Diabetes Control · 2019-03-19 · Objectives 1. Gain an understanding of the incidence and prevalence of diabetes in Ohio and across the nation. 2. Understand an overview and evidence

Diabetes Control

Kathleen Dungan, MD, MPHThe Ohio State University

Disclosures

• Research: Novo Nordisk, GSK, Astra Zeneca, Sanofi Aventis

• Consultant/advisory: GSK, Novo Nordisk, Eli Lilly, Sanofi Aventis, MannKind

• Royalties: UpToDate

Objectives

1. Gain an understanding of the incidence and prevalence of diabetes in Ohio and across the nation.

2. Understand an overview and evidence for current prediabetes and diabetes screening options

3. Become aware of treatment and care options for those patients having prediabetes and diabetes

4. Provided examples of systems, approaches and available tools to improve prediabetes and diabetes screening and control rates in community health centers.

Age-standardized Diabetes

Prevalence by County, 2012

Laura Dwyer-Lindgren et al. Dia Care

2016;39:1556-1562

Diagnosed

Undiagnosed

Total

Ohio

• United States

Trends in Diagnosed Diabetes, Ohio vs. US,

2018

https://www.americashealthrankings.org/explore/annual/measure/Diabetes/state/OH

Slide courtesy of Joshua Joseph, MD. The Ohio State University

Age-adjusted, county-level incidence of diagnosed diabetes among adults aged ≥20 years, United States, 2013

https://www.cdc.gov/diabetes/atlas/countydata/atlas.html


Columbus: Model-based estimates for diagnosed diabetes among adults aged >=18 years – 2016

500 Cities Project - https://nccd.cdc.gov/500_Cities/

Crude Prevalence %: 9.6

Crude 95% CI: 9.6-9.7

Age-Adjusted Prevalence %: 11.4

Age-Adjusted 95% CI: 11.4-11.5

2010 Census Population: 787,033


Age-standardized diabetes awareness and control by county,

2012.

Laura Dwyer-Lindgren et al. Dia Care 2016;39:1556-1562

% Aware of

Diagnosis

% under control

FBG <126 mg/dl or

HbA1c <6.5%

• 7th leading cause of death in US

• Leading cause of blindness

• Most frequent cause of kidney failure

• ~60% of nontraumatic lower limb amputations occur in people with diabetes

Diabetes Morbidity and Mortality

9CDC. National diabetes statistics report, 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf.

CDC. National diabetes fact sheet, 2011. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf.

Who to screen?

• >45 years old Overweight or obese adults with 1or more risk factors:

• High risk ethnicity• 1st degree relative with DM• CVD• GDM or baby > 9#• HTN• HDL <35 mg/dl• TG >250 mg/dl• PCOS• Physical inactivity• Condition associated with insulin

resistance (acanthosis nigricans)• Gestational Diabetes

Or

• Repeat screen

• every 3 years if normal

• annually if prediabetes

How Should we Screen?

Method Normal Prediabetes Diabetes

Fasting BG* <100 mg/dl 100-125 mg/dl ≥126 mg/dl

2 hr OGTT (75 gm)# <140 mg/dl 140-199 mg/dl ≥200 mg/dl

HbA1c <5.7% 5.7-6.4% ≥6.5%

Random BG - - Symptoms of DM & random

serum BG 200 mg/dl

*In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal

test results from the same sample or in two separate test samples.

http://www.diabetes.org/diabetes-

basics/prevention/diabetes-risk-test/

Diabetes Prevention Program

3200 adults with IGT + IFG

Standard Care Intensive Lifestyle• 7% weight reduction• Low-calorie, low fat diet• Exercise 150 min/week

Metformin

F/U 2.8 years

N Engl J Med. 2002 Feb 7;346(6):393-403.

Diabetes Prevention Program

• Metformin should be considered if‒ Very high risk:

• IGT + IFG

‒ Obese

‒ <60 years of age

% of P atients

developing Diabetes11

7.8

4.8

0

2

4

6

8

10

12

Usual

C are

Metformin L ifestyle

N Engl J Med. 2002 Feb 7;346(6):393-403.

A1C Achievement by Individualized Target

15

NHANES, National Health and Nutrition Examination Survey.

Ali MK, et al. N Engl J Med. 2013;368:1613-1624.

NHANES 2007-2010

(N=1444)

Age (years) 18-44 45-64 ≥65 ≥65 18-44 45-64 ≥65

Target A1C (%) ≤6.5 ≤7.0 ≤7.0 ≤7.5 ≤7.0 ≤8.0 ≤8.0

Without complications With complications

37.0

52.057.1

69.4

39.4

57.1

74.6

0

10

20

30

40

50

60

70

80

90

100

Pa

tie

nts

wit

h d

iab

ete

s (

%)

Meta-analysis: Intensive Glucose Control & Mortality

All-Cause Mortality

-0.2

-0.1

0

0.1

0.2

0.3

0.4

ACCORD ADVANCE UKPDS VADT Overall

Cardiovascular Death

-0.2

-0.1

0

0.1

0.2

0.3

0.4

ACCORD ADVANCE UKPDS VADT Overall

Fa

vo

rs m

ore

in

ten

siv

eF

avo

rs l

es

s in

ten

siv

e

P = 0.13 P = 0.04

Diabetologia 2009;52:2288-98

*

*

*p<0.05

After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007

Any diabetes related endpoint RRR: 12% 9%

P: 0.029 0.040

Microvascular disease RRR: 25% 24%

P: 0.0099 0.001

Myocardial infarction RRR: 16% 15%

P: 0.052 0.014

All-cause mortality RRR: 6% 13%

P: 0.44 0.007

RRR = Relative Risk Reduction, P = Log Rank

Legacy Effect of Earlier Glucose Control

Lower HigherGlucose

Target

Risk of hypoglycemia

Disease duration

Life expectancy

Major Comorbidities

Known cardiovascular

complications

Patient motivation and

capability

Resources and support

Low High

Newly diagnosed Long-standing

Long Short

Absent Severe

Absent Severe

High Low

Readily available Limited

Usually not

modifiable

Potentially

modifiable

ADA-Recommended Approach to Management of Hyperglycemia

Inzucchi SE, et al. Diabetes Care. 2015;38:140-149.

Measuring Success

ADA1

A1C <7%*

Fasting/preprandial BG 80-130

Postprandial BG <180 (peak)

*Goals should be individualized

Risks/Benefits of a “normal” A1c (< 6%) are unclear

1. ADA Clinical Practice Recommendations. Diabetes Care 30 (Supp. 1), 2007;

Patient-Centered Glycemic Management

Lifestyle

Comorbidities

Age, A1c, weight

Motivation

Culture/socioeconomic context

Individualized A1c

Weight, hypoglycemia

Side effect

Complexity, adherence

Access, cost

Educated patient

Seeks patient preference

Motivational interviewing

Goal setting

DSMESSMART Goals

• Specific

• Measurable

• Achievable

• Realistic

• Time Limited

Followup:

Not at goal: Q3Mo

At goal: Q6Mo

DSMES: more frequent

Well-being

Tolerability

Glucose control

Biofeedback: weight,

steps, BP, lipid

Review plan

Mutual agreement

Decision cycle repeated regularly to

avoid inertia

Davies et al. Dia Care 2018;41:2669-2701

Plasmaglucose

Insulin secretion

Hepaticglucoseoutput

Peripheralglucose uptake

-Glucosidase

inhibitors

GLP-1 RA

Pramlintide

Metformin

(glitazones)

Glitazones

(metformin)

Insulin

SFU

Glinides

GLP-1 RA

DPP-4 I

Glucose influx

Glucagon secretion

Incretins

Pramlintide

Matching Pharmacology to Physiology

Renal glucose excretion SGLT2

Inhibitor

CNS Neurotransmitter

dysfunction

Cycloset

American Diabetes Association. Diabetes Care. 2017;40(Suppl 1).

Antihyperglycemic Therapy in T2DMGeneral Recommendations (Part 1)In addition to lifestyle changes

FDA Update with Metformin

• Renal dosing

‒ contraindicated with eGFR <30 mL/minute/1.73 m2.

‒ Starting with eGFR 30-45 not recommended.

‒ Assess risks/benefits if eGFR falls <45

• Discontinue metformin before IV contrast if:

‒ eGFR 30-60

‒ liver disease

‒ Alcoholism

‒ heart failure

‒ intra-arterial contrast.

‒ evaluate eGFR 48 hours after the imaging procedure

Glitazone update

Rosiglitazone

• Meta-analysis1 of small trials, DREAM and ADOPT

‒ MI risk increased 43% (P=0.03)

‒ Risk of CV death was double the comparator (P=0.02)

• MI risk confirmed with longer-term meta-analysis2 but not RCT

Pioglitazone

• Meta-analysis3 of 19 trials‒ The primary outcome (death,

non-fatal MI, non-fatal stroke) was 18% LESS common with pioglitazone (P=0.005)

• IGT trial: reduced CV events

All prescribing restrictions imposed by the FDA have been lifted, except for CHF risk,

which is substantially increased with both rosiglitazone and pioglitazone

1. Nissen SE et al. N Engl J Med. 2007;356:2457-2471. 4. Singh S et al. JAMA. 2007;298:1189-1195.

2. Lincoff AM et al. JAMA. 2007;298:1180-1188. 5. Kernan et al. NEJM 2016; 374(14): 1321–1331.

3. Home et al. RECORD Trial. Lancet. 2009 Jun 20;373(9681):2125-35

https://www.ncbi.nlm.nih.gov/pubmed/19501900

DPP-4 Inhibitors

Name% HbA1c

ReductionRenal Dose Max Dose

Primary

effectCautions

Sitagliptin (Januvia®)

0.5-0.8

CrCl <30: 25 mg CrCl 30-50: 50 mg 100 mg daily

Increase

incretin

activity

Pancreatitis?

CHF?

Saxagliptin (Onglyza®) CrCl<50: 2.5 mg 5 mg daily

Linagliptin ( Tradjenta®) 5 mg daily 5 mg daily

Alogliptin (Nesina®)CrCl 30-60: 12.5mgCrCl <30: 6.25 mg 25 mg daily

No added hypoglycemia unless used with secretagogue or insulin

Weight neutral

Well-tolerated

SGLT2 Inhibitors

Name% HbA1c

Reduction

Starting

DoseMax Dose

Primary

effectCautions

Canagliflozin

(Invokana®)

0.5−1.0

100 mg daily300 mg

daily

Block renal

glucose

reabsorption

Ineffective if

eGFR <45 (C, E)

or <60 (D), UG

infection,

fluid/electrolyte,

euglycemic DKA

Amputation (C)

Empagliflozin

(Jardiance®)10 mg daily 25 mg daily

Dapagliflozin

(Farxiga®)5 mg daily 10 mg daily

Ertugliflozin

(Steglatro®)5 mg daily 15 mg daily

Modest blood pressure, weight reduction

No hypoglycemia

Generic Name

Brand Name Dose forms

HbA1c Reduction

Dosing Interval Cautions

Exenatide BID

Byetta 5, 10 µg

1-2%

BID

C-cell tumors/ MEN-2, advanced CKD, gastroparesis,pancreatitis?

Lixisenatide Lyxumia 10, 20 µg QD

Liraglutide Victoza1.6, 1.2, 1.8 µg

Daily

ExenatideQW

Bydureon 2 mg Weekly

Semaglutide Ozempic 0.5, 1.0 mg Weekly

Dulaglutide Trulicity 0.75, 1.5 mg Weekly

GLP-1 receptor agonists

• No inherent hypoglycemia

• Modest weight and BP reduction

• Nausea/vomiting, usually self-limitedGLP-1 R

Activation

Intermittent

Continuous

Efficacy of GLP-1 RA

Andreadis et al. Diabetes Obes Metab. 2018 May 13. doi: 10.1111/dom.13361. [Epub ahead of print]

Exenatide QW

Sitagliptin

Glargine

Oral agent

Liraglutide

DulaglutideSitagliptin

American Diabetes Association Standards of Care

ASCVD

HypoglycemiaHF or CKD

Weight Loss Cost


Choosing glucose-lowering medication in established ASCVD, HF, and CKD


Completed and ongoing CVOTs

3-P, 3-point; 4-P, 4-point; 5-P, 5-point.

William T. Cefalu et al. Dia Care 2018;41:14-31

Effects of Glucose-lowering agents on Outcomes

Study Anti-Diabetic Drug

CV Outcomes

HR+ P-value Microvascular outcomes

PROactive Pioglitazone 0.84 0.02 NA

ORIGIN Insulin glargine 1.02 NS Reduced composite (renal

and retinal) in A1c >6.4

SAVOR Saxagliptin 1.00 NS Reduced renal

EXAMINE Alogliptin 0.96 NS NA

TECOS Sitagliptin 0.98 NS No effect on renal

EMPA-REG Empagliflozin 0.86 0.04 Reduced renal

CANVAS Canagliflozin 0.86 0.02 Reduced renal

Increased amputation

ELIXA Lixisenatide 1.02 NS Possibly reduced renal

LEADER Liraglutide 0.87 0.01 Reduced renal

EXSCEL Exenatide weekly 0.91 0.06 NA

SUSTAIN-6 Semaglutide 0.74 0.02* Reduced renal

Increased retinopathy

J Diabetes Complications 2014;28:430-433

Cefalu et al. Diabetes Care 2018 Jan; 41(1): 14-31

+CV mortality, nonfatal AMI, nonfatal stroke

SGLT2I demonstrate reductions in hospitalization for HF

*testing for superiority not pre-specified

TZD

Insulin

DPP-4

Inhibitors

SGLT2

Inhibitor

GLP-1

RA

Glucose-lowering Medication If Cost Is a Major Issue.


MetforminIf A1c >1.5% above target consider early combination

If patient has

private

insurance, use

co-pay cards

Glucose-lowering Medication if Compelling Need for Weight Loss


MetforminIf A1c >1.5% above target consider

early combination

GLP-1RA SGLT2i

SGLT2i GLP-1RA

DPP-4i

Cautious use of SFU, TZD, basal

insulin

Lifestyle

advice

Weight

loss

medicat

ion

Metabol

ic

surgery

Caloric

restriction

Evidence-

based

weight

loss

programs

Glucose-lowering Medication If Compelling Need to Minimize Hypoglycemia


MetforminIf A1c >1.5% above target consider early

combination

0

1

2

3

4

5

6

7

Metformin,DPP-4I,

GLP-1 RA,SGLT2I,

TZD

Glinides Sulfonylurea Basal insulin Basal bolus,premix

% of Patients Treated Over 1 Year1

1) Moghissi E, et al. Endocr Pract. 2013;19:526-535.

Frequency of Severe Hypoglycemia With Antihyperglycemic Agents

• HbA1c and duration of DM is

not a significant predictor2

• Duration of insulin therapy

associated with overall,

nocturnal and severe

hypoglycaemia

• Premix and prandial insulin

associated with more

hypoglycemia and weight gain

than basal insulin3

2) Khunti et al. Diabetes Obes Metab. 2016;18(9):907-15

3) Giugliano et al. Diabetes Care 34:510–517, 2011

Intensifying to Injectable Therapies

Consider initial combination injection if

A1c>10 or >2% above target

Consider initial

insulin if A1c>11,

T1D is possibility,

or Symptomatic

Consider Fixed

ratio combination

basal insulin

+GLP-1RA

GLP-1RA

A1c above target despite

dual/triple Rx

A1c > target

Basal InsulinTitration

• Self-titration more

effective

• Eg: ↑2 unit every

3 day until BG at

target without

lows

Initiation: 10 unit or

0.1-0.2 unit/kg/d


Already on GLP-1RA,

GLP-1RA not

appropriate or insulin

preferred

GLP-1RA or Basal Insulin?

Abd El Aziz, Diabetes Obes Metabl 2017;19(2):216-227

HbA1c:Treatment difference

0.12% (p<0.0001)

Driven by long-acting

GLP-1RA

Hypoglycemia: 15% less

(p<0.0001)

Exenatide BID

Exenatide QW

Albiglutide

Liraglutide

Dulaglutide

Weight:Treatment

difference 3.7 kg

(p<0.0001)

Short-acting GLP-1RA Basal

Long-acting GLP-1RA Basal

Short-acting GLP-1RA Basal

Long-acting GLP-1RA Basal

20 10 0 10 20 30

Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota.

Years of Diabetes

Relative -Cell

Function

Plasma

Glucose

Insulin resistance

Insulin secretion

126 mg/dL Fasting glucose

Postmeal

glucose

6-6

Natural History of T2DM

• Loss of beta cell function begins before diagnosis and progresses

• Insulin resistance does not change over time

Basal insulins:Practical Aspects

Preparation

Action

Duration Vial

Disposable Pens

Dosing Range per

injection (Unit)

Dosing

Increment per

Injection

(Unit) Dispensing Amount

Basal Insulin

NPH daily or bid 10-20 hr10 mL,

1000 unitKwikpen: 1-60 1 Pen: 3 ml, 300 unit

Detemir daily or bidUp to 24

hr

10 mL,

1000 unitFlextouch: 1-80 1 Pen: 3 ml, 300 unit

Glargine daily (U100)Approx

24 hr

10 mL,

1000 unitSolostar: 1-80 1 Pen: 3 ml, 300 unit

Glargine daily (U300) 30 hr N/ASolostar: 1-80

Max Solostar: 2-160

1

2

Pen: 1.5 ml, 450 unit

Pen: 3 ml, 900 unit

Degludec daily (U100) 30 hr N/A Flextouch: 1-80 1 Pen: 3 ml, 300 unit

Degludec daily (U200) 30 hr N/A Flextouch: 2-160 2 Pen: 3 ml, 600 unit

Re

lative

In

su

lin E

ffe

ct

Re

lative

In

su

lin E

ffe

ct

Re

lative

In

su

lin E

ffe

ct

Re

lative

In

su

lin E

ffe

ct

A B

C D

0 12 24

0 12 24 0 12 24

0 12 24Time (h) Time (h)

Time (h)Time (h)

Insulin glargine Insulin glargine

Insulin glargineInsulin glargine 100 units/ml

NPH insulin

Insulin detemir

Insulin degludecInsulin glargine 300 units/ml

Ultra-Long-Acting Insulins

Key Features:

• Flatter profile

• Longer duration

• Less hypoglycemia

• Once daily, flexible

Pettus et al. Diabetes Metab Res Rev 2015;

Combination GLP-1RA +Basal insulin

• Additive HbA1c reductions with GLP-1RA +Basal

• Similar HbA1c reduction with less hypoglycemia/ weight gain with GLP-1RA compared to prandial insulin

Maria Ida Maiorino et al. Dia Care 2017;40:614-624

GLP-1RA + Basal Basal

GLP-1RA + Basal Basal + Prandial

Fixed Ratio GLP-1RA + Basal Basal or GLP-1RA

Fixed-Ratio GLP-1RA and Basal Insulin

Product Brand

Insulin to

GLP-1 RA

Ratio

How

Supplied Starting dose

Maximum

dose

Insulin glargine/

lixisenatide

100/33

Soliqua1 Units/0.33

mcg

3 mL prefilled

pen

If basal dose

• <30 Units/day:

start 15 Units.

• ≥30 Units/day:

start 30 Units.

60 Units/20

mcg

Insulin degludec/

liraglutide 100/3.6Xultophy

1 Units/0.036

mg

3 mL prefilled

pen16 unit/day

50 Units/1.8

mg

Oral therapy in combination with injectable therapies


• Metformin: continue

• DPP4i: stop if using GLP-1RA

• SFU: stop or reduce dose 50% with insulin

• TZD: stop or reduce dose with insulin

• SGLT2i: continue but beware of DKA in insulin requiring patients, provide sick day rules

Intensifying to injectable therapies


A1c > target despite basal

titration or dose >0.7-1.0 unit/kg

or FBG at target

Initiation: 4 unit or

10% of basal

If A1c <8 consider

↓basal

Prandial insulin

1 injection/day at largest meal

or largest PPG excursionTitration

Increase 1-2 unit or

10-15% 2x/week

A1c > target

Consider

Premix BID

or TID

Higher risk

of

hypoglycemi

a/weight

gain

A1c > target

Stepwise addition of prandial

injections

• Consider DSME

• Consider insulin sparing Rx

• Consider concentrated insulin

• Review adherence, simplify

Optimizing your insulin

• Hypoglycemia mitigation

‒ Manage carbohydrates, activity

‒ Insulin analogues

‒ Ultra-long acting insulins (if needed)

‒ Combine with GLP-1 RA

‒ Combine with other oral agents (DPP-4 Inhibitor or SGLT2 Inhibitor)

Chronic Care Model

• 6 core elements

‒ Delivery system design

‒ Self-management support

‒ Clinical information systems

‒ Community resources and policies

‒ Health systems

American Diabetes Association Standards of Care; Diabetes Care 2019

Thank You

Health Partners of Western Ohio

15 Care Sites (4 School Based)

Integrated Model of CarePCP, BH, ClinPharm, Support StaffSocial Services, Outreach

Workers, Dispensing Pharmacy, Dental, Chiropractic,

Medical and Dental Outreach Programs

5 In-House Pharmacies

2018: 38,127 Patients

154,170 Visits

“To eliminate gaps in health outcomes for all members of our community by

providing access to quality, affordable, preventive and primary health care.”

2017 UDS: 34,114 Patients

Patient

PCP

BH

CPS

Social Servic

es

Outreach / CM

Chiro

Dental

Integrated Model of Care

Diabetes Practice Pearls• Pre-DM Screening and Education

• Team Based Care

• Population Health Management

• Quality Transparency

• Access to Medication: • In house pharmacies• contract pharmacies

• Access to Lab Testing: • POC testing in clinic• Lab services on-site

Documents

Diabetes Control · 2019-03-19 · Objectives 1. Gain an understanding of the incidence and prevalence of diabetes in Ohio and across the nation. 2. Understand an overview and evidence