Type 2 Diabetes: How sweet it is!
Dr. Jeremy Gilbert
Division of Endocrinology
Assistant Professor
University of Toronto
Faculty/Presenter Disclosure
• Faculty: Dr. Jeremy Gilbert
• Program: 51st Annual Scientific Assembly
• Relationships with commercial interests:
– Honoraria:
– AstraZeneca
– Bristol Meyers Squibb
– Eli Lilly
– Merck
– Novonordisk
– Sanofi
Disclosure of Commercial
Support
• This program has received financial support n/a from in the form of n/a
• This program has received in-kind support from n/a in the form of n/a
• Potential for conflict(s) of interest:
– Dr. Jeremy GIlbert has received no payment from any organization supporting
this program AND/OR organization whose product(s) are being discussed in
this program.
Mitigating Potential Bias
• All recommendations will be based on the Canadian Diabetes
Association Guidelines and relevant medical literature.
OBJECTIVES
• 1. Review highlights from the 2013 Canadian
Diabetes Association Guidelines including
diagnostic criteria and treatment goals
• 2. Discuss anti-hyperglyemic agent options
after Metformin, focussing on newer
medication options
• 3. Explore the complications of Diabetes and
examine vascular protective strategies in
individuals with Diabetes
www.guidelines.diabetes.ca
How common is Diabetes?
Diabetes in Canada: Prevalence by
Province and Territory
Age-standardized† prevalence of diagnosed DM among individuals ≥ 1 year, 2008/09
YT
5.4%
BC
5.4%
< 5.0
5.0 < 5.5
5.5 < 6.0
6.0 < 6.5
≥ 6.5
NT
5.5%
NU
4.4%
AB
4.9%
NL
6.5%
MB
5.9%
SK
5.4%
† Age-standardized to the 1991 Canadian population.
ON
6.0%
QC
5.1%
PE
5.6%
NB
5.9%
NS
6.1%
NL, NS and ON had the highest prevalence, while
NU, AB and QC had the lowest.
Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011.
Diabetes in Canada: Prevalence of Diagnosed
Diabetes by age and sex
Prevalence of diagnosed diabetes among individuals aged ≥ 1 year, by age group
and sex, 2008/09
Overall Prevalence
30
Females
6.4%
Males
7.2%
Total
6.8%
Prevalence (%)
25
20
15
10
5
0
Age group (years) 1-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 ≥85 Canada
Prevalence increased with age. The sharpest increase occurred after age 40 years.
The highest prevalence was in the 75-79 year age group.
Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011.
Patients with DM are more likely to be
hospitalized for many conditions
Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).
The pathophysiology of T2DM includes
three main defects
Islet
α-cell produces excess
glucagon
Pancreas
β-cell produces
less insulin
1. Insulin deficiency
Excess
glucagon
Diminished
insulin
Hyperglycemia
Diminished
insulin
Muscle and fat
Liver
2. Excess glucose output
3. Insulin resistance
Type 2 Diabetes is a Progressive Disease
Beta Cell Function (%)
100
Stages of Type 2 diabetes in
relationship to ß-cell function
75
50
25
Impaired
glucose
tolerance
-12
-10
Postprandial
hyperglycemia
-6
Type 2
diabetes
phase I
-2
0
Type 2
diabetes
phase II
2
Type 2 diabetes
phase III
6
10
14
Years from Diagnosis
•
•
•
50% of ß-cell function is already lost at diagnosis
ß-cell function will continue to decline despite treatment
Majority of patients will eventually require insulin therapy
Lebovitz HE. Diabetes Review 1999; 7(3):139-53.
UKPDS Group. Diabetes 1995; 44:1249.
Progressive impairment in β-cell function
Diet/conv Rx (n=376)
Metformin (n=159)
SU/intensive (n=511)
β-cell function
declines, while . . .
10
9
75
HbA1c
β-cell function (%)
100
. . . hyperglycemia
increases
50
8
7
25
6
5
0
0
1
SU = sulfonylurea
2
3
Years
4
5
6
0
1
2
3
Years
4
5
6
UK Prospective Diabetes Study Group. Diabetes.
1995;44:1249–1258.
Question
• How often should should a FPG be done in
most individuals > 40 years of age:
A) every year
B) every 2 years
C) every 3 years
D) every 4 years
E) every 5 years
2013
Diagnosis of Diabetes
FPG ≥7.0 mmol/L
Fasting = no caloric intake for at least 8 hours
or
A1C ≥6.5% (in adults)
Using a standardized, validated assay, in the absence of factors that affect the
accuracy of the A1C and not for suspected type 1 diabetes
or
2hPG in a 75-g OGTT ≥11.1 mmol/L
or
Random PG ≥11.1 mmol/L
Random= any time of the day, without regard to the interval since the last meal
2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose
2013
Diagnosis of Prediabetes*
Test
Result
Prediabetes Category
Fasting Plasma
Glucose
(mmol/L)
6.1 - 6.9
Impaired fasting glucose
(IFG)
7.8 – 11.0
Impaired glucose tolerance
(IGT)
6.0 - 6.4
Prediabetes
2-hr Plasma Glucose in
a 75-g Oral Glucose
Tolerance Test (mmol/L)
Glycated
Hemoglobin
(A1C) (%)
* Prediabetes = IFG, IGT or A1C 6.0 - 6.4%  high risk of developing T2DM
Screening Checklist
 ASSESS all adults clinically every year for risk
of type 2 diabetes (T2DM)
 SCREEN every 3 years if ≥ 40 years or high risk
on risk calculator
 SCREEN earlier and more frequently if very
high risk on risk calculator or additional risk
factors present
 USE fasting plasma glucose (FPG) and/or A1C
as initial screening tests
Glycated Hemoglobin (A1C) /Glucose
A1C (%)
mmol/L
12% ________________ 16.5
11% __________________14.9
10% _________________ 13.4
9% __________________11.8
8% __________________10.1
7% ___________________ 8.6
6% ___________________ 7.0
Kollman (2008) Diabetes Care. 31:381-385
What is new in making the diagnosis
of diabetes?
2013
Individualizing A1C Targets
Consider 7.1-8.5% if:
which must be
balanced against
the risk of
hypoglycemia
Macro and Microvascular Benefits?
DCCT
n=1441 T1DM
Intensive
(≥ 3
injections/day
or CSII)
vs Conventional
(1-2 injections
per day)
Reduction in Retinopathy
Primary Prevention
Secondary Intervention
76% RRR
54% RRR
(95% CI 62-85%)
(95% CI 39-66%)
RRR = relative risk reduction CI = confidence interval
The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.
DCCT: Reduction in Albuminuria
Primary Prevention
Secondary Intervention
34% RRR
43% RRR
(p<0.04)
(p=0.001)
56% RRR
(p=0.01)
RRR = relative risk
Solid line = risk of developing microalbuminuria
Dashed line = risk of developing macroalbuminuria reduction
CI = confidence interval
The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
Reduction in Neuropathy
The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.
UKPDS: N = 3867 T2DM
9
Conventional
7.9%
A1C (%)
8
Intensive
7.0%
7
6
0 0
3
UKPDS Study Group. Lancet 1998:352:837-53.
6
9
12
15
Legacy Effect of Earlier Glucose
Control
After median 8.5 years post-trial follow-up
Aggregate Endpoint
1997
2007
Any diabetes related endpoint
RRR:
P:
12%
0.029
9%
0.040
Microvascular disease
RRR:
P:
25%
0.0099
24%
0.001
Myocardial infarction
RRR:
P:
16%
0.052
15%
0.014
All-cause mortality
RRR:
P:
6%
0.44
13%
0.007
Holman R, et al. N Engl J Med 2008;359.
Lifestyle Modification
&
Medications for hyperglycemia
How do we choose?
Macronutrient Distribution (% Total
Energy)
% of total
energy
Calories per
gram
Grams for 2000
calorie/day diet
BW = body weight
Carbohydrates
Protein
Fat
45-60%
15-20%
20-35%
(or 1-1.5g / kg BW)
4
4
9
225-300
75-100
44-78
2013
Physical Activity Checklist
 DO a minimum of 150 minutes of moderate-to
vigorous-intensity aerobic exercise per week
 INCLUDE resistance exercise ≥ 2 times a week
 SET physical activity goals and INVOLVE a multidisciplinary team
 ASSESS patient’s health before prescribing an
exercise regimen
Modest weight loss CAN make a
difference
• Goal is to prevent weight gain, promote weight loss
and prevent weight re-gain
• Weight loss of only 5-10% improves:
–
–
–
–
Insulin sensitivity
Glycemic control
Blood pressure
Lipid levels
It can be done!
460 Pounds
256 Pounds
2013
Pharmacotherapy in T2DM
checklist
 CHOOSE initial therapy based on degree of
hyperglycemia
 START with Metformin +/- others
 INDIVIDUALIZE your therapy choice based on
characteristics of the patient and the agent
 REACH TARGET within 3-6 months of diagnosis
AT DIAGNOSIS OF TYPE 2 DIABETES
Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin
L
I
F
E
S
T
Y
L
E
A1C <8.5%
If not at glycemic
target (2-3 mos)
Start / Increase
metformin
A1C 8.5%
Symptomatic hyperglycemia with
metabolic decompensation
Start metformin immediately
Consider initial combination with
another antihyperglycemic agent
Initiate
insulin +/metformin
If not at glycemic targets
Add an agent best suited to the individual:
Patient Characteristics
Degree of hyperglycemia
Risk of hypoglycemia
Overweight or obesity
Comorbidities (renal, cardiac, hepatic)
Preferences & access to treatment
Other
Agent Characteristics
BG lowering efficacy and durability
Risk of inducing hypoglycemia
Effect on weight
Contraindications & side-effects
Cost and coverage
Other
2013
See next page…
2013
GLP-1 Actions
Brain: reduced appetite
Food
intake
Stomach: reduced emptying
Beta-cells
Insulin release
Stomach
Pancreas
Blood glucose
DPP-4
GI tract
Net effect:
GLP-1
Glucagon secretion
α-cells
Intestine
Adapted from: Barnett A. Int J Clin Pract 2006;60:1454-70; Drucker DJ, et al. Lancet 2006;368:1696-705;
Idris I, et al. Diabetes Obes Metab 2007;9:153-65.
Impaired GLP-1 secretion in T2DM
Normal subjects
IGT
T2DM patients
20
GLP-1 (pmol/l)
* * * *
*
*
15
*
10
5
Baseline
0
0
*p<0.05
60
120
180
240
Time (min)
GLP-1 AUC T2DM vs. NGT is decreased by Toft-Nielsen MB, et al. J Clin Endocrinol Metab.
53%, p<0.001
2001;86:3717–3723.
Currently Available Incretins in Canada
• GLP-1 Analogues
– Liraglutide = Victoza
– Exenetide = Byetta
• More effective than DPPIV Inhibitors
• Potential weight loss
• Temporary Nausea
• Injections
• Expensive
• Long term safety data
• DPP-IV Inhbitors
– Sitaglipitin = Januvia
– Saxagliptin = Onglyza
– Linagliptin = Trajenta
• Less effective than GLP-1
Analogues
• Weight neutral
• Well tolerated
• Oral
• Often covered by ODB
• Long term safety data
Antihyperglycemic agents and Renal Function
CKD Stage:
GFR (mL/min):
5
< 15
4
15-29
3
30-59
30
Metformin
Linagliptin
15
Saxagliptin
15
Sitagliptin
25 mg
Exenatide
2.5 mg
≥ 90
60
50
30 50 mg
50
30
50
50
Liraglutide
Glyburide
1
25
Acarbose
Gliclazide/Glimepiride
2
60-89
15
30
30
50
Repaglinide
Thiazolidinediones
30
Not recommended / contraindicated
Caution and/or dose reduction
Safe
Adapted from: Product Monographs as of March 1, 2013; CDA Guidelines 2008; and Yale JF. J Am Soc Nephrol 2005; 16:S7-S10.
What are the
options for Insulin?
Types of Insulin
Insulin Type (trade name)
Onset
Peak
Duration
10 - 15 min
10 - 15 min
10 - 15 min
1 - 1.5 h
1 - 1.5 h
1-2h
3-5h
3-5h
3.5 - 4.75 h
30 min
2-3h
6.5 h
1-3h
5-8h
Up to 18 h
90 min
Not
applicable
Up to 24 h
(glargine 24 h,
detemir 16 - 24 h)
Bolus (prandial) Insulins
Rapid-acting insulin analogues (clear):
• Insulin aspart (NovoRapid®)
• Insulin glulisine (Apidra™)
• Insulin lispro (Humalog®)
Short-acting insulins (clear):
• Insulin regular (Humulin®-R)
• Insulin regular (Novolin®geToronto)
Basal Insulins
Intermediate-acting insulins (cloudy):
• Insulin NPH (Humulin®-N)
• Insulin NPH (Novolin®ge NPH)
Long-acting basal insulin analogues
(clear)
• Insulin detemir (Levemir®)
• Insulin glargine (Lantus®)
Types of Insulin (continued)
Insulin Type (trade name)
Time action profile
Premixed Insulins
Premixed regular insulin – NPH (cloudy):
• 30% insulin regular/ 70% insulin NPH
(Humulin® 30/70)
• 30% insulin regular/ 70% insulin NPH
(Novolin®ge 30/70)
• 40% insulin regular/ 60% insulin NPH
(Novolin®ge 40/60)
• 50% insulin regular/ 50% insulin NPH
(Novolin®ge 50/50)
Premixed insulin analogues (cloudy):
• 30% Insulin aspart/70% insulin aspart protamine
crystals (NovoMix® 30)
• 25% insulin lispro / 75% insulin lispro protamine
(Humalog® Mix25®)
• 50% insulin lispro / 50% insulin lispro protamine
(Humalog® Mix50®)
A single vial or cartridge contains a
fixed ratio of insulin
(% of rapid-acting or short-acting
insulin to % of intermediate-acting
insulin)
Serum Insulin Level
Time
Human Basal: Humulin-N, Novolin ge NPH
Analogue Basal: Lantus, Levemir
Human Bolus: Humulin-R, Novolin ge Toronto
Analogue Bolus: Apidra, Humalog, NovoRapid
Serum Insulin Level
Time
Human Premixed: Humulin 30/70, Novolin ge 30/70
Analogue Premixed: Humalog Mix25, NovoMix 30
What about Hypoglycemia?
3 phases of hypo treatment
1. Acute
2. Intermediate
3. Future
Acute
¾ cup OJ
6 LifeSavers
3 gluc tab
3 packs sugar
1 tbsp honey
Intermediate
15 min
recheck
Future
Why did it happen?
How do I prevent it?
Causes of hypo
Too little food
Too much activity
Too much insulin
Steps to Address Hypoglycemia
1. Recognize autonomic or neuroglycopenic symptoms
2. Confirm if possible (blood glucose <4.0 mmol/L)
3. Treat with “fast sugar” (simple carbohydrate) (15 g) to
relieve symptoms
4. Retest in 15 minutes to ensure the BG >4.0 mmol/L and
retreat (see above) if needed
5. Eat usual snack or meal due at that time of day or a
snack with 15 g carbohydrate plus protein
Hypoglycemia and Driving
Safe blood glucose (BG) prior to driving
BG ≥ 5.0 mmol/L
• If BG <5.0 mmol/L prior to driving:
– Take 15 g carbohydrate
– Re-check in 15 minutes
– When BG >5 mmol/L for at least 45 minutes  safe to
drive
• Need to re-check BG every 4 hours of continuous
driving and carry simple carbohydrate snacks
Iain S. Begg et al . Canadian Journal of Diabetes. 2003;27(2):128-140.
Diabetes Complications
Macrovascular
Cerebral vascular disease
2-4 fold increase in CV
mortality & stroke
Microvascular
Retinopathy
Leading cause of blindness in
working-age adults
Coronary artery disease
8/10 will die from a CV event
Nephropathy
Leading cause of ESRD
Erectile Dysfunction
Peripheral
vascular disease
Peripheral Neuropathy
Leading cause of non-traumatic
LEA
Foot problems
C J Diabetes (2008); 32(suppl1): S1-S201
Who Should Receive Statins?
2013
•
•
•
•
≥40 yrs old or
Macrovascular disease or
Microvascular disease or
DM >15 yrs duration and age >30 years
or
• Warrants therapy based on the 2012
Canadian Cardiovascular Society lipid
guidelines
Among women with childbearing potential, statins should only
be used in the presence of proper preconception counseling &
reliable contraception. Stop statins prior to conception.
Who Should Receive ACEi or ARB
Therapy?
2013
• ≥55 years of age or
• Macrovascular disease or
• Microvascular disease
At doses that have shown vascular protection (ramipril 10 mg daily,
perindopril 8 mg daily, telmisartan 80 mg daily)
Among women with childbearing potential, ACEi or ARB should
only be used in the presence of proper preconception
counseling & reliable contraception. Stop ACEi or ARB either
prior to conception or immediately upon detection of pregnancy
Summary of Pharmacotherapy for Hypertension
in Patients with Diabetes
Threshold equal or over 130/80 mmHg and Target below 130/80 mmHg
With
Nephropathy,
CVD or CV
risk factors
ACE Inhibitor
or ARB
Diabetes
Without
the above
1. ACE Inhibitor
or ARB or
2. Thiazide diuretic
or DHP-CCB
Combination of 2 first line
drugs may be considered
as initial therapy if the
blood pressure is >20
mmHg systolic or >10
mmHg diastolic above
target
> 2-drug
combinations
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an
ACEI or ARB
Combinations of an ACEI with an ARB are specifically not recommended in the absence
of proteinuria
More than 3 drugs may be needed to reach target values
If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a
loop diuretic should be substituted for a thiazide diuretic if control of volume is desired
2013
Vascular Protection Checklist
 A • A1C – optimal glycemic control (usually ≤7%)
 B • BP – optimal blood pressure control (<130/80)
 C • Cholesterol – LDL ≤2.0 mmol/L if decided to
treat
 D • Drugs to protect the heart
A – ACEi or ARB │ S – Statin │ A – ASA if indicated
 E • Exercise – regular physical activity, healthy diet,
achieve and maintain healthy body weight
 S • Smoking cessation
Chronic Kidney Disease (CKD)
Checklist
2013
 SCREEN regularly with random urine albumin creatinine ratio
(ACR) and serum creatinine for estimated glomerular
filtration rate (eGFR)
 DIAGNOSE with repeat confirmed
ACR ≥2.0 mg/mmol and/or eGFR <60 mL/min
 DELAY onset and/or progression with glycemic and blood
pressure control and ACE-inhibitor or Angiotensin Receptor
Blocker (ARB)
 PREVENT complications with “sick day management”
counselling and referral when appropriate
2013
ACR ≥2.0 mg/mmol
CKD
in Diabetes
and / or
eGFR <60 mL/min
Stages of Diabetic Nephropathy
Note: change in definition of microalbuminuria
ACR ≥2.0 mg/mmol
2013
Beware of Transient Albuminuria
Reducing Progression of Diabetic
Nephropathy
• Optimal glycemic control
• Optimal blood pressure control
• ACE-inhibitor (ACEi) or Angiotensin
Receptor Blocker (ARB)
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
Counsel all
Patients
About
Sick Day
Medication
List
2013
Retinopathy Screening Reduces Risk
of Blindness (T1DM)
Retinopathy is rare in prepubertal children
Screen annually in T1DM, 5 years after onset in
individuals ≥15 years of age
Screening Reduces Risk of Blindness
(T2DM)
Retinopathy may be present in 21-39% of patients with
T2DM at diagnosis
Screen every 1-2 years in T2DM
beginning at diagnosis
2013
Retinopathy Checklist
SCREEN regularly
DELAY onset and progression with glycemic
and blood pressure control ± fibrate
TREAT established disease with laser
photocoagulation, intra-ocular injection of
medications or vitreoretinal surgery
FIELD: Retinopathy Requiring Laser
10
Cumulative risk (%)
8
HR = 0.70
95% CI = 0.58–0.85
p = 0.0003
6
Placebo
4
Fenofibrate
2
0
0
1
2
3
4
Years from randomization
FIELD Study Investigators. Lancet 2005 ; 366 (9500): 1849-61
5
6
Risk Factors for Progression
•
•
•
•
•
•
•
•
Longer duration of diabetes
Elevated A1C
Hypertension
Dyslipidemia
Low hemoglobin level
Pregnancy (with T1DM)
Proteinuria
Severe retinopathy itself
Neuropathy
In people with type 2 diabetes, screening
for peripheral neuropathy should begin at
diagnosis of diabetes and occur annually
thereafter. In people with type 1 diabetes,
annual screening should commence after
5 years’ postpubertal duration of diabetes
[Grade D, Consensus].
40-50% of People with DM will have
Detectable Neuropathy within 10 years
• Sensorimotor poly- or mono-neuropathy
• Increased risk for:
– Foot ulceration and amputation
– Neuropathic pain
– Significant morbidity
– Usage of health care resources
Risk Factors
•
•
•
•
•
Elevated blood glucose
Elevated triglycerides
High BMI
Smoking
Hypertension
Screening
Refer to neurology if non-diabetic
neuropathy is suspected
Neuropathy
• Screen
– 5 years after dx for Type 1 diabetes
– At dx for Type 2 diabetes
• Method
– Vibration sense on big toe
– Monofilament testing
• Treatment
– Optimize glycemic control
– Antidepressant, anticonvulsants, opioids, topical agents
can be considered
Foot care
• By individual AND health care professional
• Screening at least annually and more often if high
risk
• Evaluate for structural abnormalities, neuropathy,
PVD, ulcerations, infection
• If high risk, provide foot care education,
professionally fitted footwear, early referral to
professional trained in foot care
• Advise to stop smoking
• If foot ulcer is present, need multidisciplinary team
Question
• What percentage of people with diabetes and
established coronary artery disease have NO
chest pain/symptoms of angina?
1) 10-30%
2) 20-50%
3) 40-70%
4) 50-80%
Screening for Coronary Artery Disease
(CAD) Checklist
2013
SCREEN with baseline resting ECG in select
patients
STRESS TESTING for patients with
symptoms or other associated diseases
REFER patients with inducible ischaemia to
a cardiac specialist
Who Should be Screened with ECG?
Age >40 years
Duration of DM
>15 years +
Age >30 years
End organ damage
– Microvascular
– Macrovascular
Cardiac risk factors
Baseline resting
ECG
Repeat every 2 years
Who Should have Stress Testing and/or
Functional Imaging to Screen for CAD?
Typical or atypical cardiac
symptoms
Associated diseases:
–
–
–
–
PAD
Carotid bruits
TIA
Stroke
Resting ECG
abnormalities (e.g. Q waves)
Exercise ECG
stress testing
If cannot exercise or
resting ECG abnormality
present:
–
–
Pharmacologic stress
echo
Pharmacologic stress
nuclear imaging
Special populations …
2013
Diabetes in the Elderly Checklist
 ASSESS for level of functional dependency (frailty)
 INDIVIDUALIZE glycemic targets based on the above (A1C ≤
8.5% for frail elderly) but if otherwise healthy, use the same
targets as younger people
 AVOID hypoglycemia in cognitive impairment
 SELECT antihyperglycemic therapy carefully
 caution with sulfonylureas or thiazolidinediones
 Basal analogues instead of NPH or human 30/70 insulin
 Premixed insulins instead of mixing insulins separately
 GIVE regular diets instead of “diabetic diets” or nutritional
formulas in nursing homes
Add an agent best suited to the individual (agents listed in alphabetical order):
Class
Relative
A1C
Lowering
Hypoglycemia
Weight
-glucosidase inhibitor
(acarbose)

Rare
Neutral
to 
Improved postprandial control, GI
side-effects

 to
Rare
Rare
neutral

•

Yes

Incretin agents:
DPP-4 Inhibitors
GLP-1 receptor
agonists
Insulin
Insulin secretagogue:
Meglitinide
Sulfonylurea


Yes*
Yes


Thiazolidinediones

Rare

Weight loss agent
(orlistat)

None

Other therapeutic considerations
Cost
$$
May use detemir or glargine instead of$$$
NPH or human 30/70 for less hypos $$$$
GI side-effects
• Premixed insulins and prefilled insulin
pens instead of mixing insulin to reduce
No dose
ceiling,
$-$$$$
dosing
errorsflexible regimens
• CAUTION
in the elderly
*Less
hypoglycemia
in context of
• Initial
doses
= HALF
ofrequires
usual dose
missed
meals
but
usually
$$
• Avoid
TID
to QIDglyburide
dosing
$
• Use gliclazide,
gliclazideassociated
MR, glimepiride,
Gliclazide
and glimepiride
or repaglinide
withnateglinide
less hypoglycemia
than instead
glyburide
• CAUTION
in the elderly
CHF,
edema, fractures,
rare bladder
• Increased
risk of fractures
cancer
(pioglitazone),
cardiovascular
• Increased(rosiglitazone),
risk of heart failure
controversy
6-12
weeks required for maximal effect
$$
GI side effects
$$$
Need a PRECONCEPTION
checklist for women with preexisting diabetes
 1. Attain a preconception A1C of ≤ 7.0% (if safe)
 2. Assess for and manage any complications
 3. Switch to insulin if on oral agents
 4. Folic Acid 5 mg/d: 3 mo pre-conception to 12
weeks post-conception
 5. Discontinue potential embryopathic meds:
 Ace-inhibitors/ARB (prior to or upon detection of
pregnancy)
 Statin therapy
2013
OBJECTIVES/SUMMARY
• 1. Review highlights from the 2013 Canadian
Diabetes Association Guidelines including
diagnostic criteria and treatment goals
• 2. Discuss anti-hyperglyemic agent options
after Metformin, focussing on newer
medication options
• 3. Explore the complications of Diabetes and
examine vascular protective strategies in
individuals with Diabetes
THANK YOU!