pharmacological management blood glucose-lowering medicines
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Pharmacological management Blood glucose-lowering medicines. Aims of treatment. Reduce the symptoms of hyperglycaemia Limit adverse effects of treatment Maintain quality of life and psychological well-being Prevent or delay vascular complications of diabetes. 0. 3. 6. 9. 12. 15. - PowerPoint PPT PresentationTRANSCRIPT
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Pharmacological managementBlood glucose-lowering medicines
Blood glucose-lowering medicinesCurriculum Module III-2
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Aims of treatment
• Reduce the symptoms of hyperglycaemia
• Limit adverse effects of treatment• Maintain quality of life and
psychological well-being• Prevent or delay vascular
complications of diabetes
Blood glucose-lowering medicinesCurriculum Module III-2
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UKPDS: long-term glucose control
06
7
8
9
0 3 6 9 12 15
HbA 1
c (%
)
Years of treatment
Conventional
Intensive
UKPDS Study Group 1998
Blood glucose-lowering medicinesCurriculum Module III-2
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Natural history of type 2 diabetes
Normal Impaired glucosetolerance
Type 2 diabetesTime
Insulin resistance
Insulinproduction
Glucoselevel
Beta-celldysfunction
Henry 1998
Blood glucose-lowering medicinesCurriculum Module III-2
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Mechanisms of action
Insulin secretagogues: sulphonylureas and meglitinides increase insulin production
Biguanides and thiazolidinedionesreduce glucose production
Thiazolidinediones and biguanides reduce insulin resistance
Alpha-glucosidase inhibitors slow absorption of sucrose and starch
GLP-1 (incretins) improve response to glucose level
Blood glucose-lowering medicinesCurriculum Module III-2
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Understanding the names
• Chemical name relates to chemical structure
• Generic name identifies a unique compound with therapeutic properties
• Brand name given by the manufacturer
Blood glucose-lowering medicinesCurriculum Module IV-1
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• What are the most common oral blood glucose-lowering medicines in your community?
• What are their brand names and generic names?
Blood glucose-lowering medicinesCurriculum Module III-2
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The principles of combination therapy
• Two (or more) oral blood glucose-lowering medicines that have different mechanisms of action
• Two medications rather than increase in initial medicine to maximum dosage
• Fewer side effects than mono-therapy at higher doses
Blood glucose-lowering medicinesCurriculum Module III-2
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Expected effect of blood glucose-lowering medicines
Class of medicine Expected decrease in HbA1C in mono-therapy
Alpha-glucosidase inhibitor
0.5-0.8%
Biguanide Insulin sensitisersMost insulin secretagoguesNateglinide
1.0-1.5%1.0-1.5%1.0-1.5%
0.5%Canadian Diabetes Association 2003
Blood glucose-lowering medicinesCurriculum Module III-2
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Strategies to help people remember
• 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
Blood glucose-lowering medicinesCurriculum Module III-2
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HbA1C Pre-meal 2 hours post-meal
Target for people who can achieve it (without too much hypoglycemia)1
< 6% 4-6 mmol/L 5-8 mmol/L
Target for most people with diabetes
<7% 4-7mmol/L1
90-130mg/dl*2
5-10mmol/L1
<180mg/dl2IDF Global guideline for Type 2 diabetes3
<6.5% <6.0mmol/L
<110mg/dl
<8.0mmol/L
<145mg/dl
Targets for blood glucose
1CDA 2003, 2ADA 2004, 3 IDF 2005
Blood glucose-lowering medicinesCurriculum Module III-2
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Suggested starting medicine
HbA1c BMI Suggested medicine
<9%
>25 Biguanide – alone or in combination
<25 1 or 2 agents from different classes
>9% 2 medicines from different classes or insulin
CDA 2003
Blood glucose-lowering medicinesCurriculum Module III-2
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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
• Insulin should be added if necessary to reach target levels
Blood glucose-lowering medicinesCurriculum Module III-2
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Biguanides
• Action not fully understood• Decreases glucose production in liver• Mild and variable effect on muscle
sensitivity to insulinSide effects• Gastrointestinal (nausea, abdominal
discomfort or diarrhea and occasional constipation)
• Lactic acidosis
Blood glucose-lowering medicinesCurriculum Module III-2
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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
Blood glucose-lowering medicinesCurriculum Module III-2
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Biguanides
First-line treatment in overweight or obese people• Do not cause weight gain• Have some effect on
resistance at the periphery
Blood glucose-lowering medicinesCurriculum Module III-2
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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
Blood glucose-lowering medicinesCurriculum Module III-2
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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
Blood glucose-lowering medicinesCurriculum Module III-2
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Sulphonylureas
Short-acting secretagoguesMeglitinides – increase insulin secretion in response to increasing blood glucose levels (i.e. after eating)Side effects• Hypoglycaemia (probably less than sulphonylureas)• Weight gain
Blood glucose-lowering medicinesCurriculum Module III-2
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Sulphonylureas
Contraindications• Type 1 diabetes• Pregnancy• Breastfeeding
Sulphonylureas - Use cautiously with liver or kidney diseaseMeglitinides - Severe impairment of liver function
Blood glucose-lowering medicinesCurriculum Module III-2
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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
Blood glucose-lowering medicinesCurriculum Module III-2
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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
Blood glucose-lowering medicinesCurriculum Module III-2
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Thiazolidinediones
Contraindications• Liver disease, heart failure or history
of heart disease• Pregnancy and breast feeding
They are not contraindicated in renal insufficiencyPotential benefits• Reduced levels of LDL-cholesterol and
increased level of HDL-cholesterol
Blood glucose-lowering medicinesCurriculum Module III-2
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Alpha glucosidase inhibitors
• Slow digestion of sucrose and starch and therefore delay absorption
• Slow post-meal rise in blood glucoseSide effects• Flatulence, abdominal discomfort ,
diarrhoea• As mono-therapy will not cause
hypoglycaemia• Hypoglycaemia when used with other
medicine (e.g. a sulphonylurea)
Blood glucose-lowering medicinesCurriculum Module III-2
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Alpha glucosidase inhibitors
Contraindications• Intestinal diseases, such as
Crohn’s• Autonomic neuropathy
affecting the gastro-intestinal tract
Must be taken just before a meal
Blood glucose-lowering medicinesCurriculum Module III-2
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GLP-1 (incretin mimetic agent)
• 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
Blood glucose-lowering medicinesCurriculum Module III-2
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GLP-1 (incretin mimetic agent)
Contraindications• End-stage kidney disease or
renal impairment• Pregnancy• Severe gastrointestinal disease
Blood glucose-lowering medicinesCurriculum Module III-2
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DPP-4 InhibitorsA new class of medications called DPP-4 inhibitors help improve A1C without causing hypoglycemia.
They work by by preventing the breakdown of a naturally occuring compound in the body, GLP-1.
GLP-1 reduces blood glucose levels in the body, but is broken down very quickly so it does not work well when injected as a drug itself. By interfering in the process that breaks down GLP-1, DPP-4 inhibitors allow it to remain active in the body longer, lowering blood glucose levels only when they are elevated.
DPP-4 inhibitors do not tend to cause weight gain and tend to have a neutral or positive effect on cholesterol levels. Sitagliptin(Januvia), saxagliptin(Onglyza) and Vidagliptin(Galvus) are currently DPP-4 inhibitors on the market .
ADA
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Blood glucose-lowering medicinesCurriculum Module III-2
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Older people with diabetes
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
Blood glucose-lowering medicinesCurriculum Module III-2
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Older people with diabetes
• 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
Blood glucose-lowering medicinesCurriculum Module III-2
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Older people with diabetes
Remember the possibility of• Forgetfulness• Poor motivation• Depression• Cognitive deficits• Poly-pharmacy• Reduced manual dexterityThese impact on the ability to maintain self-care and achieve maximum benefits from blood glucose-lowering medicines.
Blood glucose-lowering medicinesCurriculum Module III-2
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Ineffectiveness of blood glucose-lowering medicines
If oral blood glucose-lowering medicines are ineffective• Check diet and exercise• Consider adding intermediate or long-acting insulin at bedtime• Maintain metformin• Consider reducing or stopping the morning sulphonylurea
Blood glucose-lowering medicinesCurriculum Module IV-1
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Class of medicine Likely to cause weight gain
Likely to cause hypoglycaemia
Target post-meal glucose
Sulphonylureas
Biguanide
Glitazones
Meglitinides
Alpha-glucosidase inhibitorsIncretin mimetic agent & DPP Inhibitors
Blood glucose-lowering medicinesCurriculum Module IV-1
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Case study
• AB has had type 2 diabetes for two years• 51-year-old truck driver• BMI of 32, blood pressure at 150/95• HbA1C 9.5%• No medication• AB says he has no time for exercise and will
not change his meal patternWhat medication do you think should be started
and why?
Blood glucose-lowering medicinesCurriculum Module III-2
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Summary
• Lifestyle changes first
• Start medicine as soon as needed
• Add a different kind
• No delay starting insulin
Blood glucose-lowering medicinesCurriculum Module III-2
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Review question
1. Which of the following adverse reactions are most likely due to metformin therapy?
a. Oedemab. Diarrheac. Heart failured. Weight gain
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Review question
2. Which of the following statements best describes alpha-glucosidase inhibitors?
a. Likely to cause weight gainb. Should be taken with first bite of
the mealc. Commonly associated with
hypoglycaemiad. Well tolerated, few side effects
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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
Blood glucose-lowering medicinesCurriculum Module III-2
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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 5.3–6.7mmol/L but he has been experiencing hypoglycaemia most days at 3 or 4 pm. 4. What is the likely cause of JL’s low blood sugars?
a. Breakfast metformin b. Supper metforminc. Breakfast glyburided. Supper glyburide
Blood glucose-lowering medicinesCurriculum Module III-2
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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 medicationc. How to recognize and treat
hypoglycaemiad. When to see his doctor again
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Answers
1. b
2. b
3. a
4. c
5. c
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References
1. 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.
2. Ahmann AJ, Riddle MC. Current blood glucose lowering medicines for type 2 diabetes. Postgrad Med 2002; 111(5): 32-46.
3. 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.
4. Luna B, Feinglos MN. Blood glucose-lowering medicines in the management of type 2 diabetes mellitus. Am Fam Physician 2001; 63(9): 1747-56.
5. 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).
6. 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.
7. Amylin Pharmaceuticals Inc and Eli Lilly & Co. Byetta (cited 2005July 25) (16 screens). (Available from: http://www.byetta.com)
8. Rubin Rr. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med 2005; 118(5A): 275-345.