Post on 25-Dec-2015
transcript
LONG TERM BENEFITS OF ORAL AGENTS
J. Robin Conway M.D.Diabetes ClinicSmiths Falls, ONwww.diabetesclinic.ca
Long Term Benefits of Oral Agents
Robin Conway M.D.
Physical Activity and Diabetes
• For people who have not previously exercised regularly and are at risk of CVD, an ECG stress test should be considered prior to starting an exercise program
Type Recommendation Example
Aerobic – especially type 2
150 minutes of moderate-intensity exercise each week
spread out over at least 3 non-consecutive days
gradually increase to 4 hours or more a week
sessions should be at least 10 minutes at a time
Brisk walking Biking Raking leaves Continuous swimming Dancing Water aerobics
Resistance – all persons with diabetes, including elderly
3 times a week start with 1 set of 10-15 repetitions progress to 2 sets of 10-15 then 3 sets of 8
Weight lifting Exercise with weight machines
Testing is particularly important before, during and for many hours after exercise.
Nutrition Therapy
People with diabetes should:
• Receive nutrition counseling by a registered dietitian
• Receive individualized meal planning
• Follow Canada’s Guidelines for Healthy Eating
• People on intensive insulin should also be taught to adjust the insulin for the amount of carbohydrate consumed
Pharmacologic Management of Type 2 Diabetes
• Add anti-hyperglycemic agents if:Diet & exercise therapy do not achieve targets
after 2-3 month trialor
newly diagnosed and has an A1C of 9%
Intensify to reach targets in 6-12 months
A1C
& BMI Suggested starting agent
< 9%
BMI 25
Biguanide alone or in combination
BMI < 25
1 or 2 agents from different classes
9%
--2 agents from different classes or insulin basal and/or preprandial
Clinical assessment and initiation of nutrition therapy and physical activity
Mild to moderate hyperglycemia (A1C<9.0%) Marked hyperglycemia (A1C 9.0%)
Basal and/or preprandial
insulin
Non-overweight Overweight 2 antihyperglycemic agents from different
classes1 or 2
antihyperglycemic agents from different
classes
Biguanide alone or in
combination
If not at targetIf not at target If not at target If not at target
Add a drug from a different class or use insulin alone or in combination
Add an oral antihyperglycemic agent from a different class or
insulin
Intensify insulin regimen or add
antihyperglycemic agents
Management of Hyperglycemia in Type 2 Diabetes Patients
Oral Agents for Type 2 Diabetes
SMBG is recommended at least once daily
• Combination at less than maximal doses result in more rapid improvement of blood glucose
• Counsel patients about hypoglycemia prevention and treatment
Class Expected decrease in A1C with monotherapy
Αlpha-glucosidase inhibitor 0.5 – 0.8
Biguanide 1.0 – 1.5
Insulin Depends on regimen
Insulin secretagogues 1.0 – 1.5 0.5 for nateglinide
Insulin sensitizers (TZDs) 1.0 – 1.5
Combined rosiglitazone and metformin 1.0 – 1.5
Antiobesity agent (orlistat) 0.5
Targets for Glycemic Control
* Treatment goals and strategies must be tailored to the patient, with consideration given to individual risk factors
A1C (%)
FPG/preprandial (mmol/L)
2h Postprandial (mmol/L)
Target for most patients 7.0 4.0 – 7.0 5.0 – 10.0
Normal range (if it can be safely achieved)
6.0 4.0 – 6.0 5.0 – 8.0
To achieve an A1C 7.0%, patients should aim for FPG, preprandial and postprandial PG targets
Burden of Poor Control - Cost
45004700490051005300550057005900610063006500
6 7 8 9 10
HbA1c
cost
/pat
ien
t/ye
ar
Diabetes only Diab, HT, Heart dis
Burden of Poor Control - Cost
Estimate annual cost to health plans by level of glycemic control
Determine effect of Improved Glycemic Control on Health Care Utilization and Costs
4500
9500
14500
19500
24500
6 7 8 9 10
HbA1c
cost
/pat
ien
t/ye
ar
Diabetes only Diab, HT, Heart dis
Meltzer et al CMAJ 1998;159(Suppl):S1-29.
Oral Antihyperglycemic Agents: Biguanides
• Decreases hepatic glucoseproduction, enhances peripheral glucose uptake
– May reduce insulin resistance in the periphery
– e.g., Metformin
– Contraindicated in renal/hepatic insufficiency
– May cause GI side effects
– Not associated with hypoglycemia, may promote weight loss
MUSCLELIVER
Plosker, Faulds Drugs 1999;57:410-32. Balfour, Plosker Drugs 1999;57:921-30.
MUSCLE
ADIPOSE TISSUE
LIVER
Oral Antihyperglycemic Agents: Thiazolidinediones (TZDs)
• Decrease insulinresistance– Increase insulin-dependent
glucose disposal, decrease hepatic glucose production– e.g., Pioglitazone, rosiglitazone– Pioglitazone has a positive effect on lipids– Not associated with hypoglycemia– Possible URI, headache, edema, weight gain and
reduction in hemoglobin
TZD
INSULIN
RECEPTOR
RNADNA
Saltiel, Olefsky Diabetes 1996;45:1661–9.
Thiazolidinediones: Mechanism of Insulin Sensitization
TZD
PPAR
INSULIN
GLUT-4
GLUCOSE
Durability of Glycemic Control with Pioglitazone Long Term
7.5
8
8.5
9
9.5
10
10.5
baseline endpoint week 12 week 24 week 36 week 48 week 60 week 72
rollover placebo
rollover pioglitazone
Einhorn D et al. Diabetes 2001;50 (suppl2):A111
Hb
A1c
(%
)
Metformin & Pioglitazone Study - Open Label Extension
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
end of DB STUDY week 24 week 48 week 72
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Hb1c
fasting glucose
Change in HbA1c (%) Change in fasting glucose (mmol/L)
Einhorn et al. Clin Therapeutics 2000;12:1395-1409
Oral Antihyperglycemic Agents: Sulfonylureas
• Stimulate pancreatic insulin release
– e.g., First-generation: tolbutamide, chlorpropamide, acetohexamide
– e.g., Second-generation: Glyburide, gliclazide
– Secondary failure a problem– Weight gain, risk of hypoglycemia
Meltzer et al CMAJ 1998;159(Suppl):S1-29.
PANCREAS
Natural History of Type 2 Diabetes
Normal Impaired glucosetolerance
Type 2 diabetes
Time
Insulinresistance
Insulinproduction
Glucoselevel
-celldysfunction
Henry. Am J Med 1998;105(1A):20S-6S.
Oral Antihyperglycemic Agents: Alpha-glucosidase inhibitors
• Slows gut absorptionof starch and sucrose
– Attenuates postprandial increases in blood glucose levels
– e.g., Acarbose – GI side effects– Not associated with hypoglycemia or weight
gain
Salvatore, Giugliano Clin Pharmacokinet 1996;30:94-106.
INTESTINE
Oral Agents for Type 2 Diabetes
SMBG is recommended at least once daily
• Combination at less than maximal doses result in more rapid improvement of blood glucose
• Counsel patients about hypoglycemia prevention and treatment
Class Expected decrease in A1C with monotherapy
Αlpha-glucosidase inhibitor 0.5 – 0.8
Biguanide 1.0 – 1.5
Insulin Depends on regimen
Insulin secretagogues 1.0 – 1.5 0.5 for nateglinide
Insulin sensitizers (TZDs) 1.0 – 1.5
Combined rosiglitazone and metformin 1.0 – 1.5
Antiobesity agent (orlistat) 0.5
Natural History of Type 2 Diabetes
Normal Impaired glucosetolerance
Type 2 diabetes
Time
Insulinresistance
Insulinproduction
Glucoselevel
-celldysfunction
Henry. Am J Med 1998;105(1A):20S-6S.
LifestyleLifestyle
Metformin/ThiazolidinedionesMetformin/Thiazolidinediones
SecretagoguesSecretagoguesInsulinInsulin
Targets for Glycemic Control
* Treatment goals and strategies must be tailored to the patient, with consideration given to individual risk factors
A1C (%)
FPG/preprandial (mmol/L)
2h Postprandial (mmol/L)
Target for most patients 7.0 4.0 – 7.0 5.0 – 10.0
Normal range (if it can be safely achieved)
6.0 4.0 – 6.0 5.0 – 8.0
To achieve an A1C 7.0%, patients should aim for FPG, preprandial and postprandial PG targets