The document discusses diabetes management in elderly patients, focusing on glycemic control, complications, and treatment strategies. It presents findings from studies on optimal A1C targets for older adults and compares the effectiveness of insulin therapy regimens in improving glycemic control while minimizing hypoglycemia. The conclusion suggests a target A1C of <8.0% for older patients and highlights the advantages of adding insulin to oral agents over using premixed insulin alone.

1. Diabetes In Elderly
Patients
Trina La
PharmD. Candidate
University of Georgia
College of pharmacy

2. Outline
 Introduction
 Study 1: Glycemic control, complications, & death
in older diabetic patients
 Study 2: Combination of oral antibiabetic agents
with basal insulin versus premixed insulin
ALONE in randomized elderly patients with Type
2 DM
 Summary of oral antidiabetic agents and insulins
 Conclusion

3. Introduction
 Definition
 DM is a syndrome characterized by chronic
hyperglycemia & disturbances of carbohydrate, fat &
protein metabolism, associated with an absolute or
relative deficiency in insulin secretion and/or insulin
action
 Associated problems affecting management in elderly
 Cerebral aging
 Atherosclerotic changes
 Compromised Cardio Respiratory Reserve
 Cataract
 Neuropathy
 Cerebral Vascular Disease

4. Diabetic Complications
4
Amputation
Microvascular
Complications
Neuropathy
Cerebrovascular
Disease
Peripheral Vascular
Disease
Macrovascular Complications
Retinopathy
Nephropathy
Heart Disease
Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986. Stratton IM et al. BMJ.
2000;321:405-412 with permission from the BMJ Publishing Group www.cdc.gov.
Amputation

5. Glycemic Control, Complications, and Death in Older
Diabetic Patients
ELBERT HUANG, JENNIFER LIU, HOWARD
MOFFET, ET AL
Diabetes care 2011;34: 1329-1335
Funded by the institute of diabetes & digestive & kidney diseases

6. Background
 People aged > 60 years comprise > 40% of the type 2
diabetic population in the U.S, yet identifying the
optimal glucose control level for older patients with
diabetes remains a significant challenge
 Recommended glycemic targets
 A1C <6.5% from American Association of Clinical
Endocrinologists
 A1C <7.0% from the American Diabetes Association
 A1C < 8.0% from geriatric diabetes care guidelines for
older patients with limited life expectancy
 However, there has been limited evidence for any of
these targets of glycemic control for elderly patients

7. Objective
 To identify the range of glycemic levels
associated with the lowest rates of complications
& mortality in older diabetic patients

8. Outcomes
 Acute metabolic events
 Hospitalizations for diabetes with other coma
 Diabtes with hyperosmolarity
 Diabetes with ketoacidosis
 Uncontrolled diabetes
 Chronic microvascular event
 End-stage renal disease
 Amputation
 Severe diabetic eye disease
 Chronic cardiovascular events
 Coronary artery disease
 Congestive heart failure
 Cerebralvascular disease
 Peripheral vascular disease

9. Research Design & Methods
Inclusion Criteria Exclusion Criteria
 Type 2 diabetes
 Aged 60 years
≥
 Continuous Kaiser
membership & pharmacy
benefits for at least 12
months before baseline
 Type 1 diabetes or
unknown diabetes
 End-stage renal disease
 No A1C test result during
the year prior to baseline

10. Research Design & Methods
 A restrospective cohort study (2004-2008) of
71,092 patients with type 2 diabetes, age 60
≥
years, enrolled in Kaiser Permanente Northern
California
 Registry eligibility is based on
 Pharmacy records
 Laboratory data
 Outpatient
 Emergency room
 Hospitalization diagnose of diabetes

11. Research Design & Methods
 A restrospective cohort study (2004-2008) of
71,092 patients with type 2 diabetes, age 60
≥
years, enrolled in Kaiser Permanente Northern
California
 Registry eligibility is based on
 Pharmacy records
 Laboratory data
 Outpatient
 Emergency room
 Hospitalization diagnose of diabetes

12. A1C & Assessment of covariates
 For stratified analyses
 A1C
 Assessment of covariates
 Demographics
 Duration of diabetes
 Systolic blood pressure
 Lab findings within 1 year prior to baseline:
 eGFR, urinary albumin excretion, BMI; prevalent complications &
comorbidities ( hx of lower extremitiy amputation, photocoagulation)
 Hospitalization for acute metabolic event, MI, stroke, CHF, ect
 Smoking
 Baseline use of glucose-lowering medications

13. Results
 The mean age of population: 71 years
 Population: ethnically diverse
 The mean A1C: 7.0%
 The mean duration of diabtes: 8.3 years
 Patients with lower baseline A1C values tend to be
 Older
 More likely to be non-Hispanic white
 More likely to have a shorter duration of diabetes
 Better cholesterol control
 Lower GFR
 Less evidence of other microvascular complication
 Much less likely to be treated with insulin

14. Results: Baseline A1C, Complications, &
mortality; Overall population results
Outcome Incidence
Density
(Events/1000
person-years)
Model A1C
<6.0 6.0-6.9 7-7.9 8.-8.9 9-9.9 10-
10.9
≥11
Acute metabolic
event
1.23 Adjusted HR
95% CI
1 1.44
.82-2.53
2.35
1.3-4.2
3.82
2.0-7.2
4.95
2.5-10
6.60
3-14.6
11.5
5.7-23.5
Chronic
microvascular
event
26.68 Adjusted HR
95% CI
1
1
1.11
.99-1.3
1.25
1.1-1.4
1.53
1.3-1.8
1.52
1.3-1.8
1.72
1.4-2.1
2.04
1.7-2.47
Chronic
cardiovascular
events
47.15 Adjusted HR
95% CI
1
1
1.09
1.0-1.2
1.14
1.1-1.2
1.26
1.1-1.4
1.28
1.1-1.5
1.39
1.2-1.7
1.77
1.51-2.1
Mortality 40.42 Adjusted HR
95% CI
1
1
0.84
0.8-0.9
0.83
0.7-0.9
0.90
0.8-1
1.02
0.9-1.2
1.21
1.0-
1.45
1.31
1.09-1.6
Any complication 69.90 Adjusted HR
95% CI
1
1
1.09
1.0-1.2
1.18
1.1-1.3
1.38
1.3-1.5
1.42
1.3-1.6
1.52
1.3-1.7
1.8
1.6-2.16
Any complication
or Death
97.97 Adjusted
HR95% CI
1
1
0.98
.93-1.03
1.03
.97-1.1
1.20
1.1-1.3
1.26
1.1-1.4
1.35
1.2-1.5
1.63
1.5-1.8

15. Age-stratified results Adjusted analyses
Outcome
Baseline A1C
<6.0 6.0-6.9 7.0-7.9 8.0-8.9 ≥9
Mortality
Age-group
60-69
70-79
≥80
1
1
1
0.92
0.83
0.83
0.83
0.85
0.83
0.91
0.86
1.05
1.17
1.11
1.20
Any
complication
60-69
70-79
≥80
1
1
1
1.12
1.08
1.11
1.20
1.21
1.18
1.44
1.35
1.28
1.58
1.50
1.43
Any
complication
60-69
70-79
≥80
1
1
1
1.04
0.98
0.94
1.08
1.07
0.96
1.28
1.18
1.13
1.43
1.36
1.25

16. Conclusions
 Observed relationships between A1C & combined
end points support setting a target of A1C< 8.0%
for older patients
 A1C <6.0% were associated with increase
mortality risk
 Additional research is needed to evaluate the low
A1C-mortality relationship
 Ongoing research on care individualization in
the elderly suggest that life expectancy, comorbid
conditions, patient preferences are important
consideration in glycemic control

17. Combination of Oral Antidiabetic Agents
with Basal Insulin versus Premixed Insulin
ALONE in Randomized Elderly Patients
with Type 2 Diabetes Mellitus
Janka Hans, Plewe gerd, Busch klaus
Jags 2007;55:182-188
Funded by a research grant from sanofi-aventis

18. Background
 The association between poor glycemic control & the
occurrence of micro-& macrovascular complications has been
demonstrated in patients with type 1 & 2 DM
 Tight glycemic control may be associated with greater
frequency of hypoglycemic episodes; however it can have
serious clinical consequences
 Consensus opinion on how & when to initiate insulin tx in
patients with type II DM is lacking
 In older patients with type 2 DM, it is important that the
insulin regimen be easy to apply, with optimal efficacy &
safety.
 Few studies have directly compared the leading methods of
insulin initiation in this population

19. Objectives
 To compare initiation of insulin therapy by
adding once-daily Lantus to oral antidiabetic
agents(OAD) with premixed insulin alone

20. Design
 A parallel-group, open-label, randomized,
multinational clinical trial with a 1 to 4 week
screening phase & a 24-week treatment phase
 A 1:1 randomization schedule stratified by center
sequentially assigned treatment codes to eligible
patients

21. Inclusion & Exclusion Criteria
Inclusion Criteria Exclusion Criteria
 Aged 65 & older
 Type II DM for at least 1
year
 Treated with a stable dose
of Sulfonylurea &
Metformin for at least 1
month
 BMI 35 kg/m
≤ 2
 7.5
A1C 10.5
≤ ≤
 Fasting blood glucose(FBG) 120mg/dL
≥
 Any additional use of
other oral blood glucose-
lowering agents
 Prior use of insulin
exceeding 3 days
 A history of ketoacidosis

22. Study Protocol & Treatment
 Previous Sulfonylurea therapies were replaced with
3 or 4 mg glimepiride during the screening phase
 Metformin ( 850mg) administered during the study
≥
was provided & taken at the same dose as before
study entry
 The dose of Glimepiride & Metformin remained
unchanged throughout the study
 At the baseline visit, patients were randomly
assigned to insulin Lantus given once daily in AM in
combination with Glimepiride & Metformin or to
human premixed insulin (70/30) BID

23. Study Protocol & Treatment
 For both groups, the FBG target was 100mg/dL
 FBG values & pre-dinner BG as well as
hypoglycemic episodes were recorded in a
standardized diary
 Hematological, clinical chemistry, & HbA1c
values at baseline & 12, & 24 weeks were
measured
 The participating investigators noted any
adverse events at every visit or telephone
contact

24. Efficacy & Safety Measurements
 The primary efficacy measure was change in A1C
level from baseline to endpoint
 Secondary efficacy measurement:
 Mean FBG levels
 Mean daytime BG levels
 Mean BG values from the 8-point profile
 The proportion of patients with FBG levels of 100mg/dL
 The proportion of patients with A1C levels of 7% or less
with no nocturial hypoglycemia
 Safety measures were the proportion of patients with
hypoglycemia events & frequency of hypoglycemic
events

25. Demographics & Baseline Characteristics of
the Study Population
Characteristics Insulin Lantus+
OAD
Premixed Insulin
Patient, n
Male/Female
Age, mean ± SD
Weight, kg, mean ± SD
BMI, mean ± SD
Duration of DM, years, mean ±
SD
Duration of OAD treatment,
years, mean ± SD
C-peptide, ng/mL, mean ± SD
A1C, mean ± SD
Fasting blood glucose, mean ±
SD
67
64/36
83.8±15.3
28.9±3.4
28.9±3.4
12.1± 6.7
8.9±5.9
3.5±2.0
8.84±1.06
165± 33
9.2±1.8
63
48/52
69.6±4.1
80.5 ±13.0
28.9 ±3.3
11.1 ± 7.6
6.9±5.2
3.8±2.7
8.89±0.91
171±39
9.5 ± 2.2

26. Results
Glycemic Control Blood glucose level
 Lantus + OAD
 A1C decreased from 8.8% to 7.0%
 Premixed insulin
 A1C decreased from 8.9% to 7.4%
 The mean adjusted decrease in
A1C was greater for Lantus +OAD
than for premixed (P=0.03)
 Overall, the proportion of
patients that reached the target
A1C level was significant higher
in patients receiving
Lantus+OAD (P=0.01)
 Glargine +OAD
 FBG decreased from 165
mg/dl to 111mg/dl
 Premixed insulin
 FBF decreased from 171
mg/dl to 129 mg/dl
 Decreases in mean
adjusted FBG levels were
significant greater with
Lantus + OAD than
premixed (P=0.02)

27. Rates of Confirmed Hypoglycemic Events per
Patient-Year
Type of
Hypoglycemia
Lantus+ Oral
Antidiabetic Agents
Premixed
Insulin
P-Value
All episodes of
hypoglycemia
(confirmed +
unconfirmed)
5.59 11.39 0.01
All episodes of
confirmed
hypoglycemia
3.68 9.09 0.008
Confirmed
symptomatic
hypoglycemia
2.22 5.01 0.06
Confirmed nocturnal 0.39 0.71 0.26

28. Weight gain & Adverse Events
 Mean weight gain
 Glargine + OAD: 1.3 ± 3 kg
 Premixed insulin: 2.2 ± 3.9 kg
 P value = 0.17
 Adverse Events
 Similar between two groups
 Most common AE
 Respiratory, nervous system & GI disorders
 Withdraw from the study due AE
 Lantus+ OAD: 1 patient
 Premixed insulin:2 patient

29. Discussion
 The results presented
 Patients aged 65 & older with type II DM poorly
controlled on oral therapy, adding a single
injection of Lantusto glimepiride & Metformin can
provide more effective glycemic control than stop
OAD & starting BID 70/30
 Lantus + OAD regimen enabled 55% of patients
to reach A1C of 7% or less without experiencing
nocturnal hypoglycemia

30. Some considerations
 Risk of comorbidities in elderly patients
 The possibility that patients developed
contraindications to OADs over time
 Individual assessment with tailored therapy is
still important
 Must consider the compromise between
achieving tight glycemic control & limiting the
risk of hypoglycemia in this patient populations

31. Conclusion
 This study demonstrated that, for elderly
patients with type II DM who are inadequately
controlled with Metformin + a sulfonylurea,
adding a Once daily injection of Lantus is a
simple method that is more effective in
improving glycemic control & less likely to cause
hypoglycemia than starting BID injection of
premixed insulin without oral agents

32. Oral Antidiabetic Medications
Drugs Drugs Mechanism of
Action
Comments
Glyburide
Glipizide
Glimipiride
Sulfonylurea
s
Increase insulin
secretion
-Start low dose in
elderly, renal
adjustmnent
- Most SE:
hypoglycemia, N/V &
skin reactions
Prandin
Starlix
Meglitinides Stimulate insulin
secretion
Rapid absorption, short
duration of action, dose
with meals
Precose
Glyset
Alpha-
glucosidase
Inhibitors
Delay glucose
absorption,
decrease rate of
carbohydrate
No renal adjustment
Contraindication:
-Cirrhosis (Precose)
-Colon ulceration

33. Oral Antidiabetic Medications
Drugs Drug class Mechanism of Action Comments
Metformin Biguanides - Increase insulin
sensitivity;
-Decrease insulin
resistance
- Decrease
glucogenesis
-Weight reduction
- Lipid improvement
(↑ TG & ↓LDL)
-Contraindication:
SCr(males) ≥1.5 &
(female)≥ 1.4
Actos
Avandia
Thiazolidinediones
(TZD)
Insulin sensitizers -Good for fasting
sugar & no renal
adjustment
- SE: Increase LFT,
edema, weight gain
-Actos: Risk for
bladder cancer
Januvia
Onglyza
Tradjenta
DPP4 Inhibitors -Increase insulin
synthesis & secretion
-Decrease glucagon
-Delay gastric
emptying , promotes b-
-Safe SE profile
- Onglyza: drug
interaction with
CYP3A4

34. Insulin Type of
Insulin
Onset Role in blood glucose
management
Humalog
Novolog
Apidra
Rapid acting 15 to 30
minutes
-Cover insulin needs
before or immediately
after meals
- Used with long acting
insulin
Novolin R
Humulin R
Short acting 30 minutes to 1
hour
- Given 30 to 60 minutes
before meals
Lantus
Levemir
Long acting 30 minutes to 3
hours
-Cover insulin needs for
one full day
Humalog mix
Novolog mix
Pre-mixed 30 minutes -A combination of specific
proportions of
intermediate-acting &
short acting insulin
-Give twice daily before
meals

35. GLP-1 Effects in Human
 Drug class: Glucagon-Like Peptide Receptor
Agonist
 Therapeutic benefits:
 Enhance glucose dependent insulin secretion
 Promote satiety & reduces appetite
 Decreases post meal glucagon secretion
 Delays gastric emptying
 Available:
 Byetta ®
 Victoza®

36. Summary
 Management of diabetes is a life-long
commitment
 Management of diabetes includes diet, exercise
and drugs
 Regular physician
 Considerations when developing or
recommending drug therapy plan
 Efficacy therapy
 Safety of therapy
 Impact on compliance
 Financial burden