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Aims of treatment
Conventional
HbA1c (%)
Intensive
7
6 0
9 6 Years of treatment
12
15
Beta-cell dysfunction
Insulin production
Henry 1998
Slides current until 2008
Mechanisms of action
Alpha-glucosidase inhibitors slow absorption of sucrose and starch Thiazolidinediones and biguanides reduce insulin resistance
Slides current until 2008
ACTIVITY
What are the most common oral blood glucose-lowering medicines in your community?
What are their brand names and generic names?
Two (or more) oral blood glucoselowering medicines that have different mechanisms of action Two medications rather than increase in initial medicine to maximum dosage Fewer side effects than monotherapy at higher doses
Slides current until 2008
1.0-1.5%
0.5%
Canadian Diabetes Association 2003
Slides current until 2008
Check that people understand how and when to take their medicines
Clarify the benefits of treatment Keep regimens simple Minimize costs Discuss adverse effects
Rubin 2005
Slides current until 2008
HbA1C
Target for people who can achieve it (without too much
hypoglycemia)1
Pre-meal
4-6 mmol/L
2 hours post-meal
5-8 mmol/L
< 6%
Target for most people with diabetes IDF Global guideline for Type 2 diabetes3
<7%
4-7mmol/L1 90-130mg/dl*2
<6.5%
<6.0mmol/L <110mg/dl
1CDA
IDF 2005
HbA1c
BMI
>25
Suggested medicine
Biguanide alone or in combination 1 or 2 agents from different classes 2 medicines from different classes or insulin
<9%
>9%
<25
CDA 2003
Increasing or adding
If goals have not been reached within 2-3 months, medication should be increased or medication from a different class added
Target levels should be reached within 6 months
Biguanides
Action not fully understood Decreases glucose production in liver Mild and variable effect on muscle sensitivity to insulin Side effects Gastrointestinal (nausea, abdominal discomfort or diarrhea and occasional constipation) Lactic acidosis
Slides current until 2008
Biguanides
Contraindications Renal insufficiency Liver failure Heart failure Severe gastrointestinal disease Advantages Do not cause hypoglycaemia when used as mono-therapy Do not cause weight gain; may contribute to weight loss
Slides current until 2008
Biguanides
First-line treatment in overweight or obese people Do not cause weight gain Have some effect on resistance at the periphery
Biguanides
Caution
Should be discontinued 24 hours before procedures requiring intravenous contrast dye Can be restarted 48 hours after the procedure if renal function is not compromised
Sulphonylureas
Increase insulin secretion regardless of blood glucose levels Many different medicines in this class Side effects Hypoglycaemia Stimulate appetite and provoke weight gain Nausea, fullness, heartburn Occasional rash Swelling
Slides current until 2008
Sulphonylureas
Short-acting secretagogues Meglitinides increase insulin secretion in response to increasing blood glucose levels (i.e. after eating)
Side effects Hypoglycaemia (probably less than sulphonylureas) Weight gain
Slides current until 2008
Sulphonylureas
Sulphonylureas
Things to remember
Some sulphonylureas have slower onset and lower peak than glyburide, thus may provoke less hypoglycaemia
Some need to be taken only once a day, therefore may be easier to remember to take First generation sulphonylureas, such as chlorpropamide may accumulate and cause hypoglycaemia due to their long duration of action
Slides current until 2008
Thiazolidinediones
Improve sensitivity to insulin in muscle, adipose tissue and liver Reduce glucose output from liver Changes fat distribution by decreasing visceral fat and increasing peripheral fat
Side effects Weight gain, fluid retention Upper respiratory infection and headache Decrease in haemoglobin
Slides current until 2008
Thiazolidinediones
Contraindications Liver disease, heart failure or history of heart disease Pregnancy and breast feeding
Slow digestion of sucrose and starch and therefore delay absorption Slow post-meal rise in blood glucose Side effects Flatulence, abdominal discomfort , diarrhoea As mono-therapy will not cause hypoglycaemia Hypoglycaemia when used with other medicine (e.g. a sulphonylurea)
Slides current until 2008
Contraindications Intestinal diseases, such as Crohns Autonomic neuropathy affecting the gastro-intestinal tract
Must be taken just before a meal
Slides current until 2008
Improves beta-cell responsiveness to increasing glucose levels Decreases glucagon secretion Slows gastric emptying Results in a feeling of fullness Must be injected subcutaneously twice a day, within 30-60 minutes before a meal Reduces HbA1c by ~1% Side effects Nausea Weight loss Diarrhoea Risk of hypoglycaemia when used with a sulphonylurea Slides current until 2008
Contraindications End-stage kidney disease or renal impairment Pregnancy Severe gastrointestinal disease
Beware of the possible reductions in General good health (with other concomitant conditions) Kidney function (and increased risk of hypoglycaemia) Family support and monitoring Vision Flexibility and activities of daily living Remember also Poly-pharmacy increases the risk of medicine-related adverse events To review all medication and complementary therapies Slides current until 2008
Always start with the lowest dose of any blood glucose-lowering medicine and increase gradually Using shorter-acting medicines reduces the risk of hypoglycaemia
Hypoglycaemia may increase the risk of falls and heart attack in older people
Slides current until 2008
Forgetfulness
Poor motivation Depression Cognitive deficits Poly-pharmacy Reduced manual dexterity These impact on the ability to maintain self-care and achieve maximum benefits from blood glucose-lowering medicines.
Slides current until 2008
ACTIVITY
Biguanide
Glitazones Meglitinides Alpha-glucosidase inhibitors Incretin mimetic agent
ACTIVITY
Case study
AB has had type 2 diabetes for two years
No medication
AB says he has no time for exercise and will not change his meal pattern What medication do you think should be started and why?
Summary
Review question
1. Which of the following adverse reactions are most likely due to metformin therapy?
a. Oedema b. Diarrhea c. Heart failure d. Weight gain
Review question
Review question
3. Which statement is FALSE?
a. All oral medicines used to treat diabetes should be discontinued once insulin is started b. In most people, blood glucose-lowering medicines become less effective over time c. Blood glucose-lowering medicines from different classes are often used in combination to reach target blood glucose d. It is important to be physically active and follow a prescribed meal plan in addition to blood glucose-lowering medicines
Slides current until 2008
Review question
JL is a 45-year-old man. He has been taking 5 mg glyburide and 500 mg metformin at breakfast and supper. His fasting blood glucose ranges from 5.36.7mmol/L but he has been experiencing hypoglycaemia most days at 3 or 4 pm. 4. What is the likely cause of JLs low blood sugars? a. Breakfast metformin b. Supper metformin c. Breakfast glyburide d. Supper glyburide
Slides current until 2008
Review question
5. When filling his prescription for a sulphonylurea, what is the most important thing to discuss with John?
a. What and when to eat b. When to take the medication c. How to recognize and treat hypoglycaemia d. When to see his doctor again
Answers
1. b
2. b 3. a 4. c 5. c
References
1.
2. 3. 4.
5.
6.
7. 8.
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in person with diabetes with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53. Ahmann AJ, Riddle MC. Current blood glucose lowering medicines for type 2 diabetes. Postgrad Med 2002; 111(5): 32-46. Henry RR. Type 2 diabetes care: the role of insulin-sensitizing agents and practical implications for cardiovascular disease prevention. Am J Med 1998; 105(1A): 20S-26S. Luna B, Feinglos MN. Blood glucose-lowering medicines in the management of type 2 diabetes mellitus. Am Fam Physician 2001; 63(9): 1747-56. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diab 2003; 27(supple 2). Yki-Jarvinnen H, Ryysy L, Nikkila K, et al. Comparison of bedtime insulin regimen in person with diabetes with type 2 diabetes mellitus; a randomized control trial. Annals Intern Med 1999; 130(5): 89-96. Amylin Pharmaceuticals Inc and Eli Lilly & Co. Byetta (cited 2005July 25) (16 screens). (Available from: http://www.byetta.com) Rubin Rr. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med 2005; 118(5A): 275-345.