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Combination Therapy Instructor’s Notes
(some slides do not have written notations)
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Combination therapy may be defined as taking
more than one medication to control blood glucose.
It may be a combination of oral agents, or oral
agents and injectable medication such as exenatide
(Byetta®) or Insulin.
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Ninety percent of the people diagnosed with
diabetes, have type 2 diabetes.
Glucose is unable to enter the cells because the
endogenous insulin made is inefficient and does not
respond as quickly as it should. Over time, the
pancreas is not able to keep up with the body’s
needs for insulin. These two factors combined
result in elevated blood glucose.
The United Kingdom Prospective Diabetes Study
Group (UKPDS) confirmed the progressive nature
of type 2 diabetes.
Slide 4
Insulin resistance is related to obesity, usually due
to a sedentary lifestyle.
Initially, people with diabetes will make more insulin
than usual, but its action is ineffective.
Over time the pancreas will become stressed from
making an excessive amount of insulin and trying to
keep up with body’s needs.
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Phases of Fuel Homeostasis:
Phase I: The Fed State (0 to 4 hours after eating).
Circulating glucose comes from food ingested.
Insulin is released, glucagon levels are low and
triglycerides are synthesized by the liver and
adipose tissue. Insulin inhibits the breakdown of
glycogen and triglyceride reservoirs. The brain and
muscle use glucose, the rest is stored in the liver,
muscle, fat and other tissues.
Phase 2: Post-absorptive state (4 to 15.9 hours
later). The blood glucose comes from the glycogen
breakdown and hepatic gluconeogenesis. Insulin
levels decrease and glucagon levels increase.
Carbohydrate and lipid stores are available for use.
Liver glycogen breakdown provides a supply of
glucose to the brain and other tissues.
Phase 3: Early Starvation State Phase (16 to 48
hours later): blood glucose is supplied by hepatic
gluconeogenesis.
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Stepped approach requires that the treatment plan
evolve as needed to meet individual target blood
glucose goals. This means that the patient begins
an organized pattern of management. The patient
will progress to the next step when the current
therapy is no longer achieving the target blood
glucose goals.
This approach consists of four steps:
Step 1. An individualized meal plan and regular
exercise program is initiated to reduce insulin
resistance and lower blood glucose.
Historically, doctors have started patients on a
single oral medicine – often metformin - and then
added other medications when needed. Today,
more doctors may start patients on combination
therapy.
Step 2. Oral hypogglycemic agents are introduced,
in the combination required to meet goals. The
meal planning and exercise plan remain important
components of the treatment plan.
Slide 8
Step 3. Incretin Mimetics may be added to improve
blood glucose when target goals can no longer be
achieved.
Step 4. Insulin therapy is initiated when steps 1-3
are no longer achieving target levels.
Slide 9
Monitoring blood glucose before breakfast will tell
how effective the medication has been in controlling
blood glucose that increases during the night,
primarily from the release of glucose from the liver,
but also as a result of the snack eaten the evening
before.
Monitoring blood glucose 2 hours after a meal will
tell how effective the medication is in lowering the
blood glucose that has risen in response to the food
that you have eaten.
A1c: Provides a three month average of blood
glucose control. If the A1C is less than 7%, the
medication regimen is providing an acceptable level
of blood glucose control.
Slide 10
These are the current ADA treatment target goals
for blood glucose levels.
It is helpful to remember that a normal person’s
blood glucose levels are around 70-100 before
breakfast (fasting), similar before other meals, and
usually do not exceed 140 mg/dL at their peak, 2
hours after a meal.
Slide 11
The blood glucose was “in target” before the meal,
but “out of target” 2 hours after the meal. This may
be because:
•
The food eaten was a poor choice; changes
should be made to the meal plan.
•
The food portion was too large; a smaller
serving should be planned next time.
•
The medication is not enough to cover the
carbohydrate (carb) content of the meal.
Three of the items eaten have a high carbohydrate
(carb) content (potatoes, bread, juice). They may
have caused the blood glucose level to rise higher
than expected.
If this amount of carb is part of the meal plan, the
medication may have to be adjusted so that the
post-meal blood glucose stays in target. Otherwise,
lowering the amount of carb at dinner would be
helpful
Slide 12
Several classes of oral anti-hyperglycemic agents
are available today. Each works differently to control
blood glucose.
Because of their different types of action, they can
be combined for a maximum effect of lowering
blood glucose.
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A person taking a biguanide in combination with a
sulfonylurea may experience hypoglycemia
because of the action of the sulfonylurea.
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Not often used because of gastrointestinal side
effects
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People have many concerns about going on insulin.
It is important to explore these reasons and correct
any misconceptions they may have.
Slide 26
Once blood glucose levels normalize, most people
will report a better sense of well being and feeling
much more energetic. They often report that they
didn’t realize how tired they were until they started
to feel better.
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United Kingdom Prospective Diabetes Study Group:
Quality of Life in Type 2 Diabetic Patients is
Affected by Complications, But Not by Intensive
Policies to Improve Blood Glucose or Blood
Pressure Control. Diabetes Care (1999) 42:120121.
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