2. Development Committee
CHAIR
Lawrence A. Leiter, Endocrinology & Metabolism, University of Toronto, Toronto
STEERING COMMITTEE
Harpreet S. Bajaj, Endocrinology & Metabolism, LMC Diabetes & Endocrinology, Brampton 
C. Keith Bowering, Diabetologist, Internal Medicine, University of Alberta, Edmonton 
Alice Y. Y. Cheng, Endocrinology & Metabolism, University of Toronto, Toronto
Jean-Marie Ekoé, Endocrinology & Metabolism, Université de Montréal, Montreal 
Pierre Filteau, General Practice, Saint-Marc-des-Carrières 
Stewart B. Harris, Family Medicine, Epidemiology & Biostatistics, Western University, London 
Ronald M. Goldenberg, Endocrinology & Metabolism, LMC Diabetes & Endocrinology, Thornhill 
Vincent C. Woo, Endocrinology & Metabolism, University of Manitoba, Winnipeg 
Jean-François Yale, Endocrinology & Metabolism, McGill University, Montreal 
EDUCATIONAL COMMITTEE
Carl Fournier, Family Physician, Montreal 
Theodore J. Jablonski, Family Physician, Calgary 
Kevin K. Saunders, Family Physician, Winnipeg 
Richard Ward, Family Physician, Calgary

3. Faculty/Presenter Disclosure
Faculty: [Speaker’s name]
Relationships with commercial interests:
Grants/Research Support:
Speakers Bureau/Honoraria:
Consulting Fees:
Other:
Please fill in your disclosures on the following slides and take a moment to review them before beginning the presentation.

4. Disclosure of Commercial Support
This program has received financial support from Merck Canada Inc. in the form of an educational grant.
This program has received in-kind support from Merck Canada Inc. in the form of logistical support.
Potential for conflict(s) of interest:
[Speaker name] has received [payment/funding, etc.] from Merck Canada Inc.
Merck Canada Inc. benefits from the sale of the products that will be discussed in this program: Sitagliptin (Januvia®), Combination Sitagliptin/Metformin (Janumet®).

5. Mitigating Potential Bias
The information presented in this CME program is based on recent information that is explicitly “evidence-based.”
This CME Program and its material is peer-reviewed, and all the recommendations involving clinical medicine are based on evidence that is accepted within the profession. All scientific research referred to, reported or used in the CME/CPD activity in support or justification of patient care recommendations conforms to the generally accepted standards.

6. Objectives Following this program, participants will be able to:
Identify glycemic targets for elderly patients with T2DM
Identify challenges with polypharmacy in elderly patients with T2DM
Provide solutions to these challenges

7. Case 3 82-year-old recent widow Depression (due to passing of husband)
T2DM duration: 15 years
Dyslipidemia
Poor diet routine
BP: 145/85 mmHg
Does not leave the house much
History of CAD/CHF
MI 5 years ago with stent
Osteoarthritis
Medications
Metformin + SU
Naproxyn + PPI
Statin
Citalopram
ACEi, Furosemide
Plavix
Β-blocker
Tylenol with codeine
Labs
A1C 8.1%
eGFR 56 mL/min/1.73m2
TC, LDL-C, TG
Speaker’s Notes
Review patient’s case history

8. Scenario
Daughter called EMS when she dropped by for a visit and found mother on the floor
Glucose level at ER was 3.1 mmol/L

9. Scenario
The patient was discharged from the ER with instructions to “see your family doctor and get your diabetes pills straightened out.”
She presents accompanied by her daughter with a “bag of pills.” You note that some of the pills were left over from medications stopped 3 years ago.
Her daughter has moved in to stay with her but works outside of the house – she “wants to get things straightened out.”

10. Case 3
What are the potential causes of the fall?

11. Definition of Hypoglycemia
Development of neurogenic or neuroglycopenic symptoms
Neurogenic (autonomic)
Neuroglycopenic
Trembling
Difficulty concentrating
Palpitations
Confusion
Sweating
Weakness
Anxiety
Drowsiness
Hunger
Vision changes
Nausea
Difficulty speaking
Dizziness
Speaker’s Notes
The CDA defines hypoglycemia as the development of autonomic symptoms, (trembling, palpitations, sweating, anxiety, hunger, nausea, tingling) or neuroglycopenic (difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache, dizziness) a low plasma glucose, and symptoms responding to the administration of a carbohydrate. In mild to moderate hypoglycemia, blood glucose is <4 mmol/L, autonomic and/or neuroglycopenic symptoms are present, but the patient is able to self-treat. However, patients who maintain a higher blood glucose level may experience hypoglycemia at levels >4.0 mmol/L. Severe hypoglycemia indicates the patient is unable to treat the reaction without outside assistance. He/she may or may not be conscious.
Low blood glucose (<4 mmol/L if on insulin or secretagogue)
Response to carbohydrate load
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2013;37:S69-71.

12. Recognize Risk Factors for Severe Hypoglycemia
Risk factors in T2DM patients
Elderly
Poor health literacy, food insecurity
Increased A1C
Duration of insulin therapy
Severe cognitive impairment
Renal impairment
Neuropathy
Speaker’s Notes
Severe hypoglycemia refers to hypoglycemia resulting in individuals requiring assistance – typical with a PG of less than 2.8.
Teaching caregivers to administer glucagon should be undertaken, especially in patients with risk factors for severe hypoglycemia.
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2013;37:S69-71.

13. Case 3
What is the patient’s target A1C?

14. Individualizing A1C Targets
≤7%
>7% 7%
A target ≤ 6.5% may be considered in some patients with type 2 diabetes to further lower the risk of nephropathy and retinopathy which must be balanced against the risk of hypoglycemia
Consider % if:
Most patients
with type 1 and type 2 diabetes
Limited life expectancy
High level of functional dependency
Extensive coronary artery disease at high risk of ischemic events
Multiple co-morbidities
History of recurrent severe hypoglycemia
Hypoglycemia unawareness
Longstanding diabetes patient for whom it is difficult to achieve an A1C≤7%, despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy
Speaker’s Notes
Intensive glucose control, lowering A1C values to 7% provides strong benefits for microvascular complications and, if achieved early in the disease, might also provide a significant macrovascular benefit, especially as part of a multifactorial treatment approach.
More intensive glucose control, A1C 6.5%, may be sought in patients with a shorter duration of diabetes, no evidence of significant CVD and longer life expectancy, provided this does not significantly increase hypoglycemia.
An A1C target of 8.5% may be more appropriate in patients with limited life expectancy, a higher level of functional dependency, a history of severe hypoglycemia, advanced comorbidities, and failure to attain established glucose targets despite treatment intensification.
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2013;37:S31-34.

15. Case 3
How would you adjust her antihyperglycemic therapy?

16. 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
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2013;37:S

17. Frailty Speaker’s Notes
“Frailty” refers to a multidimensional syndrome culminating in increased vulnerability. This slide shows the Clinical Frailty Scale that helps define how frail an individual is on a 9-point scale (very fit to terminally ill).
Frailty is a better morbidity and mortality indicator than chronological age or co-morbidities, and elderly individuals with diabetes are more likely to be frail.
Frailty is accordingly an important criterion to assess before determining how aggressive glycemic lowering should be and how low an A1C should be targeted.

18. Mini-Cog Instructions
3 minute test to screen for cognitive defects in the elderly
2 – 3 times faster than MMSE (Mini-Mental State Examination)
Not affected by language, ethnicity or socioeconomic level
1. Remember these 3 words:
- Blue
- Apple
- Train
2. Draw a clock with the arms at
- 11h10
3. What are the 3 words?
Speaker’s Notes
The Mini-Cog is a composite of three-item recall and clock drawing. It was developed as a brief test for discriminating demented from non-demented persons in a community sample of culturally, linguistically and educationally heterogeneous older adults. Importantly, it requires minimal language interpretation and training to administer, and no test forms of scoring modifications are needed to compensate for the extensive linguistic and educational heterogeneity of the sample. Notably, the Borson et al. study demonstrated that the Mini-Cog had the highest sensitivity (99%) and correctly classified the greatest percentage (96%) of subjects when compared against the Mini-Mental State Exam (MMSE) and Cognitive Abilities Screening Instrument (CASI).
Borson S. The mini-cog: a cognitive “vital signs” measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry 2000; 15(11):1021

19. Mini-Cog Scoring Algorithm
3-item recall
1 or 2 3
Probable
dementia
Unlikely
dementia
Clock abnormal*
Clock normal*
Speaker’s Notes
The slide provides details on the scoring system used for the mini-cog system. The lower the recollection score, the more likely the patient is suffering from dementia. The ability to draw a cohesive clock face with the hands demonstrating 11:10 is also critical in the assessment process.
Probable
dementia
Unlikely
dementia
*Clock drawing considered normal if all numbers are present and in the correct sequence and position, and the hands readably display the requested time.
Borson S, et al. Int J Geriatr Psychiatry 2000;15:

20. Add-on to sulfonylurea or Insulin
Hypoglycemia
SECRETAGOGUES
If possible, switch to an incretin agent or an SGLT2 inhibitor
Provide/refer for education on nutrition, physical activity, alcohol
If staying on secretagogue
Decrease dose
Use gliclazide or glimepiride in the morning (discuss timing) rather than glyburide
Use repaglinide if skipping meals
Verify eGFR
Reduce dose or discontinue if patient becomes ill
Add-on to sulfonylurea or Insulin
Consider reducing SU/insulin dose when adding DPP-4 inhibitor, GLP-1R agonist or SGLT2 inhibitor if the A1C is not very high
Recognize and educate on the variability in glucose levels
SU, INSULIN & DRIVING
Consider switching to
another class
The patient should be advised to:
Test glucose levels before
driving and every 4 hours if
s/he is taking a long trip
Keep a meter and source
of carbohydrate handy
NOT drive if blood glucose
is under 5.0 mmol/L
Pull over if experiencing
symptoms of hypoglycemia
NOT drive for an hour
even after an occurrence
of mild hypoglycemia
Speaker’s Notes
Hypoglycemia is a major concern in elderly individuals with type 2 diabetes, and medication-induced hypoglycemia is the most common cause of hypoglycemia.
This slide provides recommendations on strategies to help minimize the occurrences of hypoglycemic events.
Adapted from Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2013;37 Suppl 1.

21. Antihyperglycemic Agents and Renal Function
<15 5
15-29 4
30-59 3
≥90 1
60-89 2
CKD Stage
eGFR
(mL/min/1.73m2) 25
Acarbose 30 60
Metformin 50
6.25 mg
12.5 mg
Alogliptin 15
Linagliptin
2.5 mg
Saxagliptin
25 mg
50 mg
Sitagliptin
Exenatide(BID/QW)
Albiglutide
Dulaglutide
Liraglutide
Gliclazide/Glimepiride
Glyburide
Repaglinide 45
60*
Canagliflozin
Dapagliflozin
Empagliflozin
Thiazolidinediones
Contraindicated
Not recommended
Caution and/or dose reduction
No dose adjustment but dose
monitoring of renal function
Safe
Do not initiate if
GFR <60 mL/min/1.73m2
SGLT2
inhibitors
secretagogues
Insulin
GLP-1 receptor
agonists
DPP-4
Biguanide
ɑ-Glucosidase
inhibitor
Speaker’s Notes
This slide outlines the renal function considerations associated with each of the currently approved antihyperglycemic agents in Canada.
100 mg
10 or 25 mg
Adapted from: Product Monographs as of Nov. 2016; Harper W et al. Can J Diabetes 2015;39:

22. Make timely adjustments to attain target A1C within 3-6 months
Add another class of agent best suited to the individual (classes listed in alphabetical order):
Class
Relative A1C Lowering
Hypo-
glycemia
Weight
Effect in Cardiovascular Outcome Trial
Other Therapeutic considerations
Cost
Alpha-glucosidase inhibitor (acarbose) 
Rare
Neutral to 
Improved postprandial control, GI side-effects $$
DPP-4 inhibitors 
Alo, saxa, sita: neutral
Caution with saxagliptin in heart failure
$$$
GLP-1R agonists
 to 
Lira: superiority in T2DM patients with clinical CVD
Lixi: neutral
GI side effects
$$$$
Insulin

Yes 
Glar: neutral
No dose ceiling, flexible regimens
$-$$$$
Insulin secretagogue: Meglitinide
Sulfonylurea 
Less hypoglycemia in context of missed meals but usually requires TID to QID dosing
Gliclazide and glimepiride associated with less hypoglycemia than glyburide $
SGLT2 inhibitors
Empa: superiority in T2DM patients with clinical CVD
Genital infections, UTI,
hypotension, dose-related changes in LDL-C, caution with renal dysfunction and loop diuretics, dapagliflozin not to be used if bladder cancer, rare diabetic ketoacidosis (may occur with no hyperglycemia)
Thiazolidinediones
Neutral
CHF, edema, fractures, rare bladder cancer (pioglitazone), cardiovascular controversy (rosiglitazone), 6-12 weeks required for maximal effect
Weight loss agent (orlistat)
None
alo=alogliptin; empa-empagiflozin; glar-glargine; lixi-lixisenatide; saxa-saxagliptin; sita-sitagliptin L I F E S T Y
Speaker’s notes
Concept of RELATIVE A1C lowering – not absolute
Concept of RELATIVE cost considerations
Change to achieve target within 3 to 6 months
If not at glycemic target
 Add another agent from a different class  Add/intensify insulin regimen
Make timely adjustments to attain target A1C within 3-6 months
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Pharmacologic Management of Type 2 Diabetes: 2016 Interim Update. Can J Diabetes. 2016;40:

23. Case 3
How would you improve adherence?

24. Improving Adherence Recommend home care
Reduce pill burden through fixed dose combination (FDC)
Review medications – does she still require all the medications she has been taking?
Blister packs
Work with a community pharmacist to monitor adherence
Get rid of old medications
Consider a geriatric assessment
Screen for depression/cognitive impairment/substance abuse

25. Mean Difference in HbA1C (FDC – CDT)
Fixed Dose Combination Therapy is Associated with Improved Glycemic Control
Mean difference of A1C (95% CI)
Study
Weight (%)
Baseline A1C
Blonde L et al, 2003
-0.53% (-0.80, -0.26)
28.0%
9.1–9.2%
Thayer S et al, 2010
-0.31% (-0.66, -0.04)
22.7%
8.0–8.1%
Thayer S et al, 2010
-0.45% (-0.77, -0.13)
24.7%
7.3–7.8%
Duckworth W et al, 2003
-0.60% (-0.97, -0.23)
21.4%
8.3%
Raptis AE et al, 1990
-2.30% (-3.65, -1.00)
3.2%
10.6%
Speaker’s Notes
This was a systematic review and meta-analysis that compared the effects fixed-dosed combinations (FDCs) and co-administered dual therapy (CDT) had on A1C outcome and medication adherence in individuals with type 2 diabetes.
Ten articles met inclusion criteria. Total sample size was 70,573 patients
The forest plot shows the difference in A1C levels between patients with type 2 diabetes who were on FDCs vs. those on CDT.
A1C levels were significantly lower in individuals who were on FDCs.
Mean differences in A1C between the two groups were -0.53% [95% CI: -0.78, -0.28]; (p < 0.0001).
Note: A shortcoming of this analysis was that it included studies with very different patient characteristics, e.g. baseline A1C ranged from the low 7s to the mid 10s.
Not shown here but also reported in the same paper was the revelation that medication adherence (using medication possession ratio as a surrogate) was significantly higher among individuals who were taking FDCs vs CDT.
Blonde L (2003) compared glyburide/metformin FDC to glyburide co-administered with metformin
Thayer S (2010) compared switch to rosiglitazone/glimepiride FDC from monotherapy or dual therapy with a TZD and/or a SU
Duckworth (2003) compared switch from sulfonylurea co-administered with metformin to glyburide-metformin FDC
Raptis (1990) compared glibenclamide or glibenclamide-phenformin FDC with those of gliclazide, chlorpropamide or biguanides
Overall
-0.53% (-0.78, -0.28)
100% -4
-3.5 -3
-2.5 -2
-1.5 -1
-0.5
0.5
Mean Difference in HbA1C (FDC – CDT)
Favours FDC
CDT = coadministered dual therapy; FDC = fixed-dosed combination
Adapted from Han S et al. Curr Med Res Opin ;28(6):

26. Case 3
Why is hypoglycemia an important concern among the elderly?

27. Older Patients Have Less Perception of Hypoglycemia14 ** 12 10
Middle-aged (39-64 years)
Autonomic symptoms 8 6
Older (≥ 65 years) 4 2
Baseline
Hypo
Recovery 12 * 10
Speaker’s Notes
The increased risk of hypoglycemia in elderly individuals appears to be due to an age-related reduction in glucagon secretion, impaired awareness of hypoglycemic warning symptoms and altered psychomotor performance, which prevents such patients from taking steps to treat hypoglycemia.
These graphs detail the autonomic and neuroglycopenic symptom scores in individuals with type 2 diabetes ≥65 years (older) and years (middle-aged) following an induced 30-min hypoglycemic state (2.8 mmol/L). In contrast to the older individuals, middle aged participants demonstrated a pronounced increase in both scores at the end of the hypoglycemic plateau (both p < 0.01). Counter-regulatory hormone levels were similar in the two groups.
Autonomic symptoms taken into account: anxiety, palpitation, hunger, sweating, irritability and tremor
Neuroglycopenic symptoms taken into account: dizziness, tingling, blurred vision, difficulty concentrating and faintness
Notably 7/13 middle-aged but only 1/13 older participant correctly estimated their blood glucose concentration to be <3.3 mmol/L during the hypoglycemic episode (p = 0.011). 8
Neuroglycopenic symptoms 6 4 2
Baseline
Hypo
Recovery
*P < **P <0.01
Bremer JP et al. Diabetes Care. 2009; 32 (8): 27

28. Frequency of Emergency Room Visits for Hypoglycemia by Age
Emergency room visits (USA) for hypoglycemia according to patient age, n
Total estimated number of cases (95% CI)
Rate per 1000 subjects for diabetic pop.
(95% CI)
Rate per 1000 visits at the emergency (95% CI)
Total
1303
4960 (4460, 5460)
34 (30, 37)
3.7 (3.4, 4.1)
Age (years)
<45
401
1550 (1330, 1780)
62 (53, 71)
1.7 (1.5, 2.0)
0-19 78
359 (229, 489) –
0.9 (0.6, 1.2)
20-44
323
1200 (1020, 1370)
2.3 (2.0, 2.7)
45-64
364
1230 (1060, 1400)
19 (17, 22)
5.5 (4.7, 6.2)
65-74
219
845 (698, 991)
25 (20, 29)
10 (8.5, 12)
75
319
1330 (1090, 1580)
54 (44, 64)
12 (9.4, 14)
Speaker’s Notes
Older patients with diabetes are more likely than younger patients to experience an episode of hypoglycemia requiring a visit to the emergency department.
These investigators analyzed data from the U.S. National Hospital Ambulatory Medical Care. They observed about 5 million emergency department visits for hypoglycemia during this time period, 25% of which resulted in hospital admission. The visit rate per 1,000 among the diabetic population was 34 (95% CI 30-37). Visit rates were higher in patients aged < 45 years (n = 62) and ≥ 75 years (n = 54) versus those aged years (n = 21).
Note: this table represents data gathered from the American National Hospital Ambulatory Medical Care between 1993 and 2005.
USA = United States of America; CI = confidence interval
Ginde AA et al. Diabetes Care 2008; 31:511-3.

29. Among Frail Elderly Parameter Target A1C ≤8.5% FPG or
preprandial glucose
mmol/L (depending on level of frailty)
AVOID HYPOGLYCEMIA
Speaker’s Notes
Among frail elderly individuals, an A1C target 8.5% may be more appropriate. It is important to personalize A1C target to avoid hypoglycemia.
FPG = Fasting Plasma Glucose
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2013;37:S1-21.

30. Steps to Address Hypoglycemia
Recognize autonomic or neuroglycopenic symptoms
Confirm if possible (blood glucose < 4.0 mmol/L)
Treat with “fast sugar” (simple carbohydrate) (15 g) to relieve symptoms
Retest in 15 minutes to ensure BG > 4.0 mmol/L and re-treat (see above) if needed
Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein
Speaker’s Notes
The goals of treatment for hypoglycemia are to detect and treat a low blood glucose level promptly by using an intervention that provides the fastest rise in blood glucose to a safe level, to eliminate the risk of injury and to relieve symptoms quickly.
Teaching patients to recognize and treat hypoglycemia can be done in 5 steps.
It is important to teach patients to recognize the common autonomic and neuroglycopenic symptoms associated with hypoglycemia.
Common autonomic symptoms include: trembling, palpitations, sweating, anxiety, hunger, nausea and tingling
Common neuroglycopenic symptoms include: difficulty concentrating, confusion, weakness, vision change and headache
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2015;39:250-2.

31. Conclusions Relax glycemic targets in high-risk patients
Harm reduction in the elderly mandates prevention of hypoglycemia
Regularly review medications, environmental and social conditions, cognitive function and adherence in the elderly