NRG 202: WEEK 6

DRUGS FOR DIABETES MELLITUS

Topics to be discussed:

⮚ Background on Diabetes Mellitus

⮚ Insulin
o Types
o Preparation ⮚ polyuria — increased urination
o Administration
o Storage ⮚ secondary failure - a gradual increase in blood
o Health Teachings sugar levels that can be caused by an increase in
the severity of diabetes or a decreased response
⮚ Oral Hypoglycemic Agents
to a drug
o Biguanides
o Sulfonylureas
o Thiazolidinediones
o DDP-4 Inhibitors
o Sodium-glucose Co-transfer Inhibitors
KEY TERMS INSULIN

⮚ diabetes mellitus — a chronic disorder

characterized either by insufficient insulin
production in the b-cells of the pancreas or by
cellular resistance to insulin
⮚ diabetic ketoacidosis — a potentially
life-threatening deficiency of insulin
(hypoinsulinism), resulting in severe
hyperglycemia and requiring prompt diagnosis
and treatment
⮚ glucagon — a hormone produced by the a-cells
of the pancreas that increases blood sugar by
stimulating the conversion of glycogen to
glucose in the liver
⮚ glucometer — a device used to monitor blood
glucose levels
⮚ hyperglycemia — elevated blood glucose level

⮚ hypoglycemia — low blood glucose level

⮚ insulin — a hormone produced by the pancreas

that helps maintain blood glucose levels within
⮚ normal limits lipodystrophy — atrophy of
subcutaneous fat
⮚ polydipsia — increased thirst

⮚ polyphagia — increased appetite

 There are two major types of diabetes mellitus:
⮚ Insulin, a hormone produced by the pancreas,
acts to maintain blood glucose levels within ⮚ Type 1 (Formerly known as insulin-dependent
normal limits.
diabetes mellitus, juvenile diabetes,
⮚ This is accomplished by the release of small juvenile-onset diabetes, and brittle diabetes)
amounts of insulin into the bloodstream ⮚ Type 2 (Formerly known as
throughout the day in response to changes in
blood glucose levels. non-insulin-dependent diabetes mellitus,
maturity-onset diabetes, adult-onset diabetes,
⮚ Insulin is essential for using glucose in cellular and stable diabetes)
metabolism and for the metabolism of protein
and fat.

Type 1 Diabetes

⮚ Produce insulin in insufficient amounts and

therefore must have insulin supplementation to
survive.
⮚ usually has a rapid onset, occurs before the age
of 20 years
⮚ produces more severe symptoms than type 2
Diabetes Mellitus
diabetes
⮚ Diabetes mellitus is a ⮚ More difficult to control.
complicated, chronic disorder
characterized either by Major symptom:
insufficient insulin production
in the b-cells of the pancreas or ⮚ hyperglycemia
by cellular resistance to insulin. ⮚ polydipsia (increased thirst)
⮚ Insulin insufficiency results in elevated blood
⮚ polyphagia (increased appetite)
glucose levels or hyperglycemia.
⮚ polyuria (increased urination)
⮚ Individuals with diabetes are at greater risk for a
number of disorders, including myocardial ⮚ weight loss
infarction, cerebrovascular accident (stroke),
blindness, kidney disease, and lower limb Treatment requires a strict regimen that typically
amputations. includes a carefully calculated diet, planned physical
activity, home glucose testing several times per day, and
⮚ Insulin and the oral antidiabetic drugs, along with multiple daily insulin injections.
diet and exercise, are the cornerstones of treatment
for diabetes mellitus.
⮚ They are used to prevent episodes of
hyperglycemia and to normalize carbohydrate
metabolism
Type 2 Diabetes Obesity is thought to contribute to type 2 diabetes by
placing additional stress on the pancreas, which makes
⮚ Approximately 90% to 95% of adults with it less able to respond and produce adequate insulin to
diabetes have type 2. meet the body’s metabolic needs.

⮚ Those with type 2 either have a decreased Many individuals with type 2 diabetes are able to
production of insulin by the b-cells of the control the disorder with diet, exercise, and
pancreas or have a decreased sensitivity of the
cells to insulin, making the cells insulin
resistant.
⮚ Although type 2 diabetes may occur at any age,
the disorder occurs most often after the age of
40 years.
⮚ The onset of type 2 diabetes is usually insidious,
and the symptoms are less severe than in type
1 diabetes mellitus. Because it tends to be more antidiabetic drugs.
stable, it is easier to control than type 1
diabetes. However, approximately
Risk factors include:

⮚ Obesity

⮚ Older age

⮚ Family history of diabetes

⮚ History of gestational diabetes (diabetes that

develops during pregnancy but disappears
when pregnancy is over)
⮚ Impaired glucose tolerance

⮚ Minimal or no physical activity

⮚ Race/ethnicity (more common in blacks,

Hispanic/Latino Americans, American Indians,

However, approximately 40% of those with type 2

diabetes do not have a good response to the

antidiabetic drugs and require the addition of insulin to

and some Asian Americans) control the diabetes.

Insulin was originally developed from purified extracts
from beef and pork pancreas because it was biologically
similar to human insulin. However, these animal-source
insulins are no longer used today. Synthetic insulins,
including human insulin or insulin analogs, have
replaced them.
Actions of Insulin
Insulin appears to activate a process that helps glucose
molecules enter the cells of striated muscle and adipose
tissue.
Insulin also stimulates the synthesis of glycogen by the
liver. In addition, insulin promotes protein synthesis and
helps the body store fat by preventing its breakdown for
energy.
Insulin Preparations Various insulin
Various insulin preparations have been developed with
a more gradual onset and prolonged duration of effect.
Insulin preparations are classified as rapid-acting, short
acting, intermediate-acting, or long acting
Uses of Insulin
Insulin is necessary for controlling type 1 diabetes that
is caused by a marked decrease in the amount of insulin
produced by the pancreas.
Insulin is also used to control the more severe and
complicated forms of type 2 diabetes. However, many
patients can control type 2 diabetes with diet and
exercise alone or with diet, exercise, and an antidiabetic
drug
Insulin may also be used in the treatment of severe
diabetic ketoacidosis (a type of metabolic acidosis
caused by an accumulation of ketone bodies in the
blood) or diabetic coma.
Insulin is also used in combination with glucose to treat
hypokalemia by shifting potassium from the blood into
the cells.
Adverse Reactions of Insulin
The two major adverse reactions seen with insulin
administration are hypoglycemia (low blood glucose or
sugar) and hyperglycemia (elevated blood glucose or
sugar).
Hypoglycemia may occur when there is too much
insulin in the bloodstream in relation to the available
glucose (hyperinsulinism).
Hypoglycemia may occur:
 ⮚ When the patient eats too little food

⮚ When the insulin dose is incorrectly measured

and is greater than that prescribed
⮚ When the patient drastically increases physical
activity
Hyperglycemia may occur if there is too little insulin in
the bloodstream in relation to the available glucose
(hypoinsulinism).
Hyperglycemia may occur

⮚ When the patient eats too much food

⮚ When too little or no insulin is used ⮚ Glucose 10% or 50% via intravenous route
⮚ When the patient experiences emotional stress,
infection, surgery, pregnancy, or an acute illness
Contraindications, Precautions, and Interactions of
Hypoglycemic Reactions Insulin
Close observation of a patient with diabetes is ⮚ hypersensitivity
important, especially when diabetes is newly diagnosed,
the insulin dosage is changed, or the patient is ⮚ liver or kidney disease
pregnant, has a medical illness or has had surgery, or
fails to adhere to the prescribed diet. ⮚ Insulin appears to inhibit milk production in
lactating women and could interfere with
Episodes of hypoglycemia are corrected as soon as the
breast-feeding.
symptoms are recognized.
*Lactating women may require adjustment of their
insulin dose and diet.
Following are some drugs that decrease the
Methods of ending a hypoglycemic reaction include ypoglycemic effect of insulin:
taking one or more of the following:
⮚ AIDS antivirals
⮚ Orange juice or other fruit juice
⮚ Albuterol
⮚ Hard candy or honey
⮚ Contraceptives, oral
⮚ Commercial glucose products
⮚ Corticosteroids
⮚ Glucagon by the subcutaneous, intramuscular, or
⮚ Diltiazem
intravenous route
⮚ Diuretics

⮚ Dobutamine

⮚ Epinephrine

⮚ Estrogens

⮚ Lithium

⮚ Morphine sulfate
 ⮚ Niacin ✔ Your health care provider will teach you how to hold
the syringe, how to prepare insulin and how to
⮚ Phenothiazines
administer.
⮚ Thyroid hormones ✔ Insulin needs may change if you become ill,
especially with vomiting or fever and during periods
of stress or emotional disturbances. Contact your
Following are some drugs that increase the health care provider if these situations occur.
hypoglycemic effect of insulin:
✔ It is important that you follow the prescribed diet,
⮚ Alcohol and planning of daily menus.
✔ It is important to carry an extra supply of insulin
⮚ Angiotensin-converting enzyme inhibitors
and a prescription for needles and syringes
⮚ Antidiabetic drugs, oral especially when travelling.
⮚ b–Blocking drugs ✔ Report signs and symptoms of hypoglycemia and
hyperglycemia, notifying your health care provider
⮚ Calcium
immediately if either reaction occurs.
⮚ Clonidine ✔ Good skin and foot care, personal cleanliness,
⮚ Disopyramide frequent dental checkups, and routine eye
examinations are an important part of treating
⮚ Lithium diabetes.
⮚ Monoamine oxidase inhibitors (MAOIs) ✔ Follow your health care provider’s
recommendations regarding physical activity.
⮚ Salicylates
✔ Notify your health care provider if you have an
⮚ Sulfonamides increase in blood glucose levels, if you become
⮚ Tetracycline pregnant, if you have an occurrence of antidiabetic
or hyperglycemic episodes, or if you have an illness,
Educating the Patient and Family about Insulin infection, or diarrhea (your insulin dosage may
require adjustment).
Noncompliance is a problem in some patients with
diabetes, making patient and family teaching vital to the ✔ Tell your health care provider about any new
proper management of diabetes. problems (e.g., leg ulcers, numbness of the
extremities, significant weight gain or loss).
✔ Use the home test method recommended by your ✔ Wear identification, such as a medical alert tag, to
health care provider for blood glucose. Review the inform medical personnel and others that you use
instructions included with the glucometer. insulin to control the disease.
✔ Use only the recommended type, source, and brand
Antidiabetic Drugs
name of insulin. Do not change brands unless your
health care provider approves, and keep a spare Antidiabetic drugs are used to treat patients with type 2
vial on hand. diabetes that is not controlled by diet and exercise
alone.
✔ Keep your insulin at room temperature, away from
heat and direct sunlight, and dispose the vial within These drugs are not effective for treating type 1
1 month of first puncturing. Store vials not in use in diabetes.
the refrigerator. 1. Biguanides
✔ Be certain to purchase the same brand and needle 2. Sulfonylureas
size each time. 3. Thiazolidinediones
4. Dipeptidyl peptidase-4 inhibitor
5. Sodium-glucose Co-transporter 2 Inhibitors
1. BIGUANIDES
✔ Metformin use is temporarily discontinued for
MOA: glucose production and increasing insulin surgical procedures. The drug therapy is restarted
when a patient’s oral intake has been resumed and
sensitivity in muscle and fat cells.
renal function is normal.

The liver normally releases ✔ Risk of acute renal failure when iodinated contrast
glucose by detecting the level of material used for radiological studies is
circulating insulin. administered with metformin. Metformin therapy
is stopped for 48 hours before and after
When insulin levels are high, glucose is available in the
radiological studies using iodinated material.
blood and the liver produces little or no glucose.
✔ Alcohol, amiloride, digoxin, morphine,
When insulin levels are low, there is little circulating
procainamide, quinidine, quinine, ranitidine,
glucose, so the liver produces more glucose.
triamterene, trimethoprim, vancomycin,
In type 2 diabetes, the liver may not detect levels of cimetidine, and furosemide all increase the risk of
glucose in the blood and, instead of regulating glucose hypoglycemia.
production, releases glucose despite blood sugar levels. ✔ There is an increased risk of lactic acidosis when
Metformin (Glucophage) metformin is administered with the
glucocorticoids.
⮚ only biguanide currently available in most
2. SULFONYLUREAS
countries
MOA: stimulates the b-cells of the pancreas to release
⮚ sensitizes the liver to circulating insulin levels and insulin
reduces hepatic glucose production
The sulfonylureas are not effective if the b-cells of the
pancreas are unable to release a sufficient amount of
insulin to meet a patient’s needs.
The first-generation sulfonylureas are not commonly
used today because they have a long duration of action
CONTRAINDICATIONS: and a higher incidence of adverse reactions and are
more likely to react with other drugs.
Heart failure, renal disease, hypersensitivity, acute or
chronic metabolic acidosis, including ketoacidosis, older More commonly used sulfonylureas are the second- and
than age 80 and lactation. third-generation drugs.

Adverse Reactions:

⮚ asthenia (weakness, fatigue or tiredness)

⮚ headache

⮚ gastrointestinal upset (abdominal bloating, nausea,

cramping, diarrhea, flatulence, vomiting,
indigestion)
These adverse reactions are self- limiting and can be
reduced if a patient is started on a low dose and the
dosage increases slowly, and if the drug is taken with
meals.
Hypoglycemia rarely occurs when metformin is used
alone.
Precautions, and Interactions of Antidiabetic Drugs
 fluconazole, histamine H2 antagonists, methyldopa,
MAOIs, salicylates, sulfonamides, and tricyclic
antidepressants.
✔ The hypoglycemic effect of the sulfonylureas may be
decreased when the agents are administered with
bblockers, calcium channel blockers,
cholestyramine, corticosteroids, estrogens,
hydantoins, isoniazid, oral contraceptives,
phenothiazines, thiazide diuretics, and thyroid
agents
3. THIAZOLIDINEDIONES
MOA: also called GLITAZONES, decrease insulin
resistance and increase insulin sensitivity by modifying
several processes, with the end result being decreasing
hepatic glucogenesis (formation of glucose from
CONTRAINDICATIONS:
glycogen) and increasing insulin-dependent muscle
First Gen: (chlorpropamide, tolazamide, and glucose uptake
tolbutamide) are contraindicated in patients with
Adverse Reactions:
coronary artery disease or liver or renal dysfunction.
Adverse Reactions: ⮚ Aggravated diabetes mellitus

⮚ hypoglycemia ⮚ upper respiratory infections

⮚ Nausea and vomiting ⮚ sinusitis

⮚ epigastric discomfort ⮚ headache

⮚ heartburn ⮚ pharyngitis

⮚ myalgia
Often, these can be eliminated by reducing the dosage
or by giving the drug in divided doses. ⮚ diarrhea
If these reactions become severe, then the health care ⮚ back pain
provider may try another antidiabetic drug or
discontinue the use of these drugs. If the drug therapy is When used alone, rosiglitazone and pioglitazone rarely
discontinued, then it may be necessary to control the cause hypoglycemia. However, patients receiving these
diabetes with insulin. drugs in combination with insulin or other hypoglycemic
(e.g., sulfonylureas) are at greater risk for hypoglycemia.
Precautions, and Interactions of Antidiabetic Drugs
A reduction in the dosage of insulin or the sulfonylurea
✔ Used cautiously in patients with impaired liver may be required to prevent episodes of hypoglycemia.
function because liver dysfunction can prolong the In some patients, thiazolidinediones may cause or
drug’s effect exacerbate congestive heart failure.
✔ Used cautiously in patients with renal impairment
and severe cardiovascular disease
✔ There is a risk for cross-sensitivity with the
sulfonylureas and the sulfonamides.
✔ The sulfonylureas may have an increased
hypoglycemic effect when administered with the
anticoagulants, chloramphenicol, clofibrate,
 CONTRAINDICATIONS:
- hypersensitivity, severe heart failure
⮚ The thiazolidinediones are used cautiously in
patients with edema, cardiovascular disease, and
liver or kidney disease.
⮚ These drugs may alter the effects of oral
The thiazolidinediones are contraindicated in patients
with a known hypersensitivity to any component of the
drug and in patients with severe heart failure.
The thiazolidinediones are used cautiously in patients
with edema, cardiovascular disease, and liver or kidney
disease.
These drugs may alter the effects of oral contraceptives.
Patient Management:

The thiazolidinediones, pioglitazone and rosiglitazone,

are given with or without meals. If the dose is missed at
the usual meal, then the drug is taken at the next meal.
Once the drug is taken, the meal should not be delayed.
Delay of a meal for as little as 30 minutes can cause
hypoglycemia.
4. DIPEPTIDYL PEPTIDASE-4 INHIBITOR
MOA:
⮚ An enzyme in the body that breaks down incretin
hormones, which results in increased levels of
active incretin (released after eating and augment
the secretion of insulin released from pancreatic
beta cells)
⮚ The dipeptidyl peptidase-4 inhibitors prevent the
metabolism of the incretin hormones. The result
of increased incretin hormones is an increase in
insulin secretion and a decrease in glucagon
secretion.
Adverse Reactions:
⮚ nasopharyngitis
⮚ hypoglycemia
In addition, saxagliptin and sitagliptin both cause
headache, upper respiratory tract infections, and
headache
contraceptives.
5. SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS
MOA:
⮚ a new group of oral medications used for
treating type 2 diabetes
⮚ prevents the kidneys from reabsorbing glucose
back into the blood which allows the kidneys to
lower blood glucose levels and the excess
glucose in the blood is removed from the body
via urine.
The kidneys work by filtering glucose out of the blood
and then reabsorbing glucose back into the blood. The
proteins that reabsorb glucose are called
sodium-glucose transport proteins.
SGLT2 inhibitors block these proteins which means less
glucose gets reabsorbed back into the blood and gets
passed out of the body via the urine.
 ✔ Perform moderate exercise; avoid strenuous
SGLT2 inhibitors may be suitable for people with type 2 exercise and erratic periods of exercise.
diabetes that have high blood glucose levels despite
✔ Wear identification, such as a medical alert tag, to
being on a medication regimen such as metformin and
insulin. inform medical personnel and others of your
diabetes and the drug or drugs you currently use to
SE: UTI, hypoglycemia, diabetic acidosis treat the disease.
✔ Notify your health care provider if you experience
any of the following: episodes of hypoglycemia,
apparent symptoms of hyperglycemia, elevated
blood glucose levels, and positive results of urine
tests for glucose or ketone bodies, or pregnancy.
✔ Know the symptoms of hypoglycemia and
hyperglycemia and your health care provider’s
recommended method for terminating a
hypoglycemic reaction.
✔ Metformin: there is a risk of lactic acidosis when
you use this drug. Discontinue the drug therapy
and notify your health care provider immediately if
Educating the Patient and Family about Antidiabetic you experience any of the following: respiratory
Drugs distress, muscular aches, unusual difficulty
sleeping, unexplained malaise, or nonspecific
✔ Take the drug exactly as directed on the container, abdominal distress.
for example, with food or 30 minutes before a
meal.
✔ To control your diabetes, follow exactly the diet
and drug regimen prescribed by your health care
provider.
✔ Never stop taking this drug or increase or decrease
the dose unless told to do so by your health care
provider.
✔ Take the drug at the same time or times each day.

✔ Eat meals at approximately the same time each

day. Erratic meal hours or skipped meals may cause
you to have difficulty in controlling diabetes with
this drug.
✔ Avoid alcohol, dieting, commercial weight-loss
products, and strenuous exercise programs unless
your health care provider has approved.
✔ Test your blood for glucose and urine for ketones
as directed by your health care provider. Keep a
record of your test results and bring this record to
each visit to your health care provider.
✔ Maintain good foot and skin care and have routine
eye and dental examinations for the early
detection of any complications that may occur.