high postprandial glucose
levels
 Repaglinide (Prandin), nateglinide (Starlix)
 Onset of action is 20-30 minutes; taken just prior to a meal; taken three times/day
 Risk of hypoglycemia
 If meal is not going to be consumed, the medication dose should also be skipped.
 Discuss importance of not skipping meals
 Reduce HgbA1C 1-2%
 Note: If adequate control is not achieved using a sulfonylurea agent, it is unlikely
that a glinide will be effective
Insulin-Assisting Agents

Biguanides (used for increased basal hepatic glucose production)
 Acts mainly on the liver
 Inhibits hepatic glycogenolysis and gluconeogenesis
 Improves insulin sensitivity in muscle and fat
 Reduces overnight glucose production by the liver and fasting
hyperglycemia
 Metformin (Glucophage, Glucophage XR) (at higher dosages, may reduce food
intake and help with weight control)
 Available in liquid form (Riomet)
 Also available in extended-release tablets (Fortamet, Glucophage XR)—Dose is
taken once daily, best with the evening meal
 Not metabolized; must be excreted by the kidney
 High levels of metformin can cause fatal lactic acidosis; cannot be used when
serum creatinine > 1.4 mg/dL in women or > 1.5 mg/dL in men.
 Precaution: Diagnostic studies with radiopaque dye
 Often causes nausea or diarrhea when first taken (in 5% of patients taking low
dosage and in 20-25% in those treated with a full dosage)
 Titrate the dose up to minimize GI side effects
 First-line therapy for DM2 (unless has renal dysfunction)
 Of benefit for obese patients….may have decreased appetite with metformin
 Also helps decrease triglycerides
 Reduce HgbA1C 1-2%
 Metformin can be quite effective in a dosage of 500 mg taken once daily before a
major meal (to maximize its satiety effect) or at bedtime (to control fasting
hyperglycemia)
 Can be titrated to 850 mg once daily, 500 mg twice daily, or higher (Max: 2550
mg/day)
 Patients should be instructed to stop taking metformin if they develop an illness
that causes dehydration or otherwise threatens renal clearance of this agent.
 Patients should be instructed to avoid excessive alcohol consumption while taking
metformin
 Associated with megaloblastic (Vitamin B12) deficiency: What is the
concern for patients with diabetes?

Alpha-glucosidase inhibitors (used to decrease GI absorption)
 Delay the digestion and absorption of complex carbohydrates in the small
intestine
 Ability to limit glucose increases after meals can reduce plasma insulin levels and
the need for injected insulin
 Acarbose (Precose) and miglitol (Glyset)
 Quite safe, but often cause flatulence, especially when dosage is increased rapidly
 Do not use in patients with significant intestinal disorders
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Best suited for patients with high postprandial glucose levels
Reduce HgbA1C 0.5-1%
Best started at a dosage of 25 mg taken once daily with a meal for two weeks;
then increased to 25 mg taken twice daily at meals for two more weeks, and
finally increased to 25 mg taken three times daily at meals; should be taken
immediately before the meal
Problem with compliance: must take with first bite of meal
Can have problems treating hypoglycemia because delays CHO absorption; treat
with simple sugar sources (glucose tablets or gel)
Need to monitor 2-hour postprandial blood glucose levels to identify effectiveness
of the therapy

Thiazolidinediones (used for decreased insulin-stimulated glucose uptake)
 Improve the response of muscle and adipose tissue to insulin in patients who are
otherwise relatively unresponsive, notably the extremely obese
 Pioglitazone (Actos), rosiglitazone (Avandia)
 ALT should be measured every 2 months for the first year, since unknown
whether there will be liver problems with these. (Rezulin was pulled from market
due to liver toxicity.)
 Patient education to report symptoms indicating possible liver problems:
unexplained N & V, abdominal pain, fatigue, anorexia, dark urine
 Reduce HgbA1C by 0.5-1.5%
 Weight gain most common side effect
 Risk of fluid retention and CHF. Contraindicated with NYHA Class III, IV heart
failure
 Patient education focus on identification of developing or worsening heart
failure: monitor weight daily and report any weight gain of 5 pounds or more
over a 2-day period
 Avandia associated with bone fractures in women, decreased efficacy of OCPs,
resumption of ovulation in premenopausal anovulatory women, potential
increased risk of heart failure

Dipeptidyl peptidase-4 (DPP-4) Inhibitor Therapy
 NORMALLY: two incretin hormones, glucogon-like peptide-1 (GLP-1) and
glucose-dependent insulinotropic polypeptide (GIP), both cause an increase in
insulin synthesis and release from pancreatic beta cells in response to normal or
increased blood glucose levels. When blood glucose concentrations are normal or
elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic
beta cells by intracellular signaling pathways involving cyclic adenosine
monophosphate.
 GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to
reduced hepatic glucose production.
 GLP-1 and GIP are released by the intestine throughout the day, and levels are
increased in response to a meal. These hormones are rapidly inactivated by DPP4.



Sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin
(Nesina) – as a DPP-4 inhibitor, slows the inactivation of incretin hormones, thus
increases insulin when glucose is increased, especially after eating
Once daily dosing; does not have to be taken with food
Sodium-glucose co-transporter-2 (SGLT2) inhibitor
 Lowers renal glucose threshold
 Results in increased urinary glucose excretion
 Examples: canaglifozin (Invokana), dapagliflozin (Farxiga), empagliflozin
(Jardiance)
 Dosing: Taken before first meal of the day
 Do not use if eGFR < 45 (canagliflozin, empaglifozin) or < 60 (dapagliflozin)
 What would you foresee as possible adverse effects of this type of
medication?
Combination Therapy
Because a single agent is unlikely to maintain glycemic control for more than a few
years, combination therapy is becoming quite common.
Principles:
 Combining drugs is usually more effective than stopping one agent and substituting
another
 Adding a second agent is usually better than increasing the dosage of an agent that is
already being given in a nearly maximum dosage
 Secondary failure of two-drug combinations should be expected eventually
Examples:
 Sulfonylurea and metformin
 Sulfonylurea and thiazolidinedione
 DDP-4 inhibitor and metformin
 SGLT2 inhibitor and metformin
Some commercially available combinations (see handout “Drugs for Type 2 Diabetes”
for additional examples):
 Actoplus Met = pioglitazone + metformin
 Avandamet = rosiglitazone + metformin
 Avandaryl = rosiglitazone + glimepiride
 Duetact = pioglitazone + glimepiride
 Glucovance = glyburide + metformin
 Janumet = sitaglipin + metformin
 Kombiglyze XR = saxagliptin + metformin
 Metaglip = glipizide + metformin
 Janumet = sitaglipin + metformin
 Invokamet = canagliflozin + metformin
In both ADA (American Diabetes Association) and AACE (American Association of
Clinical Endocrinologists) guidelines, three-drug combinations are included as options,
although cost is a consideration and there is increased risk of side effects. In some
patients, especially those with A1c > 8.5%, the failure of two oral agents used together
calls for the use of insulin alone or in addition to the oral agents.
Another interesting option:
DDP-4 inhibitor + anti-hyperlipidemic agent [sigagliptin (Januvia) + simvastation =
Juvisync]
Remember cost…..insurance companies do not pay for convenience! Also, think about
$4 or free medication plans!
Incretin Mimetics = Glucagon-like peptide-1 (GLP-1) agonists
GLP-1 is released by cells in the GI tract.
 Binds with and activates the GLP-1 receptor, which increases both synthesis and
secretion of insulin
 Other physiologic functions of GLP-1:
o Suppresses glucagon secretion from the pancreas
o Slows gastric emptying and food absorption
o Decreases food intake by increasing satiety in brain
Source: http://casesblog.blogspot.com/2006/11/dpp-4-inhibitors-for-treatment-of.html
With all GLP-1 agonists: not to be used in patients with a personal or family
history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) or medullary
thyroid carcinoma (MTC). Also, at risk of pancreatitis….check for presence of risk
factors (history of pancreatitis, gallstones, high triglycerides).
o Educate patients regarding s/sx of MTC (throat fullness, difficulty
swallowing, palpable lump in neck) and pancreatitis (severe abdominal
pain, N & V)
If administering GLP-1 agonist with insulin or insulin secretagogue (e.g. sulfonylurea),
dose of the insulin or secretagogue should be lowered to avoid hypoglycemia
Byetta (exenatide)
 Approved in 2005
 Synthetic version of exendin-4, a hormone found in the saliva of the Gila monster
(Heloderma suspectum lizard); biological properties similar to human GLP-1.
 Onset: 30 minutes; Duration: 10 hours
 Does not impair the normal glucagon response to hypoglycemia
 Comes in prefilled syringes (pens): 5 mcg and 10 mcg
 Dosing: 5 mcg subcu bid X 1 month, then increase to 10 mcg bid
o Up to 1 hours before meal
o Take before 2 largest meals (Must be at least 6 hours apart)
 Indicated for individuals who have not achieved adequate controls on
combination therapy
 Side effects: Nausea, vomiting, diarrhea, dizziness, headache, dyspepsia
o Can minimize nausea by deceasing time given before meal
o But get more benefit from extending out to the 1 hour before (weight loss
due to feeling of fullness)
Victoza (liraglutide)
 Approved in 2010
 Longer duration of action than Byetta, so Victoza given daily
o 0.6 mg. subcu daily X 1 week, then increase to 1.2 mg daily (maximum:
1.8 mg/day)
o Pen has markings for 0.6, 1.2, and 1.8 mg doses
 SE: headache, nausea, diarrhea
Bydureon (exenatide extended-release)
 Approved by FDA February 2012
 2 mg. subcutaneous once every seven days (weekly); any time of day and with or
without meals
o Delivered in biodegradable biospheres; may cause raised areas under skin
at injection site
 Decrease in A1C of 1.6%

SE: nausea, hypoglycemia, vomiting, diarrhea
Tanzeum (albiglutide)
 Approved by FDA in April 2014
 Dosing: 30 mg subcutaneously once weekly; may be increased to 50 mg once
weekly if glycemic response is inadequate.
 May be administered at any time of day without regard to meals
 Should be administered on same day each week. If need to change day, need to
have been 4 or more days since last dose.
Trulicity (dulaglutide)
 Approved by FDA in September 2014
 Dosing: 0.75 mg subcutaneously once weekly; may be increased to 1.5 mg once
weekly if glycemic response is inadequate
 May be administered at any time of day without regard to meals
 Trulicity pen requires no reconstitution; have no-see, no-handle needle
Amylin Analog
Amylin is a neuroendocrine hormone that contributes to glucose control during
postprandial period
Symlin (pramlintide) – (2005)
 Acts by promoting satiety, slowing gastric emptying, and decreasing postprandial
glucagon secretion
o Feeling of fullness  decreased caloric intake  weight loss
o Slowed gastric emptying  reduces initial postprandial increase in plasma
glucose
 Contraindicated: gastroparesis, with medications that affect GI motility
 SE: N, anorexia, dizziness, pharyngitis
o Greatest risk is hypoglycemia (can be severe with DM1 with insulin)
 Onset: 30 minutes; Duration: 3 hours
 Used for DM1 patient who uses bolus insulin at mealtime without optimum
control
o Dosing: 15 mcg before each meal; increase every 3 days in 15 mcg.
increments to a maximum of 60 mcg
 Used for DM2 patient who uses bolus insulin at mealtime without optimum
control, with or without concurrent sulfonylurea/Metformin
o Dosing: 60 mcg immediately before eating; can be titrated up to 120 mcg
after 3-7 days if needed
Insulins: Basal Insulins
Basal insulin refers to the steady background insulin that controls blood glucose levels in
the fasting state (overnight and between meals).
 For DM2, can be added to oral agents to achieve better glycemic control
NPH (Intermediate-Acting) Insulin
 Marketed as Novolin N or Humulin N
 Onset: 1-2 hours; peak effect within 4-14 hours
 May be prescribed once or twice a day
 “Intermediate-acting” since duration is longer than regular insulin or insulin
aspart but not as long as insulin glargine or determir.
 Concentration is 100 units/mL; usually cloudy or milky
 Synthesized using non-infectious E. coli bacteria
 Available in vials or pre-filled syringes
Insulin glargine
 Marketed as Lantus (since 2000)
 First long-acting recombinant human insulin analog
 Concentration is 100 units/mL; clear solution
 Available in vials, cartridges (OptiClik), or pens (SoloStar)
o Pens and cartridges 3 mL (total of 300 units)
Insulin detemir
 Marketed as Levemir
 Long-acting insulin analog; approved in 2005
 Available in vials or pens (3 mL = 300 units)
 Duration is 6-23 hours; mediated by slow absorption from the injection site and
slow distribution to target tissues due to a strong self-association and albumin
binding
Insulins: Bolus Insulins
Bolus insulin refers to the administration of a rapid-acting insulin, usually after ingestion
of carbohydrates (mealtime bolus) or in reaction to an elevated glucose level (correction
bolus, “sliding scale”).
 Can be administrated via single subcutaneous injections or via an insulin pump
 Mealtime bolus requires understanding of carb counting
Insulin aspart
 Marketed as Novolog
 Recombinant DNA (rDNA) origin; produced using baker’s yeast
 Rapid-acting; similar to regular human insulin

Available in 10 mL vials and 3 mL pens (100 units/mL)
Insulin lispro
 Marketed as Humalog
 rDNA origin; synthesized from nonpathogenic E. coli
 Available in vials and KwikPens
Insulin glulisine
 Marketed as Apidra
 rDNA origin; synthesized from nonpathogenic E. coli
 Available in vials and pens
Regular insulin
 Marketed as Humulin R and Novolin R
o Humulin R: Created in a nonpathogenic strain of E. coli
o Novolin R: structurally identical to natural human insulin; produced using
baker’s yeast
Comparative Action of Different Insulin Preparations
Insulin
Basal Insulins
NPH: Humulin N
Novolin N
Insulin glargine
(Lantus)***
Insulin determir
(Levemir)***
Onset
Peak
Duration
1-2 hours
4-14 hours
1 hour
No true peak
10- >24
hours
20-24 hours
1hour
No true peak
6-23 hours
Cost
10 mL vial:
$69.99
10 mL vial:
$118.99
5 - 3 mL pens:
$223.56
10 mL vial:
$120.44
Bolus Insulins
Insulin aspart
< 15 minutes 1-3 hours
3-5 hours
10 mL vial:
(Novolog)
$133.99
Insulin lispro
< 30 minutes 30-90 minutes < 6 hours
10 mL vial:
(Humalog)
$136.99
Insulin glulisine
< 30 minutes 30-90 minutes < 6 hours
3 mL pen: $47.99
(Apidra)
Regular: Humulin
0.5-1 hour
2-4 hours
6-12 hours
10 mL Vial:
R
$70.99
Novolin R
*** Should also use rapid- or short-acting insulin before each meal in type 1 DM; may
use with oral therapy or rapid- or short-acting insulin in type 2 DM; do not mix with
other insulins in same syringe.
Combination Insulin Preparations
 Various combinations available of NPH + rapid-acting insulins
 NOTE: insulins glargine and determir and injectable incretin mimetics and
amylin analogs CANNOT be mixed in the same syringes with additional insulin
formulations
 Used to achieve greater efficacy, coverage, and accuracy with fewer injections
 Available in vials or pens
 Available combinations:
o Humulin or Novolin 70/30 (70% NPH and 30% regular insulin)
o Humulin 50/50 (50% NPH and 50% regular insulin)
o Humalog 75/25 (75% NPH and 25% insulin lispro)
o Novolog 70/30 (70% NPH and 30% insulin aspart)
General info regarding insulin storage/use:
 Unopened vials/pens should be stored in the refrigerator, best in the door to avoid
possible freezing
 After opening, must be used within 28 days
 After removal from refrigerator, allow to warm to room temperature before using
(better absorption, more comfortable injection)
Factors affecting absorption of subcutaneous insulin: What would be the effect of each
of these on absorption?
 Lipohypertrophy
 Anatomical area
 Exercise
 Size of dose
CAUTION: Gastroparesis = autonomic neuropathy – affects stomach (food stays in the
stomach, instead of being absorbed in 2 hours). Food is still in stomach after 12 hours. If
given insulin  hypoglycemia.
Basic Guidelines
AM – NPH
affects
SUPPER
AM – Regular affects
NOON
PM – NPH
NEXT MORNING
affects
PM – Regular affects
BEDTIME
Inhaled Insulin
 Approved by FDA in June 2014
 Afrezza: a rapid-acting inhaled insulin approved for improving glycemic control
in adults with type 1 and type 2 diabetes
 Administered prior to meals or within 20 minutes of starting a meal
 Peak insulin levels within 12-15 minutes of administration
 Not a substitute for long-acting insulin and must be used in combination with
long-acting insulin in patients with type 1 diabetes.
 Not recommended for treatment of diabetic ketoacidosis
 Contraindicated in patients with asthma or COPD (due to risk of acute
bronchospasm)
 Not recommended in patients who smoke or who have recently stopped smoking
 Most common adverse reactions: hypoglycemia, cough, throat pain or irritation
 Perform spirometry prior to beginning Afrezza, 6 months after starting it, and then
each year after that. Consider discontinuing Afrezza in patients with a decline of
greater than or equal to 20% in FEV1 from baseline
 Available in 4 and 8-unit dry powder cartridges (see Figure 1 below for
conversion from injectable to inhaled mealtime insulin)
Source:
http://www.bing.com/images/search?q=image+of+afrezza+dosing&id=6705607A224430E334F99
0A393730746028B5D96&FORM=IQFRBA#view=detail&id=6705607A224430E334F990A393730
746028B5D96&selectedIndex=0
Source:
http://www.bing.com/images/search?q=A1C+Chart+What+Should+It+Be&Form=IQFR
DR#view=detail&id=E165569E36ACB5A36C9392E93D956F0E8BF79866&selectedInd
ex=46