slides current until 2008 pharmacological management blood glucose-lowering medicines

Slides current until 2008

Pharmacological managementBlood glucose-lowering medicines

Blood glucose-lowering medicinesCurriculum Module III-2

Slide 2 of 41


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


Slide 3 of 41


UKPDS: long-term glucose control

06

7

8

9

0 3 6 9 12 15

Hb

A1

c (%

)

Years of treatment

Conventional

Intensive

UKPDS Study Group 1998


Slide 4 of 41


Natural history of type 2 diabetes

Normal Impaired glucosetolerance

Type 2 diabetes

Time

Insulin resistance

Insulinproduction

Glucoselevel

Beta-celldysfunction

Henry 1998


Slide 5 of 41


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


Slide 6 of 41


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

Slide 7 of 41ACTIVITY


• What are the most common oral blood glucose-lowering medicines in your community?

• What are their brand names and generic names?


Slide 8 of 41


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


Slide 9 of 41


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 sensitisers

Most insulin secretagogues

Nateglinide

1.0-1.5%

1.0-1.5%

1.0-1.5%

0.5%Canadian Diabetes Association 2003


Slide 10 of 41


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


Slide 11 of 41


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/dl2

IDF 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


Slide 12 of 41


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


Slide 13 of 41


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


Slide 14 of 41


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


Slide 15 of 41


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


Slide 16 of 41


Biguanides

First-line treatment in overweight or obese people

• Do not cause weight gain

• Have some effect on resistance at the periphery


Slide 17 of 41


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


Slide 18 of 41


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


Slide 19 of 41


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


Slide 20 of 41


Sulphonylureas

Contraindications• Type 1 diabetes• Pregnancy• Breastfeeding

Sulphonylureas - Use cautiously with liver or kidney diseaseMeglitinides - Severe impairment of liver function


Slide 21 of 41


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


Slide 22 of 41


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


Slide 23 of 41


Thiazolidinediones

Contraindications• Liver disease, heart failure or history

of heart disease• Pregnancy and breast feeding

They are not contraindicated in renal insufficiency

Potential benefits• Reduced levels of LDL-cholesterol and

increased level of HDL-cholesterol


Slide 24 of 41


Alpha glucosidase inhibitors

• 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)


Slide 25 of 41


Alpha glucosidase inhibitors

Contraindications• Intestinal diseases, such as

Crohn’s• Autonomic neuropathy

affecting the gastro-intestinal tract

Must be taken just before a meal


Slide 26 of 41


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


Slide 27 of 41


GLP-1 (incretin mimetic agent)

Contraindications• End-stage kidney disease or

renal impairment• Pregnancy• Severe gastrointestinal disease


Slide 28 of 41

DPP-4 Inhibitors

A 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



Slide 29 of 41


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


Slide 30 of 41



• 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


Slide 31 of 41



Remember the possibility of

• 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.


Slide 32 of 41


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




Class of medicine Likely to cause weight gain

Likely to cause hypoglycaemia

Target post-meal glucose

Sulphonylureas

Biguanide

Glitazones

Meglitinides

Alpha-glucosidase inhibitors

Incretin mimetic agent & DPP Inhibitors




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 pattern

What medication do you think should be started and why?


Slide 35 of 41


Summary

• Lifestyle changes first

• Start medicine as soon as needed

• Add a different kind

• No delay starting insulin


Slide 36 of 41


Review question

1. Which of the following adverse reactions are most likely due to metformin therapy?

a. Oedemab. Diarrheac. Heart failured. Weight gain


Slide 37 of 41


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


Slide 38 of 41


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


Slide 39 of 41


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 metformin

c. Breakfast glyburide

d. Supper glyburide


Slide 40 of 41


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


Slide 41 of 41


Answers

1. b

2. b

3. a

4. c

5. c


Slide 42 of 41


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.

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