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CompletedNCT02911818MODELUpdated May 7, 2019Results posted

Lifestyle Modification and Liraglutide

A Phase 4 interventional study of CMS-recommended lifestyle counseling and Liraglutide 3.0mg in Obesity, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 21 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-05-07.

Sponsored by University of Pennsylvania · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
21 Years to 70 Years
Sex
All
01

Study summary

This is a 52 week, single center, open-labeled, randomized controlled trial.

A total of 150 subjects with obesity, who are free of types 1 and 2 diabetes, as well as contraindications to weight loss, will be randomly assigned to one of three treatment groups: 1) lifestyle counseling, as currently recommended by the Centers for Medicare and Medicaid Services (CMS) (i.e., CMS-Alone); 2) CMS lifestyle counseling plus liraglutide (i.e., CMS-Liraglutide); or 3) CMS-Liraglutide plus a portion-controlled diet (i.e., Multi-Component Intervention).

Subjects in all three groups will have 14 brief (15 minute) lifestyle counseling visits the first 24 weeks, followed by monthly visits in weeks 25-52. This is the schedule and duration of counseling visits recommended by CMS. Counseling sessions will be delivered by a physician, nurse practitioner or registered dietitian (RD) working in consultation with the former providers.

Subjects in all three groups also will have brief physician visits at weeks 1, 4, 8, 16, 24, 36, and 52 (total of 7 visits). These visits are needed for subjects in both liraglutide groups to monitor their response to the medication. These visits are included for subjects in CMS-Alone to match the intensity of medical care provided the two other groups.

The primary outcome is % reduction in initial body weight, as measured from randomization to week 52. Secondary outcomes include the proportion of participants who at week 52 lose >5%, >10%, and >15% of initial weight, as well as % reduction in weight at week 24 and the proportion of participants who meet the three categorical weight losses at this time. The secondary efficacy measures include changes (from randomization to week 52) in cardiovascular disease (CVD) risk factors, glycemic control, mood, quality of life, eating behavior, appetite, sleep, and satisfaction with weight loss.

Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).

Statistical Analysis. Using a sample size equation for longitudinal clustered samples, a randomization sample of 50 subjects in CMS-Alone, 50 in CMS-Liraglutide, and 50 in the Multi-Component Intervention provides >80% power to detect the two primary contrasts to be statistically significant. This estimate allows for 20% attrition during the 52-week trial, resulting in approximately 40 treatment completers per group. The ITT longitudinal statistical design will further improve power by allowing the inclusion of available data for non-completers and the adjustment of possible variance reducing baseline covariates.

Read the detailed description

The addendum to the original 52-week trial, is a 12-week, single center, randomized placebo-controlled, parallel group designed trial. This 12-week extension study is separate from the original 52-week trial and will not affect the outcome or analysis of the 52-week, 3-arm trial.

Participants and investigators will be masked to participants' assignment to phentermine 15 mg/d versus placebo. Participants in both groups will receive liraglutide in an open-label manner.

We anticipate that 23 (of 50) participants from the original CMS-Liraglutide group and 23 (of 50) from the Multi-Component Intervention will be eligible to participate in the extension study and will elect to do so. We anticipate that 20 participants in each group will complete the 12-week extension study and that those who receive liraglutide 3.0 mg plus phentermine 15.0 mg/d will lose, from randomization to week 12, 3.5+3.5% of initial weight, compared with 0.0+0.5% for those assigned to liraglutide plus placebo.

All participants in the extension study will meet with a physician or nurse practitioner at randomization (week 0) and at weeks 2, 4, 8 and 12. On each occasion they will review patients' blood pressure and pulse, assess suicidal ideation, and record and respond appropriately to reports of changes in physical health. As during the 1-year prior trial, brief lifestyle counseling (15 min) will provided at monthly visits (excluding week 2) by the physician or nurse practitioner or by a registered dietitian or behavioral psychologist, working under their supervision. The lifestyle intervention will be the same as that provided during the last 6 months of both the CMS-Liraglutide and Multi-Component interventions.

Following the 12-week randomized trial, phentermine (or placebo) will be terminated, and all participants will continue to receive liraglutide 3.0 mg/d for an additional 8 weeks (i.e., weeks 12-20) and have lifestyle counseling and medical assessments at weeks 16 and 20. Liraglutide 3.0 mg/d will be terminated at week 20, and participants will have a final safety assessment at week 24.

The primary endpoint of the 12-week extension trial is change in body weight (i.e., % reduction in randomization weight), as measured from randomization (week 0) to week 12. Secondary endpoints include the proportion of subjects who lose > 5% or > 10% of initial weight from randomization to week 12, as well as changes from randomization to week 12 in cardiovascular disease (CVD) risk factors (i.e, blood pressure, triglycerides, LDL and HDL cholesterol, and waist circumference), glycemic control (i.e., fasting blood sugar), mood (PHQ-9), quality of life (i.e, SF-36 and IWQOL-Lite), eating behavior (i.e., Eating Inventory, Eating Disorder Examination-Questionnaire, and Yale Food Addiction Scale), appetite (i.e., visual analogue scales), sleep (i.e., Pittsburgh Sleep Quality Index), and weight loss satisfaction. (All of these measures were administered in the original 1-year trial.)

Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).

All data analyses will proceed using the same principles and methods used in the original protocol.

02

Conditions studied

  • Obesity
03

In context

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  1. Participants must have a BMI ≥ 30 and ≤ 55 kg/m²
  2. Age ≥ 21 years and ≤ 70 years

  3. Eligible female patients will be:

    • non-pregnant, evidenced by a negative urine dipstick pregnancy test
    • non-lactating
    • surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study
  4. Ability to provide informed consent before any trial-related activities

  5. Participants must:

    • have a primary care provider (PCP) who is responsible for providing routine care
    • have a reliable telephone service with which to communicate with study staff
    • understand and be willing to comply with all study-related procedures and agree to participate in the study by giving written informed consent
    • plan to remain in the Philadelphia area for the next 18 months

Exclusion Criteria:

  1. Pregnant or nursing, or plans to become pregnant in the next 18 months, or not using adequate contraceptive measures
  2. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
  3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
  4. Type 1 diabetes
  5. Type 2 diabetes
  6. A fasting glucose ≥ 126 mg/dl (on second assessment after first elevated value)
  7. Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the past 6 months), congestive heart failure, or heart block greater than first degree
  8. Clinically significant hepatic or renal disease
  9. Thyroid disease, not controlled
  10. History of malignancy (except for non-melanoma skin cancer) in past 5 years
  11. Current major depressive episode, active suicidal ideation, or history of suicide attempts
  12. Psychiatric hospitalization within the past 6 months
  13. Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
  14. Use in past 3 months of medications known to induce significant weight loss (i.e., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics)
  15. Loss of ≥ 10 lb of body weight within the past 3 months
  16. History of (or plans for) bariatric surgery
  17. Inability to walk 5 blocks comfortably or engage in some other form of aerobic activity (e.g., swimming)
  18. Known or suspected allergy to trial medication(s), excipients, or related products
  19. Hypersensitivity to liraglutide or any product components
  20. The receipt of any investigational drug within 6 months prior to this trial
  21. Previous participation in this trial (e.g., randomized and failed to participate)
  22. History of pancreatitis
  23. Subjects will be included/excluded according to the latest updated US PI.

12-Week Extension Trial:

Inclusion Criteria

Inclusion criteria are those described for the original 1-year trial (enumerated above). The principal exception from these criteria is that participants will only be required to have a BMI > 27 kg/m2, with or without co-morbidities, to be eligible to participate in the extension study. All participants will have met BMI inclusion criteria when they initiated the use of liraglutide and now will use it, potentially with phentermine 15 mg/d, to facilitate to the maintenance of lost weight. (Liraglutide is approved for chronic weight management, including following successful weight loss.) We do not wish to enroll participants with a BMI \< 27 kg/m2 because of the possibility that they could reduce substantially below a BMI of 24.9 kg/m2, the upper limit of "normal" weight.

Exclusion Criteria:

Exclusion criteria will include those listed in the original protocol, including those specific to the use of liraglutide 3.0 mg/d (e.g., family history of medullary thyroid cancer).

Additional exclusion criteria added to the 12-week extension study are specific to the use of phentermine 15 mg/d. They include:

  1. Use of monoamine oxidase inhibitors in the past 2 weeks
  2. Glaucoma
  3. Presence or history of marked agitation
  4. History of drug abuse
  5. Known hypersensitivity to sympathomimetic amines
  6. Current use of selective serotonin re-uptake inhibitors (e.g., fluoxetine, sertraline, etc)
  7. Current use of any other weight loss medications (besides liraglutide 3.0 mg/d)
  8. History of coronary artery disease
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
150 participants (actual)

Study arms

  • Active comparator
    CMS-Alone

    Lifestyle counseling, as currently recommended by the CMS.

    Behavioral: CMS-recommended lifestyle counseling

  • Active comparator
    CMS-Liraglutide

    CMS lifestyle counselling plus liraglutide.

    Behavioral: CMS-recommended lifestyle counseling · Drug: Liraglutide 3.0mg

  • Active comparator
    Multi-Component Intervention

    CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.

    Behavioral: CMS-recommended lifestyle counseling · Drug: Liraglutide 3.0mg · Other: Portion-Controlled Diet

  • Active comparator
    12-Week Extension Study: Phentermine Group

    After the 1-year trial, half the participants who join the extension study will be randomized to phentermine 15.0 mg/d in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study.

    Drug: Liraglutide 3.0mg · Drug: Phentermine 15 MG · Behavioral: Extension Study CMS-recommended lifestyle counseling

  • Active comparator
    12-Week Extension Study: Placebo Group

    After the 1-year trial, half the participants who join the extension study will be randomized to placebo in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study.

    Drug: Liraglutide 3.0mg · Drug: Placebo Oral Tablet · Behavioral: Extension Study CMS-recommended lifestyle counseling

Interventions

  • BehavioralCMS-recommended lifestyle counseling

    21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

  • DrugLiraglutide 3.0mg

    Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.

    Also known as: Saxenda

  • OtherPortion-Controlled Diet

    A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.

  • DrugPlacebo Oral Tablet
  • DrugPhentermine 15 MG
  • BehavioralExtension Study CMS-recommended lifestyle counseling

    4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

06

What researchers measure

Primary outcomes

  1. Percent Change in Baseline Weight

    Time frame: Randomization and 52 weeks

  2. Extension Study Primary Outcome: Percent Change in Re-randomization Weight

    Time frame: Re-randomization and 12 weeks

Secondary outcomes

  1. Change in Systolic Blood Pressure

    Time frame: Randomization and 52 weeks

  2. Change in Diastolic Blood Pressure

    Time frame: Randomization and 52 weeks

  3. Change in Heart Rate

    Time frame: Randomization and 52 weeks

  4. Change in Waist Circumference

    Time frame: Randomization and 52 weeks

  5. Change in Total Cholesterol

    Time frame: Randomization and 52 weeks

  6. Change in LDL Cholesterol

    Time frame: Randomization and 52 weeks

  7. Change in HDL Cholesterol

    Time frame: Randomization and 52 weeks

  8. Change in Triglycerides

    Time frame: Randomization and 52 weeks

  9. Change in C Reactive Protein

    Time frame: Randomization and 52 weeks

  10. Change in Fasting Glucose

    Time frame: Randomization and 52 weeks

  11. Change in HbA1c

    Time frame: Randomization and 52 weeks

  12. Change in Fasting Insulin

    Time frame: Randomization and 52 weeks

  13. Change in HOMA-IR

    HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement

    Time frame: Randomization and 52 weeks

  14. Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

    Time frame: Randomization and 52 weeks

  15. Change 36-Item Short Form Survey (SF-36) - Mental Component Summary

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

    Time frame: Randomization and 52 weeks

  16. Change in Patient Health Questionnaire (PHQ-9)

    PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.

    Time frame: Randomization and 52 weeks

  17. Extension Study Secondary Outcome: Change in Systolic Blood Pressure

    Time frame: Re-randomization and 12 weeks

  18. Extension Study Secondary Outcome: Change in Diastolic Blood Pressure

    Time frame: Re-randomization and 12 weeks

  19. Extension Study Secondary Outcome: Change in Heart Rate

    Time frame: Re-randomization and 12 weeks

  20. Extension Study Secondary Outcome: Change in Waist Circumference

    Time frame: Re-randomization and 12 weeks

  21. Extension Study Secondary Outcome: Change in Total Cholesterol

    Time frame: Re-randomization and 12 weeks

  22. Extension Study Secondary Outcome: Change in LDL Cholesterol

    Time frame: Re-randomization and 12 weeks

  23. Extension Study Secondary Outcome: Change in HDL Cholesterol

    Time frame: Re-randomization and 12 weeks

  24. Extension Study Secondary Outcome: Change in Triglycerides

    Time frame: Re-randomization and 12 weeks

  25. Extension Study Secondary Outcome: Change in c-Reactive Protein

    Time frame: Re-randomization and 12 weeks

  26. Extension Study Secondary Outcome: Change in Fasting Glucose

    Time frame: Re-randomization and 12 weeks

  27. Extension Study Secondary Outcome: Change in HbA1c

    Time frame: Re-randomization and 12 weeks

  28. Extension Study Secondary Outcome: Change in Fasting Insulin

    Time frame: Re-randomization and 12 weeks

  29. Extension Study Secondary Outcome: Change in HOMA-IR

    HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement

    Time frame: Re-randomization and 12 weeks

  30. Extension Study Secondary Outcome: SF-36 - Physical Health Component

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

    Time frame: Re-randomization and 12 weeks

  31. Extension Study Secondary Outcome: SF-36 - Mental Health Component

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

    Time frame: Re-randomization and 12 weeks

  32. Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9)

    PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.

    Time frame: Re-randomization and 12 weeks

07

Results

Posted May 7, 2019

Participant flow

This trial enrolled 150 participants for the original 52-week study. The 12-week extension study randomized 45 participants from the 100 eligible from the original 52-week trial who were originally in either the CMS-Liraglutide or Multi-Component groups. Eligible participants for the 12-week extension had to complete 1 year on liraglutide.

52 Week Study
Participant flow — 52 Week Study
MilestoneCMS-AloneCMS-LiraglutideMulti-Component Intervention12-Week Extension Study: Phentermine Group12-Week Extension Study: Placebo Group
Started50505000
Completed46454600
Not completed45400
12 Week Extension Study
Participant flow — 12 Week Extension Study
MilestoneCMS-AloneCMS-LiraglutideMulti-Component Intervention12-Week Extension Study: Phentermine Group12-Week Extension Study: Placebo Group
Started0002223
Completed0002222
Not completed00001

Outcome measures

PrimaryPercent Change in Baseline Weight
Time frame:
Randomization and 52 weeks
Reported as:
Mean · percent change
Percent Change in Baseline Weight
percent changeCMS-AloneCMS-LiraglutideMulti-Component Intervention
Percent Change in Baseline Weight-6.1 ± 1.3-11.5 ± 1.3-11.8 ± 1.3
PrimaryExtension Study Primary Outcome: Percent Change in Re-randomization Weight
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · percent change
Extension Study Primary Outcome: Percent Change in Re-randomization Weight
percent change12-Week Extension Study: Phentermine Group12-Week Extension Study: Placebo Group
Extension Study Primary Outcome: Percent Change in Re-randomization Weight-1.6 ± 0.6-0.1 ± 0.5
SecondaryChange in Systolic Blood Pressure
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mm Hg
Change in Systolic Blood Pressure
mm HgCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Systolic Blood Pressure-14.1 ± 2.1-13.3 ± 2.1-15.3 ± 2.1
SecondaryChange in Diastolic Blood Pressure
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mm Hg
Change in Diastolic Blood Pressure
mm HgCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Diastolic Blood Pressure-3.0 ± 1.2-2.9 ± 1.2-3.5 ± 1.2
SecondaryChange in Heart Rate
Time frame:
Randomization and 52 weeks
Reported as:
Mean · Beats per minute
Change in Heart Rate
Beats per minuteCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Heart Rate-7.4 ± 2.0-5.3 ± 2.09.7 ± 2.0
SecondaryChange in Waist Circumference
Time frame:
Randomization and 52 weeks
Reported as:
Mean · cm
Change in Waist Circumference
cmCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Waist Circumference-6.5 ± 1.3-11.1 ± 1.3-12.6 ± 1.3
SecondaryChange in Total Cholesterol
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/dL
Change in Total Cholesterol
mg/dLCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Total Cholesterol-7.0 ± 3.5-9.7 ± 3.6-10.0 ± 3.5
SecondaryChange in LDL Cholesterol
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/dL
Change in LDL Cholesterol
mg/dLCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in LDL Cholesterol-3.3 ± 3.1-9.6 ± 3.1-9.4 ± 3.1
SecondaryChange in HDL Cholesterol
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/dL
Change in HDL Cholesterol
mg/dLCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in HDL Cholesterol-1.3 ± 1.33.0 ± 1.32.0 ± 1.3
SecondaryChange in Triglycerides
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/dL
Change in Triglycerides
mg/dLCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Triglycerides-16.3 ± 5.7-21.3 ± 5.8-14.4 ± 5.7
SecondaryChange in C Reactive Protein
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/L
Change in C Reactive Protein
mg/LCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in C Reactive Protein-0.4 ± 0.7-2.0 ± 0.7-3.0 ± 0.7
SecondaryChange in Fasting Glucose
Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/dL
Change in Fasting Glucose
mg/dLCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Fasting Glucose0.01 ± 1.3-5.2 ± 1.3-5.7 ± 1.3
SecondaryChange in HbA1c
Time frame:
Randomization and 52 weeks
Reported as:
Mean · percentage
Change in HbA1c
percentageCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in HbA1c-0.3 ± 0.03-0.5 ± 0.03-0.6 ± 0.03
SecondaryChange in Fasting Insulin
Time frame:
Randomization and 52 weeks
Reported as:
Mean · uIU/mL
Change in Fasting Insulin
uIU/mLCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Fasting Insulin-1.5 ± 0.8-1.1 ± 0.8-1.5 ± 0.8
SecondaryChange in HOMA-IR

HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement

Time frame:
Randomization and 52 weeks
Reported as:
Mean · mg/dL*µIU/mL/405
Change in HOMA-IR
mg/dL*µIU/mL/405CMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in HOMA-IR-0.4 ± 0.2-0.3 ± 0.2-0.4 ± 0.2
SecondaryChange in 36-Item Short Form Survey (SF-36) - Physical Component Summary

All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

Time frame:
Randomization and 52 weeks
Reported as:
Mean · T scores
Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary
T scoresCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary4.4 ± 1.02.1 ± 1.03.4 ± 1.0
SecondaryChange 36-Item Short Form Survey (SF-36) - Mental Component Summary

All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

Time frame:
Randomization and 52 weeks
Reported as:
Mean · T scores
Change 36-Item Short Form Survey (SF-36) - Mental Component Summary
T scoresCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change 36-Item Short Form Survey (SF-36) - Mental Component Summary0.8 ± 1.34.5 ± 1.36.4 ± 1.3
SecondaryChange in Patient Health Questionnaire (PHQ-9)

PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.

Time frame:
Randomization and 52 weeks
Reported as:
Mean · score on a scale
Change in Patient Health Questionnaire (PHQ-9)
score on a scaleCMS-AloneCMS-LiraglutideMulti-Component Intervention
Change in Patient Health Questionnaire (PHQ-9)-1.8 ± 0.6-1.9 ± 0.6-1.5 ± 0.6
SecondaryExtension Study Secondary Outcome: Change in Systolic Blood Pressure
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mm Hg
Extension Study Secondary Outcome: Change in Systolic Blood Pressure
mm Hg12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Systolic Blood Pressure1.2 ± 2.12.0 ± 2.1
SecondaryExtension Study Secondary Outcome: Change in Diastolic Blood Pressure
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mm Hg
Extension Study Secondary Outcome: Change in Diastolic Blood Pressure
mm Hg12-Week Extension Study: Phentermine Group12-Week Extension Study: Placebo Group
Extension Study Secondary Outcome: Change in Diastolic Blood Pressure1.3 ± 1.60.2 ± 1.6
SecondaryExtension Study Secondary Outcome: Change in Heart Rate
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · Beats per minute
Extension Study Secondary Outcome: Change in Heart Rate
Beats per minute12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Heart Rate0 ± 1.42.1 ± 1.4
SecondaryExtension Study Secondary Outcome: Change in Waist Circumference
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · cm
Extension Study Secondary Outcome: Change in Waist Circumference
cm12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Waist Circumference-0.6 ± 0.8-0.4 ± 0.8
SecondaryExtension Study Secondary Outcome: Change in Total Cholesterol
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/dL
Extension Study Secondary Outcome: Change in Total Cholesterol
mg/dL12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Total Cholesterol3.4 ± 3.30.4 ± 3.3
SecondaryExtension Study Secondary Outcome: Change in LDL Cholesterol
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/dL
Extension Study Secondary Outcome: Change in LDL Cholesterol
mg/dL12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in LDL Cholesterol2.3 ± 2.8-2.4 ± 2.8
SecondaryExtension Study Secondary Outcome: Change in HDL Cholesterol
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/dL
Extension Study Secondary Outcome: Change in HDL Cholesterol
mg/dL12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in HDL Cholesterol0.6 ± 1.42.0 ± 1.4
SecondaryExtension Study Secondary Outcome: Change in Triglycerides
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/dL
Extension Study Secondary Outcome: Change in Triglycerides
mg/dL12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Triglycerides4.1 ± 4.76.6 ± 4.7
SecondaryExtension Study Secondary Outcome: Change in c-Reactive Protein
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/L
Extension Study Secondary Outcome: Change in c-Reactive Protein
mg/L12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in c-Reactive Protein-0.8 ± 0.6-0.6 ± 0.6
SecondaryExtension Study Secondary Outcome: Change in Fasting Glucose
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/dL
Extension Study Secondary Outcome: Change in Fasting Glucose
mg/dL12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Fasting Glucose1.4 ± 1.66.3 ± 1.6
SecondaryExtension Study Secondary Outcome: Change in HbA1c
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · percentage
Extension Study Secondary Outcome: Change in HbA1c
percentage12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in HbA1c0.0 ± 0.10.0 ± 0.0
SecondaryExtension Study Secondary Outcome: Change in Fasting Insulin
Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · uIU/mL
Extension Study Secondary Outcome: Change in Fasting Insulin
uIU/mL12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in Fasting Insulin0.2 ± 1.00.5 ± 1.0
SecondaryExtension Study Secondary Outcome: Change in HOMA-IR

HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement

Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · mg/dL*µIU/mL/405
Extension Study Secondary Outcome: Change in HOMA-IR
mg/dL*µIU/mL/40512-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Change in HOMA-IR0.1 ± 0.20.3 ± 0.2
SecondaryExtension Study Secondary Outcome: SF-36 - Physical Health Component

All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · T scores
Extension Study Secondary Outcome: SF-36 - Physical Health Component
T scores12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: SF-36 - Physical Health Component0.3 ± 1.0-1.2 ± 1.0
SecondaryExtension Study Secondary Outcome: SF-36 - Mental Health Component

All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health. Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10. Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.

Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · T scores
Extension Study Secondary Outcome: SF-36 - Mental Health Component
T scores12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: SF-36 - Mental Health Component-0.1 ± 1.10.2 ± 1.1
SecondaryExtension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9)

PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.

Time frame:
Re-randomization and 12 weeks
Reported as:
Mean · score on a scale
Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9)
score on a scale12-Week Extension Study: Placebo Group12-Week Extension Study: Phentermine Group
Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9)0.2 ± 0.40.0 ± 0.4

Adverse events

Collected over 52-weeks post randomization for the original trial; 12-weeks for the extension trial post extension randomization. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CMS-Alone0/50 (0%)2/50 (4%)21/50 (42%)
CMS-Liraglutide0/50 (0%)0/50 (0%)42/50 (84%)
Multi-Component Intervention0/50 (0%)3/50 (6%)44/50 (88%)
12-Week Extension Study: Phentermine Group1/22 (4.5%)1/22 (4.5%)12/22 (54.5%)
12-Week Extension Study: Placebo Group0/23 (0%)0/23 (0%)11/23 (47.8%)
Most frequent serious events
Most frequent serious events
EventCMS-AloneCMS-LiraglutideMulti-Component Intervention12-Week Extension Study: Phentermine Group12-Week Extension Study: Placebo Group
Quadriplegic eventNervous system disorders0/500/500/501/220/23
Asthma ExacerbationRespiratory, thoracic and mediastinal disorders1/500/500/500/220/23
Bile duct stoneHepatobiliary disorders0/500/501/500/220/23
GastroenteritisGastrointestinal disorders0/500/501/500/220/23
PneumoniaRespiratory, thoracic and mediastinal disorders0/500/501/500/220/23
Wound infectionInfections and infestations1/500/500/500/220/23
Most frequent other events
Showing 10 of 21
Most frequent other events
EventCMS-AloneCMS-LiraglutideMulti-Component Intervention12-Week Extension Study: Phentermine Group12-Week Extension Study: Placebo Group
NauseaGastrointestinal disorders4/5018/5013/502/221/23
ConstipationGastrointestinal disorders1/5015/5017/500/220/23
Upper respiratory infectionRespiratory, thoracic and mediastinal disorders8/5016/5014/501/222/23
Musculoskeletal injuryMusculoskeletal and connective tissue disorders6/506/5012/501/225/23
GastroenteritisGastrointestinal disorders2/5010/508/502/221/23
DiarrheaGastrointestinal disorders2/506/507/502/221/23
Gastroesophageal reflux disorderGastrointestinal disorders2/502/506/503/221/23
Injection site irritationSkin and subcutaneous tissue disorders0/505/506/500/220/23
VomittingGastrointestinal disorders3/506/505/500/220/23
SinusitisRespiratory, thoracic and mediastinal disorders3/502/505/500/220/23

Baseline characteristics

Age, Continuous
Age, Continuous(years)CMS-AloneCMS-LiraglutideMulti-Component InterventionTotal
Mean49.5 ± 11.045.2 ± 12.348.0 ± 11.947.6 ± 11.8
Sex: Female, Male
Sex: Female, Male(Participants)CMS-AloneCMS-LiraglutideMulti-Component InterventionTotal
Female394238119
Male1181231
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CMS-AloneCMS-LiraglutideMulti-Component InterventionTotal
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0011
Black or African American22232267
White27272781
More than one race1001
Unknown or Not Reported0000
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Study locations

1 site
  • University of Pennsylvania Center for Weight and Eating Disorders
    Philadelphia, Pennsylvania 19104, United States
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References and documents

Publications

  • Tronieri JS, Wadden TA, Walsh O, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Bakizada ZM, Chao AM. Effects of liraglutide on appetite, food preoccupation, and food liking: results of a randomized controlled trial. Int J Obes (Lond). 2020 Feb;44(2):353-361. doi: 10.1038/s41366-019-0348-6. Epub 2019 Mar 29. PubMed 30926955 ↗
  • Tronieri JS, Wadden TA, Walsh OA, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Chao AM. Effects of liraglutide plus phentermine in adults with obesity following 1 year of treatment by liraglutide alone: A randomized placebo-controlled pilot trial. Metabolism. 2019 Jul;96:83-91. doi: 10.1016/j.metabol.2019.03.005. Epub 2019 Mar 20. PubMed 30902750 ↗
  • Wadden TA, Walsh OA, Berkowitz RI, Chao AM, Alamuddin N, Gruber K, Leonard S, Mugler K, Bakizada Z, Tronieri JS. Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3.0 mg: A Randomized Controlled Trial. Obesity (Silver Spring). 2019 Jan;27(1):75-86. doi: 10.1002/oby.22359. Epub 2018 Nov 13. PubMed 30421856 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 25, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 7, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02911818
Lead sponsor
University of Pennsylvania
Collaborators
Novo Nordisk A/S
Responsible party
Sponsor
First posted
Sep 22, 2016
Start date
Sep 2016
Primary completion
Nov 2018
Completion
Dec 2018
Results posted
May 7, 2019
Last update
May 7, 2019

Study contacts

Thomas A Wadden, Ph.D.
principal investigator · University of Pennsylvania, Center for Weight and Eating Disorders
View the source record on ClinicalTrials.gov ↗

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