Insulin Pump Management

Consensus 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, ECNU Bruce W. Bode, MD, FACE Yehuda Handelsman, MD, FACP, FACE, FNLA Richard Hellman, MD, FACP, FACE Lois Jovanovič, MD, MACE Wendy S. Lane, MD Philip Raskin, MD, FACE William V. Tamborlane, MD

ENDOCRINE PRACTICE: TBD

Presentation Outline

           Introduction Preamble State of Insulin Pump Technology Clinical Evidence Patient and Provider Selection Insulin Pump Use in Various Patient Populations Education and Training Patient Safety Issues Coding and Reimbursement Issues in Practice Economics of Insulin Pump Therapy Future Needs and Conclusions

Introduction



Introduction

First AACE consensus statement on insulin pump management published in 2010  Current consensus statement includes:  Extensive updates on state of insulin pump technology  Expanded discussion of CSII in pediatric patients  Data on use of concentrated regular U-500 insulin in CSII  Discussion on need to develop uniform training  Suggestions of what uniform training should cover  Discussion of device-related pump problems  Impact of patient selection and education on safe CSII use AACE: American Association of Clinical Endocrinologists CSII: 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. 2010 U.S. CDC. CDC Media Relations - Press Release: October 22, 2010.

T1DM: type 1 diabetes mellitus T2DM: type 2 diabetes mellitus FDA: U.S. Food and Drug Administration CSII: continuous subcutaneous insulin infusion

State of Insulin Pump Technology

State of Insulin Pump Technology

 Insulin pumps now include features such as  Color touch screens  USB-rechargeable batteries  Pre-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 Technology

 Clinical 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

Insulin Pumps on the Market

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 Disposable Insulin Delivery Device Roche Health Solutions Asante Solutions Medtronic MiniMed Medtronic MiniMed Insulet Corporation Animas Tandem Diabetes Care Valeritas, Inc.

Clinical Evidence for Insulin Pump Therapy in Diabetes

Type 1 Diabetes

 A 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 HbA 1c response, favoring CSII  CSII users demonstrated greater improvements in quality of life measures  Severe hypoglycemia appeared to be reduced in CSII users Misso ML, et al. Cochrane Database Syst Rev. 2010;(1):CD005103. doi(1):CD005103 CSII: continuous subcutaneous insulin infusion MDI: multiple daily injection T1DM: type 1 diabetes mellitus

Type 1 Diabetes

 The STAR-3 study showed significantly greater HbA 1c reductions in patients with T1DM randomly assigned to sensor-augmented insulin pump therapy vs. MDI  A higher proportion of patients randomly assigned to pump therapy achieved an HbA 1c <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 Reduction T1DM: type 1 diabetes mellitus MDI: multiple daily injection CSII: 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 HbA 1c and mean blood glucose decreases

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

HbA 1c 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, HbA 1c 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

HbA 1c was lower for CSII than for MDI, with greatest improvement in patients with highest initial HbA 1c 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

HbA 1c was significantly lower with CSII vs. MDI; HbA and MDI therapy 1c reduction was only evident for studies with mean patient age >10 years; severe hypoglycemia occurred at comparable rates with CSII

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

Type 2 Diabetes

 Fewer clinical investigations have examined CSII in patients with T2DM  In an analysis of four randomized controlled trials involving patients with T2DM:  No significant HbA 1c improvements, differences in hypoglycemic risk, or weight differences were observed with CSII vs. MDI over 12 to 52 weeks Bode BW. Diabetes Technol Ther. 2010;12 Suppl 1:S17-21. CSII: continuous subcutaneous insulin infusion T2DM: type 2 diabetes mellitus MDI: multiple daily injection

Randomized Clinical Trials Comparing CSII and MDI for Patients With T2DM

HbA 1c (%) Reference

Noh et al, Diabetes Metab Res Rev. 2008;24(5):384-391. Parkner et al, Diabetes Obes Metab. 2008;10(7):556-563. Berthe et al, Horm Metab Res. 2007;39(3):224-229. Herman et al, Diabetes Care. 2005;28(7):1568-1573. Raskin et al, Diabetes Care. 2003;26(9):2598-2603 Wainstein et al, Diabet Med. 2005;22(8):1037-1046.

Design Baseline

30-week observational study (N=15) 7.9

Observational study, 3 successive nights (N=10) Crossover study, 2 12-week periods (N=17) 1 year parallel study (N=107) Fasting plasma glucose: 209 mg/dL 9.0

24 week parallel study (N=132) Crossover study, 2 18-week periods (N=40) CSII: 8.4

MDI: 8.1

CSII: 8.2

MDI: 8.0

CSII-MDI: 10.1

MDI-CSII 10.2

5.0

CSII

NA

MDI P-value

<0.001

99.1 mg/dL 7.7

6.6

7.6

−0.8

NA 8.6

6.4

7.5

+0.4

<0.0001

<0.03

0.19

NS 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 Candidate

 The 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 control  Willing 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 mellitus T2DM: 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 injection SMBG: self-monitored blood glucose

Proposed Clinical Characteristics of Suitable Insulin Pump Candidates – T1DM Patients

 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 unawareness Significant “dawn phenomenon,” extreme insulin sensitivity   Patients with T1DM who feel that CSII would be helpful in managing their diabetes Special populations (e.g., preconception, pregnancy, children, adolescents, competitive athletes) T1DM: type 1 diabetes mellitus MDI: multiple daily injection CSII: continuous subcutaneous insulin infusion

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 phenomenon Erratic lifestyle (e.g., unpredictable schedules leading to difficulty maintaining meal timing)  Severe insulin resistance, candidate for U500 insulin by CSII Also, 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 Selection

 About 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):50-56 Chait 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 trainer  A 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 Patients

 Pediatric diabetes specialists agree that CSII is indicated for pediatric patients with:   Elevated HbA 1c 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 Phillip M, et al. Diabetes Care. 2007;30(6):1653-1662 CSII: continuous subcutaneous insulin infusion

Calculations for Insulin Pump Settings

Clinical Guidelines

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

Basal Rate

(Pump TDD x .5) / 2- h

Carb Ratio

450 / TDD

Sensitivity Factor / Correction

1700 / Pump TDD

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 -

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) -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

TDD: total daily dose BG: blood glucose

Pregnant Women with Diabetes – T1DM

 Insulin pump therapy has not been shown to be superior to MDI for maintaining HbA 1c pregnant women levels in  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 Cohen O, et al. Gynecol Endocrinol. 2008;24(11):611-613.

Farrar D, et al. Cochrane Database Syst Rev. 2007;(3)(3):CD005542 MDI: multiple daily injection CSII: continuous subcutaneous insulin infusion T1DM: type 1 diabetes mellitus

Pregnant Women with Diabetes – T2DM and GDM



Research is limited on pregnant women with T2DM



However, 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 mellitus CSII: continuous subcutaneous insulin infusion GDM: gestational diabetes mellitus Simmons D, et al. Diabetes Care. 2001;24(12):2078-2082

Suggested Protocol for Insulin Pump Use During Pregnancy

Insulin infusion rates for women with T1DM: Total basal insulin requirement for 24 hours Gestation Units × Weight (in kg)

Pre-pregnancy First trimester Second trimester Third trimester Term pregnancy (>38 weeks’ gestation) 0.3

0.35

0.4

0.45

0.5

Hourly infusion rate changes based on time of day (divide the total basal units by 24) Time of Day

12-4 AM 4-10 AM 10 AM - 6 PM

Infusion Rate

½ calculated basal rate 1½ calculated basal rate 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* 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

Gestation

Pre-pregnancy First trimester Second trimester Third trimester Term pregnancy (>38 weeks’ gestation)

Units × Weight (in kg)

(divided into thirds for a dose before each meal) 0.3

0.35

0.4

0.45

0.5

* Use only rapid-acting insulin analogues T1DM: type 1 diabetes mellitus

Insulin Pumps in Inpatient Settings

 When 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 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.

CSII: continuous subcutaneous insulin infusion FDA: U.S. Food and Drug Administration T2DM: type 2 diabetes mellitus

Insulin Pump Training

Insulin Pump Training

 Training 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 Training

 An introduction to insulin pump therapy should include:  A description of the different devices available and a demonstration of the benefits of each   The technical aspects of using the device Choice of infusion sets and their correct use  Preventing infusion site and infection site reactions  Patients should be taught:   The meaning of pump alarms To keep backup supplies on hand  To make recommended pump setting changes at home

Training Patients and Their Families

 Patients 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 Issues

 Usability 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

99203 99204 99205 99213 99214 99215

Typical Time for Code

30 45 60 15 25 40

Threshold Time to Bill Code 99354 (min)

60 75 90 45 55 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

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 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

CMS. https://www.cms.gov/manuals/iom/list.asp. 2010 T1DM: type 1 diabetes mellitus T2DM: type 2 diabetes mellitus CMS: Centers for Medicare and Medicaid Services CSII: continuous subcutaneous insulin infusion

Centers for Medicare & Medicaid Services (CMS) Insulin Pump Reimbursement Requirements

A.

B.

C.

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   HbA 1c >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 Patient on pump therapy before enrollment and has documented SMBG an average of ≥4 times per day during the month before enrollment 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) CMS. https://www.cms.gov/manuals/iom/list.asp. 2010 CrCl, creatinine clearance; FPG, fasting plasma glucose; GAD, glutamate decarboxylase, HbA 1c , hemoglobin A 1c ; ICA, islet cell antibodies; MDI, multiple daily injections; SMBG, self-monitored blood glucose

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. MDI 1-3 Research also indicates that CSII represents a good value for cost 4-6   One study found that reduced insulin and drug‐related expenditures offset initial CSII investment within 3 years for the most costly insulin users 7 Another study found that SAPT, in its currently state of development, was not economically attractive in the US for adults with T1DM 8 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 Conclusions

 Further 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