Menurunkan kadar gula darah dengan kriteria ADA2000

1
Menurunkan kadar gula darahdengan kriteria
ADA-2000

• Iwan Darmansjah
• PUKO, Pusat Uji Klinik Obat, FKUI

Updated 11 Sept 2002
2
Oral Antidiabetics (binds on different receptors)

• Sulfonylureas 1st generation
• chlorpropamide (Diabinese)
• 2nd generation glibenclamide (Daonil)
• glipizide (Minidiab)
• gliclazide (Diamicron)
• glimepiride (Amaryl)
• Newer OADs metformin (Glucophage)
  (mechanism) acarbose (Glucobay)
  repaglinide (NovoNorm) pioglitazone
  (Actos)

3
(No Transcript)
4
(No Transcript)
5
In obese patients

• Try metformin first.
• Shown to reduce diabetic events and mortality.
• Side effect lactic acidosis - rare but fatal -
• (anorexia, vomiting, abdominal pain, cramps,
  malaise, weight loss)
• Contra-indicated renal and hepatic impairment,
  heart failure, specially in old age.

6
In non-obese NIDDM patients

• Of the sulfonylureas glibenclamide has the best
  data to significantly reduce the incidence of
  diabetes-related events.
• Gliclacide and glipizide lacks long term data.
• Chlorpropamide is not recommended.
• Repaglinide is short acting and should be given
  before each meal. Fit for patients with erratic
  eating times.

(2000 Australian Medicines Handbook)
7
Strategy of diabetic management (1)

• A thorough history-taking is pivotal
• How is life-style? Highlight eating habits!
• eating times, restaurants, snacks, bowel
  movements, etc.
• What is the patient eating and drinking during 24
  hrs. How much?
• What are the foods drinks he/she likes?
• Interview the spouse too.
• Take complete drug history, Lab. data.
• Spend 30 min. on first visit.

8
Strategy of diabetic management (2)

• Strict blood glucose control, but ...
• no hypoglycaemic bouts allowed!
• Through diet first,. then exercise.
• Understand OAD profile you are using, such as
  kinetics and dosing.
• No meal, no drug!

9
Diet is most important

• But, strict diabetic diet is difficult to
  perform.
• Do not add sugar to food . but no special diet
  needed.
• Three (preferably) small main meals with snacks
  in between and before going to bed.
• Not understanding which food is contributing to
  high blood sugar, like donated foods by loving
  people.

10
Food-watch Indonesia

• Coca-cola, Fanta, Sprite, Teh Botol, beer,
  condensed milk, and the like total ban!
• Jajan pasar, snack, cakes, singkong, tape, kecap
  manis should be very limited.
• Life-style foods drinks, such as energy drinks,
  some dietary supplements may be diabetogenic.
  Check sugar content!
• Fruits (despite popular belief) manggo, durian,
  grapes, rambutan, water-melon, nangka, sawo, also
  canned fruit in syrup. Fructose becomes glucose,
  although at slower rate.

11
Special attention for difficult patients

• Erratic eating times
• late or no breakfast, 1- gt3 times/day, continuous
  eating
• Variation of caloric intake
• busy people, certain professions, eating out
  daily
• Non-compliance of treatment schedules.
• Sweet-toothed patients.

12
American Diabetes Assoc. Criteria DIABETES CARE
2000 (adapted)
Depending on Assay norms
13
HbA1c is glycosylated Hb of the RBC and is the
result of

• Fasting bl.glucose
• Hepatic gl. production
• Hepatic sensitivity
• to insulin

• Postprandial glucose
• Preprandial gl.
• Insulin secretion
• Glucose load from meal
• Insulin sensitivity in peripheral tissues.

Check glycoHb once every 3-4 months
14
False Interpretation of Fasting bl.gl. value

• FBG value may be high due to timing of
  determination that exceeds the duration of action
  of the drug.

Lab. determinination
Drug effect ends
Insulin injection
24 hrs
0 hrs
15
WHAT ACTIONS?

• Dietary counseling.
• When checking bl.gl. OAD must be taken as usual
  (before breakfast).
• Adjust drug treatment
• up/down regulation of insulin dose or timing
• assess OAD used type and dosing schedule
• consider whether adding another OAD with
  different mechanism would improve.
• allow some higher glucose goal levels in frail,
  old, debilitated subjects.

16
Sulfonylureas hypoglycemic risk

RR
Tolbutamide Gliclazide Repaglinide Glipizide Glime
piride Glibenclamide
1 1 - 2(2) 1 - 2 2(1) 3 - 4(3) 5(1)
1) Ferner 1988 (2) Teisse, Diab Med,1994 (3)
Dills, Horm Metab Res,1996
17
Hypoglycemic risk

• Glibenclamide has greatest risk for hypoglycemia
  (less so when given 2-3 times a day in smaller
  portions)
• Repaglinide (3 times a day) seems to have
  smallest risk, but needs more confirmation on its
  efficacy in severe DM.
• Although different receptor-binding explains
  this difference, the small doses used is crucial.

18
Hypoglycemic risk is

• Almost absent with
• metformin
• troglitazones
• acarbose
• Low with
• repaglinide
• glipizide slow-relased

But, their hypoglycemic potency is low. As an
add-on to insulin or more potent sulfonylureas
it forms a useful buffer against hypoglycemias.
19
What patients do not tell their doctor

• Many patients experience hypoglycemia at around 3
  - 5 hours after dosing of glibenclamide.
• Feeling of hunger results in extra food intake
  and sweet drink, followed by blood glucose
  increase.
• Doctor inadvertently prescribe higher dose of
  OAD, resulting in more hypoglycemic bouts. Some
  patients stop their drugs.

20
Hunger feeling createshypoglycemic angst

• Can be low or high bl.sugar.
• When in doubt, check bl.glucose at that time
  (about 1100 AM or bed-time).
• When bl.gl. is within gt80 - 140 mg, dont take
  large snack, but wait for regular meal-time.

21
Hypo-Hyper Phenomenon
Glibenclamid OD Morning dose
More drug prescribed
Hypoglycemia 3-5 hrs post-dose
Feeling of hunger
Hyperglycemia increased (fasting, PP, and HbA1c)
Eat and drink (sweet) extra
(I. Darmansjah)
22
Dosing Principle of Sulfonylureas

• Small divided doses before meals better than
  large single morning dose (hypoglycemic riskgt).
• Obtain day curve for 2-3 days (with or without
  OAD).
• Follow up closely once weekly.
• Start with one OAD and monitor bl gl by day curve
  (observe which value is exceeded).
• If far from goal (gt8.0), add another OAD
  (preferredmetformin, repaglinide, acarbose, or
  pioglitazone, when not contra-indicated).

23
HbA1c10.1
24
(No Transcript)
25
With constant follow up.
26
Dosing schedule of second generation
sulfonylureas should be revised

• Some sulfonylureas (especially glibenclamide)
  have been given in single daily doses to prolong
  action, increase ease, and compliance.............
  .
• They are prone to cause hypoglycemia
• divided doses (bid or tid) is better.
• Occasionally it results in coma and death.

(Darmansjah Med J Univ Indon 1994 3 122-123)
27
Typical OAD Dose Recommendations by Industry

• 0.5 to 3 4 tabs a day.
• To be increased with small increments, when
  needed.
• Recently France and Japan introduced
  glibenclamide tablet strength of 1.25 mg
  (suggesting that doses normally used were too
  large).

28
Glipizide slow-released (S-R)tablet

• Glipizide S-R tabl, 5 and 10 mg.
• Tablet may not be halved or chewed.
• Should be dispensed in original container.
• Try the 5 mg tablets first.
• Clinically, glipizide S-R mimics the
  multiple-small-dose principle, minimizing
  hypoglycemic bouts.

29
Dose comparison glipizide S-R vs normal tablet
30
Glipizide GITS vs Immediate-Release Glipizide
Steady-State Plasma Concentration
Steady-State ConcentrationsPlasma Glipizide
(ng/mL)
Glipizide GITS 20 mg single dose
Immediate-Release Glipizide 10 mg bid
Hours
N20 Male Patients with Type 2 Diabetes Data on
File (Pfizer)
31
Using Insulin

• Insulin should be used when OADs are not
  satisfactory in Diabetes type 2.
• Insulin causes great risk of hypoglycemia.
• To attain more even glucose control insulin can
  be combined with small doses of sulfonylureas
  and/or metformin.
• It gives the benefit of stimulation of the
  pancreas or improving insulin resistance.

32
Actrapid or Mixtard ?

• Depends on eating habits.
• One could adjust to habits rather than forcing up
  a change of eating habit.
• With 3 main meals and no snacks as habit,
  Actrapid TID might be preferred (?).
• When eating the whole day in smaller portions,
  Mixtard would be better.

33
Mixing Insulins ?

• Regular insulin use is well-known.
• Mixtard is a combination of long-acting
  (Monotard) and regular (Actrapid) insulin in
  7030 parts (in Indonesia).
• This is suitable to cover a days average insulin
  needs.
• There should be little need to make own
  combinations of Monotard with Actrapid, which in
  practice is dangerous mixing.

34
Combining Insulin with OAD

• Insulin can be combined with an OAD
• (small multiple dosing before meals), when OAD
  alone is not enough.
• Glipizide S-R provides a good alternative,
  because of once a day dose and smaller chance of
  hypoglycemia.
• Glipizide S-R may serve as a buffer treatment,
  while the insulin requirement is adjusted (daily)
  to need.

35
Using Multiple Drugs in Diabetes Control

• 1. OADs have different mechanisms of action.
• 2. Hypoglycemia may be dangerous.
• 3. Combining OADs produces an additive effect.
• 4. This strategy has been used in hypertension
  treatment with success.
• 5. Using different OADs with different mechanisms
  allows one to use smaller doses of each,
  minimizing hypoglycemic risk.

36
Change of Insulin or OAD requirement

• Watch for sudden changes (up or down) of insulin
  or OAD requirement, especially in frail subjects.
• Precipitated by diarrhea, loss of appetite,
  eating behavior, changes in electrolytes,
  hemodynamics, kidney function worsening, etc.
• May drop (suddenly, overnight) by 50, or
  increase.

37
FDA Chinese Herbals contain glibenclamide and
phenformin

• Diabetes Hypoglucose capsules.
• Pearl Hypoglycemic capsules.
• Tongyi Tang Diabetes Angel Hypoglycemic capsules.
• Zhen Qi capsules.
• Also Indonesian herbal drugs.

(WHO Pharmaceutical Newsletter, Nov 2, 2000)
38
Conclusion (1)

• Diabetes control is among the worst of successes
  of chronic disease management, and 84 (US data)
  has failed, risking complications.
• Theories of diabetic treatment should be
  accompanied by individualized practical patient
  approaches to be successful.
• Now, with new concepts, hyperglycemia can be well
  managed with less hypoglycemias and less
  long-term complications.

39
Conclusion (2)

• When hypoglycemic at about 1100 AM after single
  morning dose of potent OAD - such as
  glibenclamide - watch for hypo-hyper
  phenomenon.
• Use smaller divided doses of glibenclamide
  instead
• when 2 tabl. of glibenclamide is used, lower to
  3 X 1/2 tabl a day, or switch to glipizide S-R
  (single dose).
• Add another drug with different mechanism of
  action (metformin, repaglinide, acarbose, or
  glitazone) when HbA1c is gt7.
• Mixtard should be considered later for add-on,
  if oral drugs are not satisfactory.

40
E-mail ltpuko98_at_indosat.net.idgtHomepage
lthttp//www.iwandarmansjah.web.idgt

• Thank you !