Memorias Conferencia Científica Anual sobre Síndrome Metabólico 2017 - Programa Científico
Manejo de la diabetes en el anciano
Dr. Guillermo E. Umpierrez
Professor of Medicine in the Division of Endocrinology at Emory University School of Medicine, Section Head, Diabetes and Endocrinology. USA. Editor en Jefe del BJM Open Diabetes Research and Care.
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Maintaining Glycemic Control in Older Adults with Diabetes
1. Guillermo Umpierrez, MD, CDE. FACE,Guillermo Umpierrez, MD, CDE. FACE,
FACPFACP
Professor of MedicineProfessor of Medicine
Division of EndocrinologyDivision of Endocrinology
Emory University SOMEmory University SOM
Atlanta, Georgia, USAAtlanta, Georgia, USA
Manejo de la Diabetes en elManejo de la Diabetes en el
AncianoAnciano
2. External Industry
Relationships *
Company Name(s) Role
Equity, stock, or
options in biomedical
industry companies or
publishers
BMJ Open Diabetes
Research & Care
AACE
Editor-in-Chief
Board of Directors
Industry funds to
Emory University for
my research
Merck,
Sanofi,
Novo Nordisk
Boehringer Ingelhein
Astra Zeneca
Investigator-Initiated
Research Projects
Industry
Advisory/Consultant
activities
Dr. Guillermo Umpierrez,
Personal/Professional Financial Relationships with Industry
February 2017
3. Educational ObjectivesEducational Objectives
1. Scope of the problem and burden of1. Scope of the problem and burden of
complications in the elderly populationcomplications in the elderly population
2. Importance of adequate and individualized2. Importance of adequate and individualized
glucose control in this populationglucose control in this population
Recent guideline recommendationsRecent guideline recommendations
3. Methods for achieving glucose control in3. Methods for achieving glucose control in
elderly patientselderly patients
4. Definition of theDefinition of the “Elderly” Patient?“Elderly” Patient?
No general agreement on the age atNo general agreement on the age at
which a person becomes elderlywhich a person becomes elderly
Most developed countries: ≥65 yoMost developed countries: ≥65 yo
Medicare eligibility: ≥ 65 yoMedicare eligibility: ≥ 65 yo
United Nations: ≥ 60 yoUnited Nations: ≥ 60 yo
WHO study in Africa: ≥ 50 yoWHO study in Africa: ≥ 50 yo
http://www.who.int/healthinfo/survey/ageingdefnolder/en/; National Institute of Aging: Minimum Data Set
Project Directory of Research on Adult Health and Ageing in Africa: 1995-2003;.
Speaker definition: age= 10 years older than the eldest
in this room
5. Exponential Growth of Adults ≥ 65 in the USExponential Growth of Adults ≥ 65 in the US
www.aoa.gov/Aging_Statistics/future_growth/future_growth.aspx#age
www.cdc.gov/diabetes/statistics/incidence/fig5.htm.
1 out of every 5
•“By 2030, it is estimated that there will be 8.3 billion people on this planet, with 13% over the age
of 65 years—the fastest-growing age group”
6. Global Population Increase of PeopleGlobal Population Increase of People
Aged ≥ 65 years: 1950-2050Aged ≥ 65 years: 1950-2050
Source: United Nations. World Population Prospects: The 2010 Revision.
7. People are Living LongerPeople are Living Longer
US Population of Adults 55+,
(Millions)
Between 2010-2028, 8000 baby
boomers will turn 65+
CDC 2010 data; http://www.aarp.org/personal-growth/transitions/boomers_65
Average Life Expectancy
76.5
9. Age at Diagnosis of Incident Cases ofAge at Diagnosis of Incident Cases of
Diabetes, Aged 18–79 Years, US, 2011Diabetes, Aged 18–79 Years, US, 2011
Data Source: Centers for Disease Control and Prevention (CDC), National Center for Health Statistics,
Division of Health Interview Statistics, data from the National Health Interview Survey, 2011.
27%
21%
10. Prevalent Comormidities among
older patients with T2DM
% of population with
specific comorbidities
Nielfeld MR Diabetes Care; 2003; 26:1344-1349
11. DM in the Elderly: Outpatient ManagementDM in the Elderly: Outpatient Management
ADA & AGS Consensus . JAGS 2012: 1-15
Diab Care,36: Suppl 1, 2013:S11-S-66
Garber et al. Endocrine Practice, in press 2013
12. Goals of DM managementGoals of DM management
Control hyperglycemiaControl hyperglycemia
Avoidance of hypoglycemiaAvoidance of hypoglycemia
Prevent, manage, and treatPrevent, manage, and treat
macrovascular and microvascularmacrovascular and microvascular
complicationscomplications
Maintain or improve overall healthMaintain or improve overall health
statusstatus
14. Common Issues Affecting Older PatientsCommon Issues Affecting Older Patients
Increased comorbiditiesIncreased comorbidities
High burden of CKD and CVDHigh burden of CKD and CVD
~25-30 % of those > 85yo have dementia~25-30 % of those > 85yo have dementia
Decreasing visionDecreasing vision
Poor dentition and decreased appetitePoor dentition and decreased appetite
PolypharmacyPolypharmacy
Limited physical activity/disabilityLimited physical activity/disability
Limited financial resourcesLimited financial resources
15. 2003/2013 AGS Guidelines for the Older2003/2013 AGS Guidelines for the Older
Person with Diabetes MellitusPerson with Diabetes Mellitus
Focus on individualizing care and educationFocus on individualizing care and education
Prevention and management of cardiovascularPrevention and management of cardiovascular
risk factorsrisk factors
Prevention and management of microvascularPrevention and management of microvascular
complications via glycemic controlcomplications via glycemic control
Screen for and treat geriatric syndromes thatScreen for and treat geriatric syndromes that
are more common in older adults with DMare more common in older adults with DM
CHF/American Geriatrics Society (AGS) Panel . Guidelines for Improving the Care of the Older
Person with Diabetes Mellitus. J Am Geri Soc 2003; 51:S265-S280
16. American Geriatric Society:American Geriatric Society:
A1c Recommendations 2013 for 65+A1c Recommendations 2013 for 65+
7.5 - 8%7.5 - 8% in general for the older adultsin general for the older adults
7% - 7.5%7% - 7.5% may be appropriate if it can be safelymay be appropriate if it can be safely
achieved in healthy older adults with fewachieved in healthy older adults with few
comorbidities and good functional statuscomorbidities and good functional status
8% - 9%8% - 9% is appropriate for older adults withis appropriate for older adults with
multiple comorbidities, poor health, and limitedmultiple comorbidities, poor health, and limited
life expectancy (IIA)life expectancy (IIA)
Potential harm in lowering A1C to < 6.5% in olderPotential harm in lowering A1C to < 6.5% in older
adults with type 2 DM (IIA)adults with type 2 DM (IIA)
CHF/American Geriatrics Society (AGS) Panel . Guidelines for Improving the Care of the Older
Person with Diabetes Mellitus. J Am Geri Soc 2013; 51:S265-S280
17. ADA, Glycemic Targets in Older AdultsADA, Glycemic Targets in Older Adults
Standards of care. Older adults. ADA.Standards of care. Older adults. ADA. Diabetes CareDiabetes Care. 2016;(suppl 1):S83.. 2016;(suppl 1):S83.
Target Rationale Fasting Bedtime
Blood
Pressure
Lipids
A1C
< 7.5%
Longer remaining
life expectancy
90-130 90-150 <140/90
Statin unless
contraindicated
or not tolerated
A1C
< 8%
Intermediate
remaining life
expectancy, high
treatment burden,
hypoglycemia,
vulnerability, fall risk
90-150 100-180 <140/90
Statin unless
contraindicated
or not tolerated
A1C
<8.5%
Limited remaining
life expectancy
makes benefit
uncertain
100-180 110-200 <150/90
Consider
likelihood of
benefit with
statin (secondary
prevention more
so than primary)
18. N = 652,378 patients receiving insulin or sulfonylurea. The denominator population: patients 75
years or older; serum creatinine level, 2.0mg/dL; or diagnosis of cognitive impairment or
dementia. A,B,C, outliers.
Tseng CL, et al. JAMA Intern Med. 2014;174:259-268.
http://www.va.gov/health/NewsFeatures/20111115a.asp.
Diabetes May Be Over-treatedDiabetes May Be Over-treated
Among Older AdultsAmong Older Adults
• About 25% of patients in the VA system have diabetes
VA Healthcare System
6.5 - 7
6.0 - <6.5
<6
19. Longitudinal Trends in Hospital Admission for
Hyperglycemia and Hypoglycemia in Older Adults
Hypoglycemia Hyperglycemia
Lipska KJ, et al. JAMA Intern Med.
2014;174:1116-1124.
• Currently, hypoglycemia accounts for more hospital admissions than hyperglycemia
• Hypoglycemia risk is greatest in patients aged ≥ 75 years
0
50
100
150
200
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
HospitalAdmissions
per1000,000person-years
Year
65-74 y 75-84 y ≥ 85 y
0
50
100
150
200
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
HospitalAdmissions
per1000,000person-years
Year
65-74 y 75-84 y ≥ 85 y
20. Lifestyle changes
Maintenance of Glycemic Control with OralMaintenance of Glycemic Control with Oral
Antidiabetic Agents in Elderly PopulationsAntidiabetic Agents in Elderly Populations
Metformin DPP4-I
SGLT2-I GLP1-
RAAcarbose
Avoid/Caution:
1.Sulfonylures due to hypoglycemia, CVD?
2.TZDs due to risk of osteoporosis, fractures and
HF
21. Efficacy of metformin in elderly and old-elderly
(>75 yrs) vs. non-elderly (<65 yrs) patients.
Data are mean SEM.
*P < 0.05;
**P < 0.01;
***P < 0.001 vs. baseline.
Metformin in elderly
patients with T2D is
not different from
that in non-elderly
patients,
Ito et al. Geriatr Gerontol Int 2011; 11: 55–62
22. SulfonylureasSulfonylureas
Used by 30-45% of type 2 diabeticsUsed by 30-45% of type 2 diabetics
Those with longer half-life have increased risk ofThose with longer half-life have increased risk of
hypoglycemiahypoglycemia
• GlyburideGlyburide
Risk factors of hypoglycemia with sulfonylureasRisk factors of hypoglycemia with sulfonylureas
• Age > 60, disability, poor nutrition, polypharmacyAge > 60, disability, poor nutrition, polypharmacy
• Drugs which potentiate their actionDrugs which potentiate their action
23. Relative Risk for experiencing hypoglycemia:Relative Risk for experiencing hypoglycemia:
Glyburide vs other secretagoguesGlyburide vs other secretagogues
Glyburide was associated with a 52% greater risk of experiencing at least one episode
of hypoglycemia compared with other secretagogues (RR 1.52 [95% CI 1.21–1.92]) and
with 83% greater risk compared with other sulfonylureas (1.83 [1.35–2.49]).
Gangji et al Diabetes Care 30:389–394, 2007
24. Hypoglycemia and Annualized Mortality
Rates Within Treatment Groups: ACCORD
None
>1
0
1
2
3
4
5
Standard
Intensive
1.0 1.3
4.9
2.9
Percent(%)perYear
Requiring Medical Assistance
(HMA)‡
None
≥1
0
1
2
3
4
5
Standard
Intensive
1.0 1.2
3.7
2.8
Percent(%)perYear
Requiring Any Assistance, Medical
orNon-medical (HA)†
Adapted from: Bonds DE, et al. BMJ. 2010 Jan 8;340:b4909. doi: 10.1136/ bmj.b4909.
n=201/
16315*
n=53/
1924*
n=176/
17297*
n=21/
564*
n=220/
17031*
n=34/
1208*
n=180/
17516*
n=17/
345*
Mortality Rate (n=451 deaths)
* Person-years
† p = .076 forinteraction between history of hypoglycemia requiring any assistance and glycemia intervention
‡ p = .009 forinteraction between history of hypoglycemia requiring medical assistance and glycemia intervention
25. Severe Hypoglycemia in 3 Outcome Trials of
Intensive Glucose Control in Type 2 Diabetes
0
5
10
15
20
25
VADT ACCORD ADVANCE
%Patientswithatleastonesevere
hypoglycemiceventduringthetrial Intensive Control
Standard Control
p < .001
p < .001
p < .001
Adapted from:
1. The Action to Control CardiovascularRisk in Diabetes Study Group. N EnglJMed. 2008;358:2545-2559.
2. The ADVANCECollaborative Group. N EnglJMed. 2008;358:2560-2572.
3. Duckworth W, et al.. N EnglJMed. 2009;360:129-139.
26. All-Cause Mortality following Treatment with
Metformin or Glyburide in Patients with T2D
Glyburide
Metformin
Reza et al. Arch Iranian Medi, 20 (3):141-146, 2017 141
717 patients with T2D (271 on glyburide, 446 on
metformin monotherapy, 3 year F/U.
All cause mortality 6.3% in glyburide and 1.6% in
metfomin group, p<0.001
27. CGM Can Reveal Unsuspected Hypo- and Hyperglycemia
in Well-Controlled Older Adults With T2DM
• Study participants
! N = 25
! SU ± MET, no insulin
! Age: 73.9 ± 4.4 y
! Duration of DM: 11 ± 7 y
! Baseline A1C: 6.2 ± 0.8%
! FPG: 139 ± 40 mg/dL
• Hypoglycemia
! Overall, 20 of 25 patients
had hypoglycemia
! 14 of 25 had BG ≤ 40 mg/dL
! NONE of the patients
reported hypoglycemia
Hay LC, et al. Diabetes Technol Ther. 2003;5:19-26.
Designnote:Scalewillbeconvertedtomg/dLif
selectedforpresentation
Typical 24-h CGM Tracing
28. Placebo-corrected change from baseline in HbA1c - Monotherapy
Comparative Efficacies of DPP-4sComparative Efficacies of DPP-4s
-0.1
-0.3
-0.2
-0.4
-0.8
-0.5
-0.6
-0.7
-0.9
-1.0
-1.1
-1.2
ΔHbA1c(%) Alogliptin1
12.5mg 25mg
7.9% 7.9%
Linagliptin2
5mg 5mg
8.1% 8.0%
Saxagliptin2
5mg 5mg
7-10% 8.0%
Sitagliptin2
100mg 100mg
8.0% 8.0%
Vildagliptin3
50mg BID 50mg
8.6% 8.4%
The current DPP-4s have comparative efficacy
1. DeFronzo R, et al. Diabetes Care 2008;31:2315-2317.
2. Linagliptin Prescribing Information.
3. Saxagliptin Prescribing Information.
4. Sitagliptin Prescribing Information.
5. Vildagliptin Summary of Product Characteristics.
-0.56
-0.59 -0.6
-0.7
-0.4
-0.6 -0.6
-0.8
-0.5
-0.7
29. Saxagliptin compared with GlimepirideSaxagliptin compared with Glimepiride
in elderly patients with type 2 diabetesin elderly patients with type 2 diabetes
Schernthaner et al. Diabetes, Obesity and Metabolism 17: 630–638, 2015
30. Linagliptin Shows Rates of HypoglycemiaLinagliptin Shows Rates of Hypoglycemia
Similar to PlaceboSimilar to Placebo
Yki-Järvinen H, et al. Diabetes Care. 2013;36:3875-3881.
Investigator-defined hypoglycemia AEs at week 24 by category
31. The durability of sitagliptin in elderlyThe durability of sitagliptin in elderly
patients with T2Dpatients with T2D
Ching-Jung Hsieh et al. Clin Interv Aging. 2014; 9: 1905–1911
32. Benefits and Advantages of DPP4-iBenefits and Advantages of DPP4-i
Therapy in Elderly Patients with T2DTherapy in Elderly Patients with T2D
Lower HbA1c ~0.4%–0.9% from baselineLower HbA1c ~0.4%–0.9% from baseline
Weight neutralWeight neutral
Once-daily oral therapyOnce-daily oral therapy
Low-risk of hypoglycemia (as monotherapy)Low-risk of hypoglycemia (as monotherapy)
Minimal GI side effectsMinimal GI side effects
Approved as monotherapy or combinationApproved as monotherapy or combination
therapytherapy
33. Thiazolidinediones:Thiazolidinediones:
Rosiglitazone - PioglitazoneRosiglitazone - Pioglitazone
Mechanism of action: Enhance tissue response
to insulin; decrease
hepatic glucose production
Therapeutic efficacy: Decrease HbA1c 0.8% - 2.6%
Recommended dosing: Pioglitazone: 15-45 mg QD
Side effects: Edema, weight gain, CHF, MI
osteopenia, bladder cancer?
Contraindications: Known hypersensitivity; pre-
existing liver disease, type 1
diabetes, DKA
35. Perspectives on SGLT2 InhibitionPerspectives on SGLT2 Inhibition
AdvantagesAdvantages
Improved glycemicImproved glycemic
controlcontrol
Weight lossWeight loss
Low risk ofLow risk of
hypoglycemiahypoglycemia
Blood pressureBlood pressure
loweringlowering
Reduce cardiovascularReduce cardiovascular
events and mortalityevents and mortality
Concerns
• Polyuria
• Electrolyte
disturbances
• Urinary tract infections
• Fungal genital
infections
• DKA
• Bone fractures
36. Older Adults and Insulin TherapyOlder Adults and Insulin Therapy
The increased risk of hypoglycemia due toThe increased risk of hypoglycemia due to
antidiabetic agents is a major concern whenantidiabetic agents is a major concern when
considering treatment options in older adultsconsidering treatment options in older adults
Insulin is the antidiabetic agent most oftenInsulin is the antidiabetic agent most often
responsible for hypoglycemiaresponsible for hypoglycemia
Characteristics Desired in Insulin RegimensCharacteristics Desired in Insulin Regimens
Lower risk of hypoglycemiaLower risk of hypoglycemia
Once daily dosingOnce daily dosing
Easy to administerEasy to administer
Budnitz DS, et al. N Engl J Med. 2011;365:2002-2012.
37. Older Adults Have the Highest Risk ofOlder Adults Have the Highest Risk of
Insulin-Related Hypoglycemia andInsulin-Related Hypoglycemia and
Errors Leading to ED VisitsErrors Leading to ED Visits
National estimate of 97,648 insulin-related hypoglycemia and insulin errors derived from
8100 cases reported in CDC databases during 2007-2011.
1. Geller AI, et al. JAMA Intern Med. 2014;174:678-686.
2. Budnitz DS, et al. N Engl J Med. 2011;365:2002-2012.
Patients aged ≥ 80 years have the highest risk of ED visits forPatients aged ≥ 80 years have the highest risk of ED visits for
hypoglycemiahypoglycemia11
94.6% of hospitalizations related to antihyperglycemic agents in94.6% of hospitalizations related to antihyperglycemic agents in
older adults are for hypoglycemiaolder adults are for hypoglycemia22
38. STEP IT UP A Bit (Pens vs Needles)STEP IT UP A Bit (Pens vs Needles)
Study TypeStudy Type:: Prospective, randomized,Prospective, randomized,
cross-over trialcross-over trial
Aim:Aim: Compare efficacy, patient satisfaction,Compare efficacy, patient satisfaction,
and safety of an add-on basal insulin viaand safety of an add-on basal insulin via
insulin pen vs by vial/syringe in elderly withinsulin pen vs by vial/syringe in elderly with
diabetes.diabetes.
Study SiteStudy Site: Grady Memorial Hospital: Grady Memorial Hospital
Patient PopulationPatient Population : 56 subjects ≥60 years: 56 subjects ≥60 years
old on diet ± OADs w/ A1c >7%old on diet ± OADs w/ A1c >7%
Newton, Ivie, Smiley, et al. ADA Scientific Sessions 2013, Abstract Poster 804; NCT 01240200
39. Effects of Pens vs Syringes on GlycemicEffects of Pens vs Syringes on Glycemic
ControlControl
Newton, Ivie, Smiley, et al. ADA Scientific Sessions 2013, Abstract Poster 804
Insulin initiation improves glycemic control in older adults
40. Insulin Pens Are Associated With Lower Risks of DosingInsulin Pens Are Associated With Lower Risks of Dosing
Errors and Hypoglycemia Than Vial-and-Syringe InsulinErrors and Hypoglycemia Than Vial-and-Syringe Insulin
DeliveryDelivery
Dosing Errors vs Delivery DeviceDosing Errors vs Delivery Device11
Hypoglycemia vs Delivery DeviceHypoglycemia vs Delivery Device11
Hypoglycemia, BG < 70 mg/dL; a
Events measured per person.
1. Newton C, et al. AACE Annual Meeting. 2013 [abstract 271].
2. Budnitz DS, et al. N Engl J Med. 2011;365:2002-2012.
• Insulin is implicated in 67% of all adverse drug event–related hospitalizations in older
adults2
• With vials and syringes, dosing errors are more common and lead to more hypoglycemic
events (1.5 vs 0.4 events, P = .01)1,a
• With pens, dosing errors did not significantly increase hypoglycemic events 1,a
P < .01
P < .05
41. And what about insulin in the nursingAnd what about insulin in the nursing
home setting?home setting?
More and more people with diabetes areMore and more people with diabetes are
living to older agesliving to older ages
Approximately 1 in 4 NH residents hasApproximately 1 in 4 NH residents has
diabetes (24-35%)diabetes (24-35%)
2007 study showed that only 38% met BG2007 study showed that only 38% met BG
goals and 67% reached A1c goals while in agoals and 67% reached A1c goals while in a
long-term care (LTC) facilitieslong-term care (LTC) facilities
Few studies have reported on the quality ofFew studies have reported on the quality of
DM care and glycemic control adjusted forDM care and glycemic control adjusted for
medication use in a LTCmedication use in a LTC
Travis S, etal. 2004 J Am Med Dir Assoc 5:320-327; Holt, et al. Diabetes Care 30:1454–1458, 2007
42. Prevalence of Diabetes andPrevalence of Diabetes and
Glycemic Control in Long-Term CareGlycemic Control in Long-Term Care
ResidentsResidents
Newton et al. JAMDA 14 (2013) 842e846
NPH
Premixed
16%
No Drug Rx
10%
SSI
25%
Basal
+/- SSI
24%
OAD
+/- SSI
43. Pasquel et al. BMJ Open Diabetes Research and Care 2015
Diabetes in long-term care facilitiesDiabetes in long-term care facilities
44. Diabetes Care in Elderly PatientsDiabetes Care in Elderly Patients
Admitted to Long-Term Care FacilitiesAdmitted to Long-Term Care Facilities
Study TypeStudy Type:: Pilot, RCT trialPilot, RCT trial
Aim:Aim: Determine differences in glycemic control withDetermine differences in glycemic control with
Basal insulin vs versus oral antidiabetic agents inBasal insulin vs versus oral antidiabetic agents in
nursing home patients with type 2 diabetesnursing home patients with type 2 diabetes
Patient PopulationPatient Population : 150 diabetic subjects treated: 150 diabetic subjects treated
with diet and/or OADs with BG >180 mg/dl or A1Cwith diet and/or OADs with BG >180 mg/dl or A1C
>7.5%>7.5%
Pasquel et al. BMJ Open Diabetes Research and Care 2015
45. Mean daily glucose levels in patients withMean daily glucose levels in patients with
T2D treated with basal insulin and oralT2D treated with basal insulin and oral
agents in long-term care facilitiesagents in long-term care facilities
Pasquel et al, BMJ Diabetes Care & Research 2015
46. Frequency in hypoglycemia in nursing home
patients treated with basal insulin or OADs
Pasquel et al, BMJ Diabetes Care & Research 2015
47. Randomized Controlled StudyRandomized Controlled Study
Comparing Linagliptin (± Metformin) andComparing Linagliptin (± Metformin) and
Glargine (± Metformin) in elderly patientsGlargine (± Metformin) in elderly patients
in LTCin LTC
Aim:Aim: Differences in glycemic control with BasalDifferences in glycemic control with Basal
(glargine) insulin(glargine) insulin (± Metformin)(± Metformin) vs linagliptinvs linagliptin (±(±
Metformin)Metformin) in nursing home patients with diabetesin nursing home patients with diabetes
Study SitesStudy Sites: Emory, Grady and AtlantaVAMC: Emory, Grady and AtlantaVAMC
Affiliated LTC facilitiesAffiliated LTC facilities
Patient PopulationPatient Population:T2D treated with diet and/or:T2D treated with diet and/or
OADs or Low-dose insulin (TDD < 0.1 U/Kg) withOADs or Low-dose insulin (TDD < 0.1 U/Kg) with
BG >180 mg/dl and/or A1C >7.5%BG >180 mg/dl and/or A1C >7.5%
Umpierrez et al, NCT01131052
48. Linagliptin versus Glargine in LTC
LTC residents with DM2
on diet, OADs, low-dose insulin
BG > 180 mg/dL and A1C > 7.5%
Glargine
(± metformin)
n= 75
Linagliptin
(± metformin)
n= 75
Umpierrez et al. ADA Scientific Meeting, San Diego, 2017
49. Glargine vs. Linagliptin in LTC:Glargine vs. Linagliptin in LTC:
Mean Weekly BG During TreatmentMean Weekly BG During Treatment
Basal Linagliptin p
Mean daily BG, mg/dL 157±36 146±34 0.06
Umpierrez et al. ADA Scientific Meeting, San Diego, 2017
50. BG <70 BG <54 BG <40
0
10
20
30
40
Frequency of Hypoglycemia According to Treatment GroupHypoglycemia(%)
Glargine Linagliptin
p<0.001
p=0.06
p=0.5
Glargine vs. Linagliptin in LTC:Glargine vs. Linagliptin in LTC:
Mean Weekly BG During TreatmentMean Weekly BG During Treatment
Umpierrez et al. ADA Scientific Meeting, San Diego, 2017
51. Treatment with linagliptin resulted in equivalent
glycemic control and in lower rates of hypoglycemia
compared to insulin glargine.
Our results indicate that an initial treatment with
linagliptin (± metformin) should be preferred over the
use of basal insulin (± metformin) in LTC residents
with T2D.
The use of antidiabetic agents associated with low-
rate of hypoglycemia should be preferred over agents
associated with hypoglycemia (insulin and insulin
secretagogues).
Linagliptin (± Metformin) and Glargine (± Metformin) inLinagliptin (± Metformin) and Glargine (± Metformin) in
LTC: Summary & ConclusionLTC: Summary & Conclusion
52. Management of Hyperglycemia in Type 2Management of Hyperglycemia in Type 2
Diabetes: A Patient-Centered ApproachDiabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) andPosition Statement of the American Diabetes Association (ADA) and
the European Association for the Study of Diabetes (EASD)the European Association for the Study of Diabetes (EASD)
Diabetes Care 2012;35:1364–1379
Diabetologia 2012;55:1577–1596
SUSU TZD SGLT2 GLP1DPP4 Insulin
53. Glycemic Treatment Goals in Elderly Subjects withGlycemic Treatment Goals in Elderly Subjects with
Diabetes.Diabetes. SummarySummary
Patients ≥ 65 years of age represent the largest growingPatients ≥ 65 years of age represent the largest growing
population with diabetespopulation with diabetes
The life expectancy is projected to increase and thisThe life expectancy is projected to increase and this
population is at greater risk of having diabeticpopulation is at greater risk of having diabetic
complicationscomplications
Individualize glycemic targets and educateIndividualize glycemic targets and educate
Target A1C < 7% for the healthier, older patientTarget A1C < 7% for the healthier, older patient
Target 7-8 for the older patient with multipleTarget 7-8 for the older patient with multiple
comorbidities, poor health,comorbidities, poor health, ↑↑ risk of hypoglycemia andrisk of hypoglycemia and
limited life expectancylimited life expectancy
More research is needed! Safest and most effectiveMore research is needed! Safest and most effective
regimen?regimen?
54. Glycemic Targets in Older Adults, ADAGlycemic Targets in Older Adults, ADA
Standards of care. Older adults. ADA.Standards of care. Older adults. ADA. Diabetes CareDiabetes Care. 2016;(suppl 1):S83.. 2016;(suppl 1):S83.
Target Rationale Fasting Bedtime
Blood
Pressure
Lipids
A1C
< 7.5%
Longer remaining
life expectancy
90-130 90-150 <140/90
Statin unless
contraindicated
or not tolerated
A1C
< 8%
Intermediate
remaining life
expectancy, high
treatment burden,
hypoglycemia,
vulnerability, fall risk
90-150 100-180 <140/90
Statin unless
contraindicated
or not tolerated
A1C
<8.5%
Limited remaining
life expectancy
makes benefit
uncertain
100-180 110-200 <150/90
Consider
likelihood of
benefit with
statin (secondary
prevention more
so than primary)
55. Patient Preference ORAL Agents in thePatient Preference ORAL Agents in the
Elderly: Hypoglycemia AvoidanceElderly: Hypoglycemia Avoidance
metformin
DPP4
inhibitor
TZD
α
-glucosidase
inhibitor
sulfonylurea
glinide
GLP1
Analogs
Insulin
SGLT2-I
Preferred Not PreferredCaution
56. ConclusionsConclusions
Individualize treatment regimenIndividualize treatment regimen
State appropriate glycemic goalsState appropriate glycemic goals
Treat cardiovascular risksTreat cardiovascular risks
Reduce medicationsReduce medications
Reduce fall riskReduce fall risk
Education and supportEducation and support
Watch for associated conditionsWatch for associated conditions
Depression, urinary incontinence, painDepression, urinary incontinence, pain
57. Guillermo E. Umpierrez, MDGuillermo E. Umpierrez, MD
geumpie@emory.edugeumpie@emory.edu
Thank you!Thank you!
58. Guillermo Umpierrez, MD, CDE. FACE,Guillermo Umpierrez, MD, CDE. FACE,
FACPFACP
Professor of MedicineProfessor of Medicine
Division of EndocrinologyDivision of Endocrinology
Emory University SOMEmory University SOM
Atlanta, Georgia, USAAtlanta, Georgia, USA
Management of Elderly SubjectsManagement of Elderly Subjects
with Diabeteswith Diabetes
Editor's Notes
Thank you Dr. Phillips for the introduction. I would also like to thank the ADA planning committee, members and guests for allowing me the opportunity to discuss the growing epidemic of diabetes in the older adult patient
(So we this outlines our educational course that we will take as I attempt to peel back a few layers of
And we all cringe at this word as each day we all get a little older. And we all know that the definitions can range.
So you can imagine why there is so much debate over this population
The WHO takes a slightly different approach by not only considering seniority but also cultural standards in certain countires
The Minimum Data Set Project consisted of: Directory of Research on Adult Health and Ageing in Africa: 1995-2003;Minimum Data Set (MDS) Version 1.0; and,Study on Global Ageing and Adult Health.
Take a closer look at the slope of thois graph because it looks eerily like
US Administration on Aging. Chart of Population 65 and over by age: 1900 to 2050. http://www.aoa.gov/Aging_Statistics/future_growth/future_growth.aspx#age
File: By_Age_65_and_over.xls Accessed May 26, 2013. (RW#9711; .xls on file)
Between 2010 and 2050, the United States is projected to experience rapid growth in its older population.2 In 2050, the number of Americans aged 65 and older is projected to be 88.5 million, more than double its projected population of 40.2 million in 2010. The baby boomers are largely responsible for this increase in the older population, as they will begin crossing into this category in 2011.3
Between 2010 and 2050, the U.S. population is projected to grow from 310 million to 439 million, an increase of 42 percent. The population is also expected to become much older, with nearly one in five U.S. residents aged 65 and older in 2030.
Why increase risk: Strong genetic predisposition
Age-related changes in carbohydrate metabolism
Altered glucose-induced insulin release
Resistance to insulin-mediated glucose disposal
Obese, inactive patients are more likely to develop diabetes as they age
This is not just a US phenomenon, but a global trend. This graph shows the global increase in the number of patients &gt;65 since 1950…and if you extrapolate the data to 2050 this equates into 188% increase in the number of patients &gt; 65
Additionally, this shift in the population is occurring globally and thus, we must increasingly be familiar with the special considerations for glycemic control in this population
A baby boomer is a person who was born during the demographic Post–World War II baby boom between the years 1946 and 1964, according to the U.S. Census Bureau.[1] The term &quot;baby boomer&quot; is also used in a cultural context.
This shows the distribution and you can see that patients ages 50-64 represent more than 25% of the population
In 2011, 63% of the adult (aged 18–79 years) incident cases of diabetes (i.e., cases diagnosed within the past year) were diagnosed between the ages of 40 and 64 years. About 16% were diagnosed at age 18–39 years, and about 21% were diagnosed at age 65–79 years
60–64 13.8 %; 65–69 9.5 %; 70–74 7.1 %; 75–79 4.7 %
From 1997 through 2011, the mean and median ages at diagnosis of diabetes among adults aged 18–79 years were very similar. In 2011, the mean and median age at diagnosis of diabetes was about 54
HT,Lipid disorders and CAD were among the 3 highest prevalent comorbidities.
We will see the majority of patients in the outpatient setting
The goals of diabetes care in older adults is similar to that of young patients. These are:
The care of older adults with diabets is complicated by their clinical and functcional heterogenetity
Also, do we have evidence that the same goals of therapy apply to the elderly population as to the young?
Recall that it takes an average of 8 years before benefits in reducing microvascular complications
2-3 years required to see benefits from blood pressure and lipid control
Less aggressive glycemic targets may be appropriate to prevent complications
Poor wound healing
Symptoms of hyperglycemia
Cognitive dysfunction
In summary, a reminder of the themes from the AGS guidelines, and hopefully we have generated some questions and interest.
Reference: California Healthcare Foundation/American Geriatrics Society (AGS) Panel on Improving Care of Elders with Diabetes. Guidelines for Improving the Care of the Older Person with Diabetes Mellitus. J Am Geriatri Soc 2003; 51:S265-S280.
the continued inclusion and emphasis of six relevant geriatric syndromes that when detected by primary care providers, assist with improving DM care. The syndromes were included in the original guideline because there
was population-based evidence that these syndromes were more prevalent in persons with DM
or, in the absence of clear prevalence estimates, there was a strong pathophysiological reason to
The syndromes are depression, polypharmacy, cognitive impairment, incontinence, falls, persistent pain
2003 recs:General Recommendations
1. For older persons, target hemoglobin A
1c
(A1C)
should be individualized. A reasonable goal for A1C
in relatively healthy adults with good functional status
is 7% or lower. For frail older adults, persons
with life expectancy of less than 5 years, and others
in whom the risks of intensive glycemic control appear
to outweigh the benefits, a less stringent target
such as 8% is appropriate. (IIIB)
Diabetes is associated with increased risk of multiple
coexisting medical conditions in older adults ranging from
CVD to cancer and potentially impacting treatment decisions,
such as whether stringent glycemic control would be
of net benefit.36,37 A 5-year longitudinal, observational
study of Italian patients with type 2 diabetes categorized
patients into subgroups of high (mean age 64.3 years [SD
9.5]) and low-to-moderate comorbidity (mean age
61.7 years [SD 10.5]) using a validated patient-reported
measure of comorbidity. Having an A1C of 6.5
or &lt;7% at baseline was associated with lower 5-year incidence
of cardiovascular events in the low-to-moderate
comorbidity subgroup, but not in the high comorbidity
subgroup, suggesting that patients with high levels of
comorbidity may not receive cardiovascular benefit from
intensive blood glucose control.38
FXCX:
AACE/ACE consensus statement: p543 c2 bullet2 under principles and p544 c1 under A1C goal
ADA/EASD consensus statement: A1C 7%: p194 c1 last para and p194 c1 para under glycemic goals
A1C 8%: ADA 2012 standards of care: p S19, col 1, 2nd bullet; outcomes from ACCORD, ADVANCE, VADT: pp S19-S21 [confirmed MT 1/20/2012]
Tseng CL, Soroka O, Maney M, Aron DC, Pogach LM. Assessing potential glycemic overtreatment in persons at hypoglycemic risk. JAMA Intern Med. 2014 Feb 1;174(2):259-68. doi: 10.1001/jamainternmed.2013.12963. PubMed PMID: 24322626.
editorial: Andrews MA, O&apos;Malley PG. Diabetes overtreatment in elderly individuals: risky business in need of better management. JAMA. 2014 Jun 11;311(22):2326-7. doi: 10.1001/jama.2014.4563. PubMed PMID: 24915264.
Fig 1, p 263 (permission needed)
Type 2 diabetes is a progressive disease marked by increasing insulin resistance and failure of the pancreatic beta cells to produce insulin. Therefore, treatment will need to be intensified as diabetes progresses.
If FBG has been reduced to target levels but HbA1c values remain high, basal insulin therapy can be intensified with the addition of one shot of prandial insulin.
This is known as the Basal-Plus approach. A rapid-acting prandial insulin, such as insulin glulisine, should be initiated once daily with the main meal of the day1.
Raccah D, et al. Diabetes Metab Res Rev 2007; 23: 257-64.
Hay LC, Wilmshurst EG, Fulcher G. Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the results of continuous glucose monitoring. Diabetes Technol Ther. 2003;5(1):19-26. PubMed PMID: 12725703.
Aims: To assess the efcacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control.
Methods: In this multinational, randomized, double-blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged ≥65 years were randomized (1 : 1) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day, added to metformin, during a 52-week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) &lt;7.0% at week 52 without conrmed/severe hypoglycaemia. The key secondary endpoint was incidence of conrmed/severe hypoglycaemia. Safety and tolerability were also assessed.
Results: Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% condence interval 0.73, 1.34; p = 0.9415); however, a signicant treatment-by-age interaction effect was detected (p = 0.0389): saxagliptin was numerically (but not signicantly) superior to glimepiride for patients aged &lt;75 years (39.2 vs 33.3%) and numerically inferior for patients aged ≥75 years (35.9 vs 45.5%). The incidence of conrmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal p &lt; 0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride.
Conclusion: As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with
T2D aged ≥65 years.
To evaluate the durability of sitagliptin and to assess changes in clinical chronic complications following sitagliptin monotherapy for 48 months in elderly patients with type 2 diabetes mellitus (T2DM).
Subjects and methods
We enrolled 76 drug-naïve patients (40 women and 36 men; mean age: 71.3±11.7 years) with T2DM who received 25–100 mg of sitagliptin therapy from an outpatient clinic. The observational period for each patient was &gt;48 months, beginning at the time sitagliptin therapy was initiated. The following were measured or performed at the beginning of each year: body mass index; serum total cholesterol, low-density lipoprotein, high-density lipoprotein; triglyceride levels; creatinine (Cr) levels; urine albumin and urine Cr; nonmydriatic fundusgraphy; and semiquantified neuropathy. The fasting plasma glucose and glycated hemoglobin (HbA1c) was measured every 3–6 months.
Results
The change in HbA1c was significantly reduced after 6 months of therapy (7.1%±0.8% to 6.3%±0.2%). No changes in fasting plasma glucose, Cr, serum total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, body mass index, and microvascular complications were apparent. Using repeated measures to test the sequential changes in HbA1c from month 6 to month 48, the test of within-subjects effect was not significant (P=0.34).
Conclusion
Sitagliptin has a durable effect and stabilizes microvascular complication progression in elderly patients. This study can provide useful data for clinicians and health care professionals using sitagliptin monotherapy in the treatment of elderly patients with T2DM.
In healthy individuals, the renal glomeruli filter approximately 180 g of glucose per day. Virtually all of the filtered glucose is reabsorbed in the proximal tubules through the sodium glucose cotransporters SGLT-2 and SGLT -1
SGLT2 inhibition — a novel strategy for diabetes treatment.
Genetic mutations in the kidney-specific SGLT2 isoform that result in benign renal glycosuria, as well as preclinical and clinical studies with SGLT2 inhibitors in type 2 diabetes, support the potential of this approach. These investigations indicate that elevating renal glucose excretion by suppressing SGLT2 can reduce plasma glucose levels, as well as decrease weight.
Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053. PubMed PMID: 22111719. (RW#8659; pdf on file)
FXCX:
Budnitz 2011: abstract
Hypo: table 3 p2007 AND p2010 c2 para1
insulin: 13.9% AND table 4 p2008 and fig 1 and p2006 c2 last para
Geller AI, Shehab N, Lovegrove MC, Kegler SR, Weidenbach KN, Ryan GJ, Budnitz DS. National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. JAMA Intern Med. 2014 Mar 10. [Epub ahead of print]. doi:10.1001/jamainternmed.2014.136.
Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053. PubMed PMID: 22111719.
FXCX:
Geller 2014: table 2 pE4 AND pE4 c1 para2 AND table 1 pE3
Budnitz 2011: p2006 c1 last para: should be 94.6% (MT: corrected)
--Based on an investigator-initiated proposal, we carried out….
-each of the medical centers has a large inner-city, urban population
Average age was 69 and average length of diabetes was 12 years, A1c 8.8 at baseline
A1c at 6 months, syringe group A1c was 7.6 and pen group was 8%
Newton C, Ivie E, Smiley D, Cardona S, Umpierrez G. High rates of insulin syringe self-dosing errors in the elderly despite normal vision and dexterity. AACE 22nd Annual Scientific & Clinical Congress. abstract 271. (RW#9715; pdf of abstract book on file)
http://am.aace.com/sites/all//files/2013_abstract_book_nocover.pdf (see pp 60-61).
FXCX:
Newton 2013: abstract
Budnitz 2011: p2006 c1 last para: 94.6% for hypo in elderly (MT: bullet removed from this slide)
Abstract AND p2006 c2 para2: 67% for 4 agents including insulin (MT: corrected)
And some retrospective studies suggest that &lt;50% actually get to a goal A1c &lt;7%
Diabetes Care in Long-Term Care Facilities: A Randomized Controlled Study
Management of hyperglycemia is challenging in geriatric patients admitted to long-term care (LTC) facilities. This pilot trial, randomized patients with T2D from two LTC facilities with hyperglycemia (BG &gt;180 mg/dl or two BG &gt;150 mg/dl and/or A1C &gt;7.5%) treated with diet and/or oral antidiabetic drugs (OAD), to receive basal (glargine, starting dose 0.1 U/kg/day) plus correction doses of glulisine before meals for BG &gt;200 mg/dl, n=46) or to continue OAD plus sliding scale regular insulin (SSI) before meals for BG &gt;200 mg/dl (n=54) for 26 weeks. Primary endpoints included differences in glycemic control as measured by mean fasting and daily BG, % of BG between 80-180 mg/dl, A1C levels, and hypoglycemia between groups.
A total of 100 patients (age: 79.1±8.2 yr, BMI: 29.7±6.7 kg/m2, female: 63%, acute rehab (n=90) and LTC (n=10) had a randomization BG of 167.5±45 mg/dl and admission A1C of 6.6±0.9% (Table). There were no differences in mean fasting BG, number of BG within target, or A1C levels at 3 and 6 months. The mean daily BG during the study; however, was higher in basal group compared to OAD plus SSI group. There were no differences in hypoglycemia, number of emergency room visits, need for hospitalizations or mortality between treatment groups.
In summary, these results indicate that most T2D patients in LTC facilities achieve and maintain good glycemic control without differences in A1C, fasting BG, BG within target and hypoglycemic events, when treated with basal insulin or OAD plus supplements.
VS
Diabetes Care in Long-Term Care Facilities: A Randomized Controlled Study
Management of hyperglycemia is challenging in geriatric patients admitted to long-term care (LTC) facilities. This pilot trial, randomized patients with T2D from two LTC facilities with hyperglycemia (BG &gt;180 mg/dl or two BG &gt;150 mg/dl and/or A1C &gt;7.5%) treated with diet and/or oral antidiabetic drugs (OAD), to receive basal (glargine, starting dose 0.1 U/kg/day) plus correction doses of glulisine before meals for BG &gt;200 mg/dl, n=46) or to continue OAD plus sliding scale regular insulin (SSI) before meals for BG &gt;200 mg/dl (n=54) for 26 weeks. Primary endpoints included differences in glycemic control as measured by mean fasting and daily BG, % of BG between 80-180 mg/dl, A1C levels, and hypoglycemia between groups.
A total of 100 patients (age: 79.1±8.2 yr, BMI: 29.7±6.7 kg/m2, female: 63%, acute rehab (n=90) and LTC (n=10) had a randomization BG of 167.5±45 mg/dl and admission A1C of 6.6±0.9% (Table). There were no differences in mean fasting BG, number of BG within target, or A1C levels at 3 and 6 months. The mean daily BG during the study; however, was higher in basal group compared to OAD plus SSI group. There were no differences in hypoglycemia, number of emergency room visits, need for hospitalizations or mortality between treatment groups.
In summary, these results indicate that most T2D patients in LTC facilities achieve and maintain good glycemic control without differences in A1C, fasting BG, BG within target and hypoglycemic events, when treated with basal insulin or OAD plus supplements.
Bullet 3: We know that improved glycemia has been shown to improve clinical outcomes and costs as it relates to diabetic complications; thus…as a diabetologists that has older patients, older parents and and only a decade away from getting a free coffee myself…I want to be cautiously aggressive in order to prevent complications and delay progress of undedrlying complications. I do agree that
FXCX:
AACE/ACE consensus statement: p543 c2 bullet2 under principles and p544 c1 under A1C goal
ADA/EASD consensus statement: A1C 7%: p194 c1 last para and p194 c1 para under glycemic goals
A1C 8%: ADA 2012 standards of care: p S19, col 1, 2nd bullet; outcomes from ACCORD, ADVANCE, VADT: pp S19-S21 [confirmed MT 1/20/2012]
Thank you Dr. Phillips for the introduction. I would also like to thank the ADA planning committee, members and guests for allowing me the opportunity to discuss the growing epidemic of diabetes in the older adult patient