Fall Quality Summit

diabetes in the elderly

Michael Shannon, MD

Endocrinologist and PSW Medical Director

- Fall Quality Summit Agenda -

Welcome!

6:00 – 6:30 Networking & Appetizers

6:30 – 6:40 Dr. Gary Goin, MD

• Introductions

6:40 – 7:30 Michael Shannon, MD

• Rational Goal-Setting and

Management of Diabetes in Elderly

Dr. Michael Shannon

Michael H. Shannon, MD, is an

endocrinologist and Medical Director with

Physicians of Southwest Washington, an

Independent Practice Association managing

Medicare Advantage and ACO contracts, in

Olympia, Washington.

He is a Clinical Assistant Professor in the

Department of Medicine at the University of

Washington.

He serves on the Editorial Board of Clinical

Diabetes, and he is the Chair of the

Professional Education Committee for the

Washington chapter of the American

Diabetes Association.

Rational Goal-Setting and Management

of Diabetes in the Elderly

Michael Shannon, MD

Medical Director, Physicians of Southwest Washington

Clinical Assistant Professor, University of Washington

Outline of Talk

Challenges of diabetes care in the elderly Goal setting and A1c targets in elderly Interpret studies for diabetes agents

cardiovascular safety, released in last 48 months Current guidelines (ADA-EASD, AACE) and

review of treatment options for elderly

Disclosure: Speaker and Consultant, Novo Nordisk

and BI/Lilly Alliance

Epidemiology of Diabetes in Elderly

Estimated at 26% for those aged 65+

Long term care (2007-13): multiple studies

cite 25-34% in LTC facilities (SNF and ALF)

Several Challenges in Managing These Patients

Hypoglycemia in the Elderly

Presentation overlaps other frailty syndromes

Confusion, word-finding errors, altered LOC

Tremors / dizziness

No one goes wrong getting a UA and Fingerstick

Limited ability to self-manage hypoglycemia

Limited vision/transfer ability to self-rescue

Increased fall risk, sedation from other medication

In institution, limited access to self-correction

Hyperglycemia in the Elderly

Symptomatic hyperglycemia

Polyuria: glycosuria load, UTI risk

Dehydration (impaired thirst, impaired access)

Blurry vision (increased falls)

Impaired wound healing

Unlike hypoglycemia, these are more subtle

and slower to emerge -> need more vigilance

Polypharmacy and Complex PMH

Increases Hyperglycemia

Steroids

Antipsychotics

Infections / immobility

Increases Hypoglycemia

Sedative Agents

Renal impairment

Poor nutrition

Cirrhosis (limited synthesis)

Diabetes Assessment in the Elderly

Goal-Setting for General Diabetes Plan

Physical Assessment

Nutritional Assessment

Physical Assessment

11

Nutritional Assessment

Malnutrition Poverty / isolation

Dentition

WWII Widower

Depression

Cognitive Impairment

12

Physical Assessment

Ophthalmic

Higher rates of cataracts, glaucoma and macular

degeneration.

Dexterity/Hands:

Vials vs pens, choice of meters

General Home Safety Eval (cords, rugs, cats)

A1c Goals in the Elderly

Standards of

Medical Care in

Diabetes - 2019

A1C Goals in Adults: Recommendations (2)

• Less stringent goals (such as <8% [64 mmol/mol]) may

be appropriate for patients with a history of severe

hypoglycemia, limited life expectancy, advanced

microvascular or macrovascular complications, or long-

standing diabetes in whom the goal is difficult to achieve

despite diabetes self-management education,

appropriate glucose monitoring, and effective doses of

multiple glucose-lowering agents including insulin. B

Approach to the Management of Hyperglycemia

low high

newly diagnosed long-standing

long short

absent severeFew/mild

absent severeFew/mild

highly motivated, adherent, excellent self-care capabilities

readily available limited

less motivated, nonadherent, poor self-care capabilities

A1C7%

more stringent

less stringentPatient/Disease Features

Risk of hypoglycemia/drug adverse effects

Disease Duration

Life expectancy

Important comorbidities

Established vascular complications

Patient attitude & expected

treatment efforts

Resources & support system

Glycemic Targets:

Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S55-S64

Elderly DM Goals: My 3 Levels

For those with good functional status, same as

others post-ACCORD study (probably about

7-7.5% depending on CV disease)

For life expectancy < 5 years, < 8%

For palliative care patients: avoid symptoms

Glucose > 180 = glycosuria, dehydration, UTIs

Glucose over ~225 = poor wound healing,

increased decubitus ulcers

Diabetes: Recent CV Outcome Trials

Landmark Trials for Elderly DM

DCCT: For DM1, enrolled people < 39 years of age

UKPDS: did not enroll past 59 years of age

Last round of trials without CV benefit include

ACCORD (mean age 62), VADT (mean age 60), and

ADVANCE (mean age 66) but few > 75 years old

No outcome trial focused on elderly (no HYVET)

No major trials at all for frail/institutionalized elderly

Empagliflozin, Cardiovascular Outcomes, and

Mortality in Type 2 Diabetes

Addition of empagliflozin, an SGLT2 inhibitor, to

individuals with DM2 and established CVD (Prior

myocardial infarction, coronary artery disease, stroke,

unstable angina or occlusive peripheral arterial disease)

7000 patients, mean age 63, 72% male

Criteria: BMI < 45, A1c 7-10%, CrCl > 30

B Zinman et al, NEJM 2015

Patients with event/analysed

Empagliflozin Placebo HR (95% CI) p-value

3-point MACE 490/4687 282/2333 0.86(0.74,

0.99)*0.0382

CV death 172/4687 137/2333 0.62 (0.49, 0.77) <0.0001

Non-fatal MI 213/4687 121/2333 0.87 (0.70, 1.09) 0.2189

Non-fatal stroke 150/4687 60/2333 1.24 (0.92, 1.67) 0.1638

0.25 0.50 1.00 2.00

EMPA REG: CV death, MI, stroke

Favours empagliflozin Favours placebo

EMPA REG by Age

EMPA-REG OUTCOME: Summary

Empagliflozin reduced risk for 3-point MACE by 14%

Empagliflozin reduced hospitalization for heart failure

by 35%

Empagliflozin reduced CV death by 38%

Empagliflozin improved survival by reducing all-cause

mortality by 32%

Increase in genital infections, otherwise well tolerated

LEADER - Analysis by Age

Clinical Outcomes with Canagliflozin

N=10,142 patients with T2D and high CV risk CANVAS: n=4330

CANVAS-R: n=5812

Endpoints Primary endpoint: composite of CV death, nonfatal

MI, or nonfatal stroke

Secondary endpoints: All-cause death

CV death

Albuminuria progression

Composite of CV death and HF hospitalization

CANVAS Program Study Design

Neal B, et al. N Engl J Med. 2017;377:644-657.

Hazard ratio (95% CI) P value

Primary composite endpoint* 0.86 (0.75-0.97) 0.02†

CV death 0.87 (0.72-1.06)

Nonfatal MI 0.85 (0.69-1.05)

Nonfatal stroke 0.90 (0.71-1.15)

Fatal or nonfatal MI 0.89 (0.73-1.09)

Fatal or nonfatal stroke 0.87 (0.69-1.09)

HF hospitalization 0.67 (0.52-0.87)

CV death or HF hospitalization 0.78 (0.67-0.91)

All-cause death 0.87 (0.74-1.01)

Progression of albuminuria 0.73 (0.67-0.79)

40% reduction in eGFR, renal replacement

therapy, or renal death

0.60 (0.47-0.77)

Clinical Outcomes with CanagliflozinCANVAS Program

(N=10,142)

Neal B, et al. N Engl J Med. 2017 Jun 12 [epub ahead of print].

0.00 0.50 1.00 1.50

Favors canagliflozin

Adverse Events with CanagliflozinCANVAS Program* Safety Results

*Includes patients from CANVAS and CANVAS-R (N=10,142). †CANVAS-only population (n=4330).

Neal B, et al. N Engl J Med. 2017 Jun 12 [epub ahead of print].

Event Canagliflozin Placebo P value

Events per 1000-patient years

All serious adverse events 104.3 120.0 0.04

Adverse events leading to discontinuation 35.5 32.8 0.07

Diabetic ketoacidosis (adjudicated) 0.6 0.3 0.14

Events of interest occurring in significantly more canagliflozin-treated patients

Amputation 6.3 3.4 <0.001

Bone fracture (adjudicated)

All 15.4 11.9 0.02

Low trauma 11.6 9.2 0.06

Infection of male genitalia 34.9 10.8 <0.001

Osmotic diuresis† 34.5 13.3 <0.001

Volume depletion† 26.0 18.5 0.009

Mycotic genital infection in women† 68.8 17.5 <0.001

Diagnosis is a fairly soft endpoint,

but death is unequivocal.

Edwin AM Gale, Lancet 2003

ADA 2019 Cardiovascular Disease:

Treatment

10.39 Among patients with type 2 diabetes who have established

atherosclerotic cardiovascular disease, sodium-glucose

cotransporter 2 inhibitors or glucagon-like peptide 1 receptor

agonists with demonstrated cardiovascular disease benefit

(Table 9.1) are recommended as part of the antihyperglycemic

regimen. A

10.40 Among patients with atherosclerotic cardiovascular

disease at high risk for heart failure or in whom heart failure

coexists, sodium-glucose cotransport 2 inhibitors are

preferred. C

Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes - 2019. Diabetes Care 2019;42(Suppl. 1):S103-S123

• In patients with T2DM and established ASCVD, antihyperglycemic therapy should begin with lifestyle management and metformin and subsequently incorporate an agent proven to reduce major adverse CV events and CV mortality (currently empagliflozin and liraglutide), after considering drug-specific and patient factors (Table 8.1). A

• In patients with T2DM and established ASCVD, after lifestyle management and metformin, the antihyperglycemic agent canagliflozin may be considered to reduce major adverse CV events, based on drug-specific and patient factors (Table 8.1). C

Pharmacologic Approaches to Glycemic Treatment:

Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85

Pharmacologic Therapy For T2DM: Recommendations (4)

Guidelines: AACE vs ADA (vs me)

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2019. Diabetes Care 2019;42(Suppl. 1):S90-S102

41

42

• If A1C is above target despite

recommended first-line treatment and

the patient has ASCVD or CKD:

• ASCVD Predominates:

• Add GLP-1 RA with proven CVD

benefit, OR

• Add SGLT-2 inhibitor with proven

CVD benefit (if eGFR adequate)

• If HF or CKD Predominates:

• Add SGLT-2 inhibitor with

evidence of benefit

• If can’t take an SGLT-2 inhibitor,

use a GLP-1 RA with proven CVD

benefit

43

44

2018 ACC Expert Consensus Decision Pathway on Novel Therapies for CV Risk Reduction in Patients With Type 2 Diabetes and ASCVD (Fig 2)

The Diabetes Toolbox 2019

Drug Class (First in Class) FDA Approval

Insulin (subcutaneous) 1922 (first use)

Sulfonylurea (chlorpropamide) 1958

Biguanide (metformin) 1995

Alpha-glucosidase inhibitors (acarbose) 1995

Thiazolidinedione (troglitazone) 1997

Meglitinide (repaglinide) 1997

Incretins (pramlintide, exenatide) 2005

DPP-IV Inhibitors (sitagliptin) 2006

Bile acid sequestrant (colesevelam) 2008 (DM)

Dopamine agonist (bromocriptine QR) 2009

SGLT-2 inhibitor (canagliflozin) 2013

The Toolbox in 2019

Metformin: great – with new GFR guidance –

please use metformin ER

Sulfonylureas: cheap, but risk of

hypoglycemia; no more glyburide (and its evil

metabolite norglyburide cleared through

kidneys) -> now $4 monthly glimepiride

TZDs: no hypoglycemia but risks of edema,

CHF, and possibly fractures and malignancies

Available for Q&A: colesevelam, bromocriptine

Metformin

FDA (April 2016): “We have concluded

from the review of studies published in the

medical literature that metformin can be

used safely in patients with mild impairment

in kidney function and in some patients with

moderate impairment in kidney function.”

Label update: now “contraindicated” if

eGFR is <30mL/min/1.73m2

2014 update from the International Society

of Nephrology: metformin may still be

appropriate for eGFR 14-29mL/min/1.73m2

GLP-1 Agonists

Modest benefit in HbA1c 0.7-1.1% and some

weight loss as well but some nausea

Safety warnings about pancreatitis and

medullary thyroid cancer

Cardiovascular studies complete for several

Can be used in combination with basal insulin

at same time of day, for probably best efficacy

with reasonably low risk of hypoglycemia

Most have CV studies

DPP-IV Inhibitors

Sitagliptin, saxagliptin, linagliptin, alogliptin

Modest decrease in HbA1c of 0.5% - 0.8%;

Minimal side effects (possible more minor

infections) except saxagliptin showed increased

congestive heart failure (seen in ADA guideline)

SGLT-2 Inhibitors

Approved starting in 2013; blocks renal re-

absorption of glucose and lowers blood sugars

Associated with similar modest HbA1c decrease

of 0.5% - 0.7%) as DPP-IV inhbitors (UTDOL)

Risks: infections and dehydration, DKA

Independent of resistance (can use with insulin)

but limit dose eGFR 45-60 and don’t use < eGFR

45 or with hepatic impairment

CV Studies: EMPA REG, CANVAS, DECLARE

Final Words on Newer Agents

None of these have been in wide use for long

Lessons of rosiglitazone: hemoglobin A1c is

a surrogate endpoint, not the true goal of care

All the new drugs cost upwards of $10/day

Final Words on Newer Agents

None of these have been in wide use for long

Lessons of rosiglitazone: hemoglobin A1c is

a surrogate endpoint, not the true goal of care

All the new drugs cost upwards of $10/day

For elderly, hypoglycemia safety probably is

main reason to use, or dosing convenience,

EXCEPT with coexisting CV disease, choose

one of the ADA and ACC recommended Rx

Indications for Insulin Therapy

Severe hyperglycemia at diagnosis

Hyperglycemia despite maximum doses of

non-insulin agents

Decompensation of other organ systems that

limits use of other oral agents

Early potent treatment with non-hypo safety

Combination Injectable Therapy in T2DM

To Infinity and Beyond

Insulin Pens = KEY for elderly (easier than

ever: CTS, visual impairment, neuropathy)

Insulin pumps appropriate if motivated and

fulfill strict Medicare criteria

Continuous monitors approved for Medicare

AMDA has excellent LTC guidelines for also

incorporating multidiscipinary team

Conclusion

Diabetes is common in the elderly and care of

these individuals is more challenging

ADA and AACE have slightly different goals

of care and treatment pathways, and toolbox

can be viewed with focus on elderly

Multiple new cardiovascular studies support

the preferential use of certain GLP-1 and

SGLT-2 drugs for those with DM & CVD

Questions and Appreciation