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AHRQ’s Effective Health Care Program: Applying Existing Evidence to Diabetes Care

Slide Presentation in Text Format

Tuesday, December 14, 2010

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  • On the top of the slide are the logos for the U.S. Department of Health and Human Services and the Agency for Healthcare Research and Quality (AHRQ).

 

Slide 2

Questions

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CALL-IN NUMBER: (888) 632-5065 ACCESS CODE: 25848872#


Slide 3

Agenda

  • Brief Overview of Patient-Centered Outcomes Research and AHRQ’s Effective Health Care Program - Sonia Nagda, moderator
  • Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes - Rehan Qayyum, M.D., M.H.S.
  • Q&A from Audience

 

CALL-IN NUMBER: (888) 632-5065 ACCESS CODE: 25848872#

 

Slide 4

Questions

To submit a question:

  • Press the “Ask Question” button located at the bottom of the screen.
  • When you click on the button, a box will appear at the bottom of your screen requesting that you enter your question.
  • Once completed, press the “Submit” button.


Slide 5

Patient-Centered Outcomes Research and AHRQ’s Effective Health Care Program

Sonia Nagda, M.D., M.P.H.
AHRQ’s Office of Communications and Knowledge Transfer


Slide 6

Patient-Centered Outcomes Research

  • Also known as comparative effectiveness research

 

  • Unbiased and practical, evidence-based information
  • Compares drugs, devices, tests and surgeries, and approaches to health care
    • Benefits and harms
    • What is known and what isn’t

 

  • Descriptive, not prescriptive


Slide 7

A Framework for Patient-Centered Outcomes Research

This framework outlines the step-by-step process for how the development and implementation of patient-centered outcomes research leads to improvement in health care. Once a topic is nominated, a horizon scan and synthesis of the evidence is completed, followed by evidence generation. Then the research is translated, disseminated and implemented.


Slide 8

Research Focus: 14 Priority Conditions

  • Arthritis and nontraumatic joint disorders
  • Cancer
  • Cardiovascular disease, including stroke and hypertension
  • Dementia, including Alzheimer’s disease
  • Depression and other mental health disorders
  • Developmental delays, ADHD and autism
  • Diabetes mellitus
  • Functional limitations and disability
  • Infectious disease including HIV/AIDS
  • Obesity
  • Peptic ulcer disease and dyspepsia
  • Pregnancy including preterm birth
  • Pulmonary disease/asthma
  • Substance abuse

Slide 9

Effective Health Care Program Translation Products

Multiple images of different products that the Effective Health Care Program creates from the systematic review reports. These products include: CE modules, interactive case studies, faculty slides, patient decision aid, policymaker summary, consumer guide, clinician guide, Web site, and executive summary.


Slide 10

Diabetes Resources

Two images of consumer guides titled, Gestational Diabetes: A Guide for Pregnant Women and Premixed Insulin for Type 2 Diabetes: A Guide for Adults.


Slide 11

Public Involvement

This slide shows multiple images of what must be done during the research process in order to disseminate the findings in multiple ways. The research process includes: topic generation, topic development, topic refinement, research review, and research needs and development. The multiple ways that information is disseminated includes: Web links, newsletter blurbs, articles or comment, Web conferences, and continuing education.


Slide 12

Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults with Type 2 Diabetes

Rehan Qayyum, M.D., M.H.S.

Prepared for: Agency for Healthcare Research and Quality
Contract No.: #290-02-0018
Prepared by: Evidence-based Practice Center, The Johns Hopkins University

 

Slide 13

Insulin Analogues

  • Insulin analogues are altered forms of human insulin with minor structural changes without affecting glycemic control.
  • These structural changes impart pharmacokinetic properties that allow better control of the onset and duration of insulinlike activity.
  • These analogues are produced using recombinant DNA technology.

 

Slide 14

Insulin Analogues

The slide has a simplified diagram of two rapid-acting insulin analogues. These two molecules are included in premixed insulin analogue preparations available. In the upper half of the figure there is the structure of insulin aspart where proline adds at position 28 and where B chain insulin molecule is then replaced by aspartic acid. The lower half of the figure shows a structure of insulin proline. In this analogue the positions of two adjacent amino acids on B chain are switched. The lysine amino acid at position 29 is replaced by proline, and proline at position 28 is replaced by lysine.


Slide 15

Premixed Insulin Analogues

  • Mixture of rapid-acting and intermediate-acting insulin analogues
  • Intermediate-acting insulin is prepared by mixing insulin analogues with protamine sulfate

 

Slide 16

Key Questions

 

  1. In adults (age ≥ 18 years) with type 2 diabetes, what is the effectiveness of premixed insulin analogues (insulin aspart 70/30, insulin lispro 75/25, insulin lispro 50/50) in achieving optimal glycemic control, as compared to insulin regimens including, but not necessarily limited to, the following preparations?
    • Premixed human insulin preparations (neutral protamine Hagedorn [NPH]/regular 70/30, NPH/regular 50/50)
    • Long-acting insulin analogues (insulin detemir, insulin glargine) administered alone
    • Intermediate-acting human insulin (NPH insulin) administered alone
    • Short-acting human insulin (regular insulin) administered prandially
    • Rapid-acting insulin analogues (insulin aspart, insulin glulisine, insulin lispro) administered separately (prandially) with a long-acting insulin analogue (insulin detemir, insulin glargine)
  2. For adults with type 2 diabetes, do premixed insulin analogues differ from other commonly used insulin preparations with regard to safety, adverse effects, or adherence? The adverse effects of interest include, but are not limited to, hypoglycemia (nocturnal and daytime), weight gain, and interactions with other medications.

 

Slide 17

Key Questions (cont.)

  1. Does the effectiveness or safety of the new premixed insulin analogue regimens vary across the following subpopulations of patients with type 2 diabetes
    • The elderly (≥ 65 years), very elderly (≥ 85 years)
    • Other demographic groups (ethnic or racial groups, genders)
    • Individuals with comorbid medical conditions
    • Individuals with limited life expectancy
    • Individuals with disabilities
  2. What is the effectiveness and safety of the new premixed insulin analogue regimens in individuals on oral antidiabetic agents and individuals with different blood glucose patterns (such as fasting hyperglycemia or postprandial hyperglycemia) or types of control (such as tight control, usual control, good fasting or postprandial control)?


Slide 18

Methods

  • Search Strategy
    • Electronic database (February 2008)
    • Hand search of literature and Web sites
    • Scientific information submitted by the pharmacy industry
  • Study Inclusion Criteria
    • Clinical trials and observational studies
      • Two reviewers independently selected studies
  • Data Abstraction
    • For relevant outcomes
    • Crossover studies excluded from progressive outcomes

 

 

Slide 19

Statistical Methods

  • Intermediate outcomes (Fasting and postprandial glucose, A1c)
    • Random effects model
  • Adverse Effects (Hypoglycemia, weight change)
    • Random effects model
  • Clinical Outcomes (rare-event data)
    • Fixed effects model (Mantel-Haenszel)
    • Sensitivity analysis with Peto’s method and Bayesian random-effects model

 

Slide 20

Results

Reasons for Exclusion (576) at the Abstract Review Level*
Did not apply to a key question: 158
Not in English: 67
Did not apply to humans: 1
Did not contain original data: 253
Did not compare an FDA-approved premixed insulin analogue: 154
Did not address type 2 diabetic patients: 38
Did not evaluate adults (age 18+): 3
Did not evaluate an FDA-approved premixed insulin analogue: 302
Other: 10

Reasons for Exclusion (88) at the Article Review Level*
Did not apply to key question: 8
Not in English: 5
Did not apply to humans: 0
Did not contain original data: 46
Did not compare an FDA-approved premixed insulin analogue: 14
Did not address type 2 diabetic patients: 3
Did not evaluate adults (age 18+): 0
Did not evaluate an FDA-approved premixed insulin analogue: 23
Other: 12

Qayyum et al. Ann Intern Med. 2008; 21:549-559


Slide 21

Results
-Fasting Glucose-

This slide shows a pooled assembly of results on the comparative effect of premixed insulin analogues on fasting glucose. At the bottom of this figure it is divided into three parts where each part provides a comparison. Horizontally the middle section is a pictorial representation of the pooled results. The black squares represent mean values and black lines on each side of the square represent 95 percent confidence intervals. The vertical line in the center represents no change in fasting glucose. There is no statistically significant difference if the line is 95 percent confidence interval cross the vertical line. Overall the data on this chart shows premixed insulin analogues were inferior to long-acting insulin analogues that were similar to premixed human insulin preparations and superior to noninsulin antidiabetic agents.


Slide 22

Results
-Postprandial Glucose-

This slide shows the comparative effect of premixed insulin analogues on postprandial glucose. The organization of this figure is similar to the previous slide. This slide shows clearly a superiority of premixed insulin analogues over the other three groups, which is different from what is shown on slide 21. At an average, premixed insulin analogs decreased postprandial glucose an additional 28 milligram per deciliter in comparison to long acting insulin analogs. An additional 19 milligram per deciliter in comparison to premixed human insulin preparations and 37 milligram per deciliter at an average in comparison to noninsulin antidiabetic agents. Overall the data on this chart shows if one watched their target postprandial hyperglycemia premixed insulin analogs offer a better choice in comparison to the three groups shown on the chart. This conclusion is different than slide 21 which showed that long acting insulin analogs are better for fasting glycemic control.


Slide 23

Results
-Hemoglobin A1C-

This slide shows data of hemoglobin A1C, which is the most important clinical parameter focused on by clinicians. This parameter incorporates both fasting and postprandial glycemic control. When comparing long acting insulin analogs, premixed insulin analogs were better and were able to decrease A1C by an additional 0.4 percent. However there was no difference between premixed human insulin when compared with premixed insulin analogs. Both of these groups were very similar in being able to decrease hemoglobin A1C.


Slide 24

Results
-Hypoglycemia-

This slide shows data of hyperglycemia and is slightly different from the previous slides because instead of having individual premixed insulin analogs listed, hypoglycemia is further categorized. Overall long acting insulin analogs appear safer than premixed insulin analogs. Long acting insulin analogs are safer for hyperglycemia without a specified severity and for symptom only hyperglycemia. The chart shows a trend towards less hyperglycemia with long acting insulin analogs.


Slide 25

Results
-Weight Change-

  Mean 95 % CI P-value
Long-acting insulin analogues vs. All premixed insulin analogues 1.97 1.22 to 2.73 < 0.001
Insulin Aspart 70/30 2.5 1.6 to 3.4 < 0.001
Insulin Lispro 75/25 No data
Insulin Lispro 50/50 1.58 0.99 to 2.18 < 0.001
Noninsulin antidiabetic agents vs. All premixed insulin analogues 2.35 0.84 to 3.86 0.002
Insulin Aspart 70/30 2.82 0.61 to 5.02 0.012
Insulin Lispro 75/25 1.88 1.35 to 2.41 < 0.001
Insulin Lispro 50/50 No data
Premixed Human insulin vs. All premixed insulin analogues Not enough data

Slide 26

Results
-Other Comparisons-

No or scant data for other comparisons


Slide 27

Results
-Clinical Outcomes-

This slide shows a chart of clinical outcomes. The chart shows there is harm in pooled ratios for all cause mortality for cardiovascular mortality and the combined outcome of cardiovascular morbidity and mortality when premixed insulin analogs were compared to other antidiabetic medications.


Slide 28

Results
-Quality of Life-

  • Six studies evaluated this outcome.
  • In four studies using validated measurement tools, only one of six quality of life outcomes (psychological distress) showed a statistically significant difference, in favor of premixed insulin analogues over other antidiabetic agents.

Slide 29

Results
-in combination with oral agents-

  • Fasting glucose, Postprandial glucose, and Hypoglycemia
    • 3 studies; no significant difference
  • Hemoglobin A1c
    • 3 studies, combination better than premixed analogues alone
  • Weight change and Clinical outcomes
    • 2 studies, no significant difference

 

Slide 30

Results

  • No evidence for
    • adherence to treatment regimen
    • effectiveness and safety in subpopulations of interest
    • different intensity of glucose control
    • targeting fasting versus postprandial glucose control

 

Slide 31

Case Study 1

  • 50-year-old obese diabetic male comes in for his regular clinic visit
    • HbA1C = 8.7
    • Fasting glucose = 160-190
    • On glipizide 10 mg twice daily and metformin XL 1000mg twice daily



Slide 32

Case Study 2

  • 56-year-old diabetic female comes in for her regular clinic visit
    • HbA1C = 7.4
    • Fasting glucose = 120-140
    • Postprandial glucose = 180-220
    • On glyburide/metformin 5/500 BID and sitagliptin 100mg QD

Slide 33

Summary

This chart shows a summary of different variables and how the variables changes with a premixed analogue versus comparator.

 

Slide 34

Questions

To submit a question:

  • Press the “Ask Question” button located at the bottom of the screen.
  • When you click on the button, a box will appear at the bottom of your screen requesting that you enter your question.
  • Once completed, press the “Submit” button.

                                                                                      
Slide 35

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Slide 36

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