Insulin Pump ManagementConsensus Statement by the AACE/ACE Insulin Pump Management Task Force

George Grunberger, MD, FACP, FACE*Jill M. Abelseth, MD, FACE

Timothy S. Bailey, MD, FACP, FACE, ECNUBruce W. Bode, MD, FACE

Yehuda Handelsman, MD, FACP, FACE, FNLA Richard Hellman, MD, FACP, FACE

Lois Jovanovič, MD, MACEWendy S. Lane, MD

Philip Raskin, MD, FACEWilliam V. Tamborlane, MD

ENDOCRINE PRACTICE: TBD

Presentation OutlineIntroductionPreambleState of Insulin Pump TechnologyClinical Evidence Patient and Provider SelectionInsulin Pump Use in Various Patient PopulationsEducation and TrainingPatient Safety IssuesCoding and Reimbursement Issues in PracticeEconomics of Insulin Pump TherapyFuture Needs and Conclusions

Introduction

IntroductionFirst AACE consensus statement on insulin pump

management published in 2010Current consensus statement includes:

Extensive updates on state of insulin pump technology Expanded discussion of CSII in pediatric patientsData on use of concentrated regular U-500 insulin in

CSII Discussion on need to develop uniform trainingSuggestions of what uniform training should cover Discussion of device-related pump problemsImpact of patient selection and education on safe CSII

use

AACE: American Association of Clinical EndocrinologistsCSII: continuous subcutaneous insulin infusion

Preamble

Preamble Roughly 20% - 30% of patients with T1DM and

fewer than 1% of insulin-treated patients with T2DM use an insulin pump

In 2007, the US FDA estimated that the number of patients with T1DM using CSII was ~375,000

By 2050, up to one-third of US residents may have T2DM; many of these individuals will be insulin-requiring

Therefore, more clinicians must develop a comprehensive understanding of these devices

HSBC Global Research. Healthcare US Equipment & Supplies. 2005.U.S. FDA. General Hospital and Personal Use Medical Devices Panel. 2010U.S. CDC. CDC Media Relations - Press Release: October 22, 2010.

T1DM: type 1 diabetes mellitusT2DM: type 2 diabetes mellitus

FDA: U.S. Food and Drug AdministrationCSII: continuous subcutaneous insulin infusion

State of Insulin Pump Technology

State of Insulin Pump TechnologyInsulin pumps now include features such as

Color touch screensUSB-rechargeable batteriesPre-filled insulin cartridges, and Disposability

The availability of multiple infusion set types, choices of catheter tubing lengths, and tubeless pumps have enhanced pump therapy accessibility and led to increased pump usage

Current Developments in Insulin Pump TechnologyClinical trials are underway to validate methods

that accelerate insulin action Data supporting the feasibility of locating infusion

sets and CGM catheters in close proximity make it likely that combination sensor and infusion sets will be developed

Insulin pumps can now display CGM data on the same screen and share display data on other remote devices

Medtronic’s MiniMed 530G with Enlite (approved in 2013) is the first device that alters insulin delivery in response to CGM sensor data

CGM: continuous glucose monitoring

Accu-Chek

Combo System

Asante Snap

Insulin Pump

System

MiniMed Paradigm Real-Time Revel

System (523/723

)

MiniMed 530G with

Enlite (551/751

)

OmniPod Insulin Manage-

ment System

OneTouch Ping

t:slim Insulin Pump

V-Go Disposab

le Insulin Delivery Device

Roche Health Solutions

Asante Solutions

Medtronic MiniMed

Medtronic MiniMed

Insulet Corporation

Animas Tandem Diabetes Care

Valeritas, Inc.

Insulin Pumps on the Market

Clinical Evidence for Insulin Pump Therapy in Diabetes

Type 1 DiabetesA 2010 Cochrane review compared the use of

CSII vs. MDI insulin regimens (23 randomized studies involving 976 patients with T1DM)A significant difference was documented in

HbA1c response, favoring CSIICSII users demonstrated greater

improvements in quality of life measures Severe hypoglycemia appeared to be reduced

in CSII usersCSII: continuous subcutaneous insulin infusion

MDI: multiple daily injectionT1DM: type 1 diabetes mellitus

Misso ML, et al. Cochrane Database Syst Rev. 2010;(1):CD005103. doi(1):CD005103

Type 1 DiabetesThe STAR-3 study showed significantly

greater HbA1c reductions in patients with T1DM randomly assigned to sensor-augmented insulin pump therapy vs. MDIA higher proportion of patients randomly

assigned to pump therapy achieved an HbA1c <7% without any increase in severe hypoglycemia rates or weight gain vs. the MDI group

Based on currently available data, CSII is justified for basal-bolus insulin therapy in patients with T1DM

STAR-3: Sensor-Augmented Pump Therapy for A1C ReductionT1DM: type 1 diabetes mellitus

MDI: multiple daily injectionCSII: continuous subcutaneous insulin infusion

Bergenstal RM, et al. N Engl J Med. 2010;363(4):311-320

Key Findings: CSII Meta-Analyses (T1DM and T2DM) Published Since 2003

Reference Findings

Weissberg-Benchell et al, Diabetes Care. 2003;26(4):1079-

1087

Compared with MDI, CSII therapy was associated with significant improvements in glycemic control based on HbA1c and mean blood glucose decreases

Jeitler et al, Diabetologia. 2008;51(6):941-951

HbA1c reduction greater and insulin requirements lower with CSII than with MDI in adults and adolescents with T1DM; hypoglycemia risk comparable among adult patients (data unavailable for adolescent subjects); no conclusive CSII benefits for patients with T2DM

Fatourechi et al,J Clin Endocrinol Metab.

2009;94(3):729-740

In patients with T1DM, HbA1c was mildly decreased with CSII vs. MDI; CSII effect on hypoglycemia unclear; similar CSII and MDI outcomes among patients with T2DM

Pickup and Sutton, Diabet Med. 2008;25(7):765-774

HbA1c was lower for CSII than for MDI, with greatest improvement in patients with highest initial HbA1c values on MDI; severe hypoglycemia risk was decreased with CSII vs. MDI; greatest reduction in patients with diabetes of longest duration and/or highest baseline rates of severe hypoglycemia

Monami et al,Exp Clin Endocrinol Diabetes.

2009;117(5):220-222

HbA1c was significantly lower with CSII vs. MDI; HbA1c reduction was only evident for studies with mean patient age >10 years; severe hypoglycemia occurred at comparable rates with CSII and MDI therapy

CSII, continuous subcutaneous insulin infusion; DKA, diabetic ketoacidosis; HbA1c, hemoglobin A1c; MDI, multiple daily injections; RCT, randomized controlled trial; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus

Type 2 DiabetesFewer clinical investigations have examined

CSII in patients with T2DM In an analysis of four randomized controlled

trials involving patients with T2DM:No significant HbA1c improvements, differences

in hypoglycemic risk, or weight differences were observed with CSII vs. MDI over 12 to 52 weeks

CSII: continuous subcutaneous insulin infusionT2DM: type 2 diabetes mellitus

MDI: multiple daily injectionBode BW. Diabetes Technol Ther. 2010;12 Suppl 1:S17-21.

Randomized Clinical Trials Comparing CSII and MDI for Patients With T2DM

HbA1c (%)

Reference Design Baseline CSII MDI P-value

Noh et al, Diabetes Metab Res Rev. 2008;24(5):384-391.

30-week observational study (N=15)

7.9 5.0 NA <0.001

Parkner et al, Diabetes Obes Metab. 2008;10(7):556-563.

Observational study, 3 successive nights (N=10)

Fasting plasma glucose: 209 mg/dL

99.1 mg/dL

NA <0.0001

Berthe et al, Horm Metab Res. 2007;39(3):224-229.

Crossover study, 2 12-week periods (N=17)

9.0 7.7 8.6 <0.03

Herman et al, Diabetes Care. 2005;28(7):1568-1573.

1 year parallel study (N=107) CSII: 8.4 MDI: 8.1

6.6 6.4 0.19

Raskin et al, Diabetes Care. 2003;26(9):2598-2603

24 week parallel study (N=132)

CSII: 8.2 MDI: 8.0

7.6 7.5 NS

Wainstein et al, Diabet Med. 2005;22(8):1037-1046.

Crossover study, 2 18-week periods (N=40)

CSII-MDI: 10.1 MDI-CSII 10.2

−0.8 +0.4 0.007

CSII: continuous subcutaneous insulin infusion; MDI: multiple daily injection; T2DM: type 2 diabetes mellitus

Patient Selection for CSII

Characteristics of the Ideal CSII CandidateThe ideal CSII candidate is:

A patient with T1DM or intensively managed insulin-dependent T2DM

Currently performing ≥4 insulin injections and ≥4 SMBG measurements daily

Motivated to achieve tighter blood glucose controlWilling and intellectually and physically able to

undergo the rigors of insulin pump therapy initiation and maintenance

Willing to maintain frequent contact with their health care team CSII: continuous subcutaneous insulin infusion

T1DM: type 1 diabetes mellitusT2DM: type 2 diabetes mellitus

SMBG: self-monitored blood glucose

Specific Characteristics of Patients Who Are Not Good Candidates for Insulin Pump Use Unable or unwilling to perform MDI injections (≥3 to 4

daily), frequent SMBG (≥4 or 5 daily), and carbohydrate counting

Lack of motivation to achieve tighter glucose control and/or a history of non-adherence to insulin injection protocols

History of serious psychological or psychiatric condition(s) (e.g., psychosis, severe anxiety, or depression)

Substantial reservations about pump usage interfering with lifestyle (e.g., contact sports or sexual activity)

Unrealistic expectations of pump therapy (e.g., belief that it eliminates the need to be responsible for diabetes management)

MDI: multiple daily injectionSMBG: self-monitored blood glucose

Patients with T1DM who do not reach glycemic goals despite adherence to a maximum MDI, especially if they have:Very labile diabetes Frequent severe hypoglycemia and/or hypoglycemia

unawarenessSignificant “dawn phenomenon,” extreme insulin

sensitivityPatients with T1DM who feel that CSII would be

helpful in managing their diabetesSpecial populations (e.g., preconception, pregnancy,

children, adolescents, competitive athletes)

T1DM: type 1 diabetes mellitusMDI: multiple daily injection

CSII: continuous subcutaneous insulin infusion

Proposed Clinical Characteristics of Suitable Insulin Pump Candidates – T1DM Patients

Proposed Clinical Characteristics of Suitable Insulin Pump Candidates – T2DM Patients

Selected patients with insulin-requiring T2DM who satisfy any or all of the following:C-peptide positive, but with suboptimal control on a

maximal program of basal/bolus injections Substantial dawn phenomenonErratic lifestyle (e.g., unpredictable schedules leading to

difficulty maintaining meal timing)Severe insulin resistance, candidate for U500 insulin by

CSIIAlso, selected patients with other types of diabetes

mellitus (e.g., post-pancreatectomy)T2DM: type 2 diabetes mellitus

CSII: continuous subcutaneous insulin infusion

Insulin Pump Provider Selection

Insulin Pump Provider SelectionAbout 2000 US physicians prescribe insulin pumps Only providers whose practice can assume full

responsibility for a comprehensive pump management program should offer the technology

The availability of adequate patient education, training, and follow-up is essential to ensure optimal use of this technology

Providers should conduct periodic audits of pump settings in the context of current glucose dynamics

Skyler JS, et al. Clinical Diabetes. 2007(25):50-56Chait J. http://www.diabetesselfmanagement.com/articles/insulin/insulin_pumps/1/. April 2013

Insulin Pump Use in Various Patient Populations

Adult Patients (1)Before therapeutic initiation, the patient should

have a multidisciplinary CSII health care team in place

The health care team should develop a comprehensive education and training plan, including information on:Insulin pump and infusion set operation Maintenance and troubleshooting Infusion site preparation The calculation and configuration of basal insulin

infusion rates, initial insulin-carbohydrate ratios, boluses, and insulin sensitivity factor

CSII: continuous subcutaneous insulin infusion

Adult Patients (2) At CSII initiation, the patient should have

daily contact with the pump trainerA return visit with the

endocrinologist/diabetologist within 3 to 7 days of initiation is advised

Educational consults should be scheduled weekly or biweekly at first, then periodically as needed

Specialist follow-up visits should be scheduled at least monthly until the pump regimen is stabilized, then at least once every 3 months

CSII: continuous subcutaneous insulin infusion

Pediatric PatientsPediatric diabetes specialists agree that CSII is indicated

for pediatric patients with: Elevated HbA1c levels on injection therapy

Frequent, severe hypoglycemia

Widely fluctuating glucose levels

A treatment regimen that compromises lifestyle

Microvascular complications and/or microvascular risk factors

Ideal pediatric candidates have motivated families, with a working understanding of diabetes management, and committed to monitoring blood glucose ≥ 4 times/day

Patient age and duration of diabetes should not be factors in determining the transition from injections to CSII

CSII: continuous subcutaneous insulin infusion Phillip M, et al. Diabetes Care. 2007;30(6):1653-1662

Method 1.Pre-Pump Total

Daily Dose (TDD)

Pre-Pump TDD x .75

Method 2.Patient Weight

Wt kg x .5 or lb x .23

Pump TDD

Calculations for Insulin Pump Settings

Basal Rate

(Pump TDD x .5) / 2- h

Sensitivity Factor / Correction

1700 / Pump TDD

-Start with 1 basal rate, adjust according to glucose trends over 2-3 days-Adjust to maintain stability in fasting state (between meals & during sleep)-Add additional basals according to diurnal variation (dawn phenomenon)

Carb Ratio

450 / TDD

-Adjust based on low-fat meals with known carbohydrate content-Acceptable 2-h post-prandial rise is ~60mg/dL above pre-prandial BG-Adjust carb ratio in 10%-20% increments based on post-prandial BG ALTERNATE METHODS-Carb Ratio: (6x Wt in kg / TDD) or (2.8 x Wt in lbs / TDD)-Fixed Meal Bolus = (TDD x .5) / 3 equal meals (not carb counting)

-Sensitivity Factor is correct if BG is within 30 mg/dL of target range within 2 hours after correction -Make adjustments in 10%-20% increments if 2-hr post- correction BGs are consistently above or below target

Clinical Considerations on Pump TDD-Average values from Method 1 & 2-Hypoglycemic patients start at lower value-Hyperglycemic, elevated A1C, or pregnant start at higher value

Clinical Guidelines

TDD: total daily doseBG: blood glucose

Pregnant Women with Diabetes – T1DMInsulin pump therapy has not been shown to be

superior to MDI for maintaining HbA1c levels in pregnant women

A 2007 Cochrane review analyzed 5 randomized controlled trials comparing CSII with MDI in pregnant women with diabetes; no significant differences were found in any outcomes measured

Overall, the literature does not provide clear evidence that CSII is necessary for optimal treatment of women with T1DM during pregnancy

MDI: multiple daily injectionCSII: continuous subcutaneous insulin infusion

T1DM: type 1 diabetes mellitusCohen O, et al. Gynecol Endocrinol. 2008;24(11):611-613.Farrar D, et al. Cochrane Database Syst Rev. 2007;(3)(3):CD005542

Pregnant Women with Diabetes – T2DM and GDMResearch is limited on pregnant women

with T2DMHowever, insulin pump therapy seems to

be safe and effective for maintaining glycemic control in pregnancies complicated by GDM/T2DM and requiring large insulin doses

During pregnancy, intensive education and surveillance of the infusion site and sets are required

T2DM: type 2 diabetes mellitusCSII: continuous subcutaneous insulin infusion

GDM: gestational diabetes mellitusSimmons D, et al. Diabetes Care. 2001;24(12):2078-2082

Insulin infusion rates for women with T1DM:

Total basal insulin requirement for 24 hours

Gestation Units × Weight (in kg)

Pre-pregnancy 0.3

First trimester 0.35

Second trimester 0.4

Third trimester 0.45

Term pregnancy (>38 weeks’ gestation)

0.5

Suggested Protocol for Insulin Pump Use During Pregnancy Hourly infusion rate changes based on time

of day(divide the total basal units by 24)

Time of Day Infusion Rate

12-4 AM ½ calculated basal rate

4-10 AM 1½ calculated basal rate

10 AM - 6 PM Calculated (may need adjustment based on stress & exercise in the time period)

6 PM – 12 AM

Calculated (may need adjustment based on stress & exercise in the time period)

Meal-related insulin bolus*

GestationUnits × Weight (in kg)(divided into thirds for a dose before each meal)

Pre-pregnancy 0.3

First trimester 0.35

Second trimester 0.4

Third trimester 0.45

Term pregnancy (>38 weeks’ gestation)

0.5

After second trimester, in case of dislodgment at infusion site

Dose of NPH 0.1 × weight (in kg) before bed; then lower early morning insulin infusion rate

* Use only rapid-acting insulin analogues

T1DM: type 1 diabetes mellitus

Insulin Pumps in Inpatient SettingsWhen CSII users are evaluated for a non-acute hyper-

or hypoglycemic crisis, they typically have more insulin pump knowledge and expertise than the medical professionals handling their hospital stay

At emergency room or hospital admission, the specialist(s) responsible for the patient’s ambulatory pump management should be contacted promptly to make decisions about infusion adjustments

Patients should be instructed to not discontinue the pump infusion, unless directed by their diabetes specialist

CSII: continuous subcutaneous insulin infusion

Using U-500 Insulin in a Pump Several studies have shown that

concentrated regular (R) U-500 insulin delivered by CSII is safe and effective

Although R U-500 insulin is not FDA-approved for use in CSII, this treatment appears to be effective in delivering insulin to patients with T2DM who have high insulin requirements and are failing other treatment regimens

CSII: continuous subcutaneous insulin infusion FDA: U.S. Food and Drug Administration

T2DM: type 2 diabetes mellitus

Knee TS , et al. Endocr Pract. 2003;9(3):181-186. Schwartz FL. Endocr Pract. 2004;10(2):163-164. Lane WS. Endocr Pract. 2006;12(3):251-256.Bulchandani DG, et al. Endocr Pract. 2007;13(7):721-725.Reutrakul S, et al. J Diabetes Sci Technol. 2011;5(4):1025-1026. Lane WS. Endocr Pract. 2010;16(5):778-784. ClinicalTrials.gov. http://clinicaltrials.gov/show/NCT01774968 November 2013.

Insulin Pump Training

Insulin Pump TrainingTraining patients on insulin pump use is

necessary to reduce the risk of adverse events

Patient diabetes education and pump training should be implemented by a multidisciplinary team under the direction of an experienced endocrinologist/diabetologist

The health care team should periodically reevaluate whether pump therapy is appropriate for the patient

Developing Uniform TrainingAn introduction to insulin pump therapy should

include: A description of the different devices available and

a demonstration of the benefits of eachThe technical aspects of using the deviceChoice of infusion sets and their correct use Preventing infusion site and infection site reactions

Patients should be taught: The meaning of pump alarmsTo keep backup supplies on handTo make recommended pump setting changes at

home

Training Patients and Their FamiliesPatients and their families should:

Be provided with a written summary of responses to different emergency situations

Have periodic skills retesting to maximize the effectiveness of pump therapy and maintain safety

Be re-trained when switching to a new pump model

Be periodically reminded of the manufacturer’s emergency number

Patient Safety Issues

Patient Safety IssuesUsability and human factors should be used

as criteria to judge new insulin pumps Every patient using an insulin pump should

have an experienced, pump-knowledgeable diabetes care team

All patients should have periodic re-education and re-training to address knowledge gaps

Patient suitability for pump use must be re-examined over a patient’s lifetime

Coding and Reimbursement

Coding for CSII

Code Typical Timefor Code

Threshold Time to Bill Code 99354

(min)

99203 30 60

99204 45 75

99205 60 90

99213 15 45

99214 25 55

99215 40 70

Payment for existing codes for diabetes education has not been established across the private and public sectors

Existing evaluation and management (E/M) codes for office encounters are used

These involve initial or follow-up use (dependent on the complexity of the visit)

If the physician time involved exceeds appropriate visit time, use prolonged visit codes

CSII: continuous subcutaneous insulin infusion

Reimbursement

CMS also covers CSII, contingent upon certain criteria:• Patient must be insulinopenic, defined as having a fasting C-peptide level ≤110% of the laboratory’s lower limit of normal, with a concurrently obtained fasting glucose ≤225 mg/dL

• Or patient must be β-cell autoantibody-positive

Most private insurers provide reimbursement

for insulin pumps for patients with T1DM and

T2DM, as well as for qualified insulin-

dependent diabetes patients, without regard

to diabetes type

T1DM: type 1 diabetes mellitusT2DM: type 2 diabetes mellitus

CMS: Centers for Medicare and Medicaid Services CSII: continuous subcutaneous insulin infusion CMS. https://www.cms.gov/manuals/iom/list.asp. 2010

Centers for Medicare & Medicaid Services (CMS) Insulin Pump Reimbursement RequirementsA. Patient has completed a comprehensive diabetes education

program and has been receiving MDI insulin with frequent self-adjustments for at least 6 months before pump initiation. Patient has documented SMBG frequency an average of ≥4 times per day during the previous 2 months. Patient must also meet ≥1 of the following criteria HbA1c >7.0% History of recurrent hypoglycemia Wide fluctuations in blood glucose before mealtime Dawn phenomenon with FPG frequently >200 mg/dL, or a history of

severe glycemic excursions

B. Patient on pump therapy before enrollment and has documented SMBG an average of ≥4 times per day during the month before enrollment

C. Fasting C-peptide ≤110% lower limit of normal or ≤200% lower limit of normal if CrCl ≤50 ml/min with concurrent FPG ≤225 mg/dL; or beta-cell autoantibody positive (+ICA or GAD antibodies)

CrCl, creatinine clearance; FPG, fasting plasma glucose; GAD, glutamate decarboxylase, HbA1c, hemoglobin A1c; ICA, islet cell antibodies; MDI, multiple daily injections; SMBG, self-monitored blood glucose

CMS. https://www.cms.gov/manuals/iom/list.asp. 2010

Health Economics of Insulin Pump Therapy

Cost-effectiveness Analyses Comparing CSII vs. MDI in Patients with T1DM and T2DM Several studies have found that CSII is either cost-

saving or cost-effective vs. MDI1-3

Research also indicates that CSII represents a good value for cost4-6

One study found that reduced insulin and drug‐related expenditures offset initial CSII investment within 3 years for the most costly insulin users7

Another study found that SAPT, in its currently state of development, was not economically attractive in the US for adults with T1DM8

1) St. Charles et al, Value Health. 2009;12(5):674-686. 2) St. Charles et al, Clin Ther. 2009;31(3):657-667. 3) Cummins et al, Health Technol Assess. 2010;14(11):1-181. 4) Nørgaard K, et al, Ugeskr Laeger. 2010;172(27):2020-2025. 5) Cohen N et al, Pharmacoeconomics. 2007;25(10):881-897. 6) Roze et al, Diabet Med. 2005;22(9):1239-1245. 7) David G, et al, Value Health 2012;15(4):A65. 8) Kamble S, et al, Value Health. 2012;15(5):632-638.

CSII: continuous subcutaneous insulin infusion MDI: multiple daily injection

T1DM: type 1 diabetes mellitus T2DM: type 2 diabetes mellitus

SAPT: sensor-augmented pump therapy

Future Needs and Conclusions

Future Needs and ConclusionsFurther enhancements are needed to improve

the configurability and safety of insulin pumps There is a clear need for educational programs

to provide patients with initial and follow-up training

Research continues on an “artificial pancreas” that can dose the correct amount of insulin at the right time

Peer reviewed research studies must continue to be conducted and research findings need to be translated for use in clinical practice