EMI-EHP Weight Management and Type 2 Diabetes Pragmatic Trial

Study Overview
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Brief Summary
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This is a pragmatic, 24 month, single-center, randomized, open-label, parallel-group trial comparing an obesity-centric approach with a medically-supervised and comprehensive weight loss program (Cleveland Clinic's Endocrinology and Metabolism Institute's Integrated Weight Management Program) augmented by AOMs, vs. an obesity-centric approach with a medically-supervised and comprehensive weight loss program without AOMs, vs. the current usual care approach to general health management. Informed consent will be obtained. IRB approval of the study will be obtained. 300 subjects (employees or spouses covered by our EHP) will be randomized 1:1:1 to receive either an obesity-centric approach with AOM therapy (N=100), an obesity-centric approach without AOM therapy (N=100), or the current usual care approach to general health management (N=100).

Detailed Description
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Obesity affects nearly 40% of adults in the US and it is responsible for important medical problems including hypertension, dyslipidemia, T2D, depression, coronary heart disease, stroke, osteoarthritis, obstructive sleep apnea (OSA), fatty liver disease, and some cancers, to name a few4,5. Obesity is responsible for the development of T2D and hypertension in more than 90% and 50% of cases, respectively6-7. Also more than 70% of patients with obesity have dyslipidemia. The prevalence of depression in patients with obesity is more than 50% and obesity is responsible for causing osteoarthritis in more than 25% of the patients8. Also, in the adult population, the prevalence of OSA is estimated to be  25%, and as high as 45% in subjects with obesity9. Patients with obesity have an increased risk of all-cause and cardiovascular death. In recognition of the biologic basis and seriousness of obesity, several professional health associations and organizations worldwide recognize obesity as a disease10. Even though there is clear evidence in the literature that weight loss is associated with a dramatic improvement of obesity-related comorbidities and the patient's quality of life, in general, clinicians all over the world focus their attention on treating the diabetes, hypertension, hyperlipidemia and other comorbidities rather than the obesity itself, concentrating their efforts on improving blood glucose indices, blood pressure and LDL as well as triglycerides, and in many instances, prescribing anti-diabetes and antihypertensive medications that potentiate further weight gain11,12. As a result, clinicians are faced with a rising epidemic of obesity, perpetuating a preexisting epidemic of diabetes, hypertension, dyslipidemia, and metabolic syndrome. Obesity is one of the biggest drivers of preventable chronic diseases and healthcare costs in the United States. Currently, estimates for these costs are $210 billion per year. In addition, obesity is associated with job absenteeism and with lower productivity while at work costing approximately $4.3 billion annually12,13. As a person's BMI increases, so do the number of sick days, medical claims and healthcare costs. Individuals who suffer obesity spend 42% more on direct healthcare costs than adults who have a healthy weight. Individuals with grade 1 obesity (BMI between 30 and 35) are more than twice as likely as individuals with BMI < 30 to be prescribed prescription pharmaceuticals to manage medical conditions14. Reducing obesity, improving nutrition, increasing physical activity, and making lifelong meaningful lifestyle changes can help lower costs through fewer doctor's office visits, tests, prescription drugs, sick days, emergency room visits and admissions to the hospital and lower the risk for a wide range of diseases. A 2008 study by the Urban Institute, The New York Academy of Medicine and Trust for America's Health found that an investment of $10 per person in proven community-based programs to increase physical activity, improve nutrition, and prevent smoking and other tobacco use could save the country more than $16 billion annually within five years. That's a return of $5.60 for every $1 invested15. In spite of these important facts there is a significant, yet much-underutilized role, for structured weight management programs, both with and without use of anti-obesity medications, to improve metabolic control for patients with obesity who have developed comorbidities such as hypertension hyperlipidemia and T2D. Unfortunately, these patients have a much higher risk of developing coronary artery disease and cancer. The medical literature contains ample evidence which demonstrates the positive impact that a lifestyle intervention program augmented by FDA approved AOMs can have on anthropometric and metabolic parameters in patients with obesity who have developed significant comorbidities16-17. Lifestyle intervention, in the form of improving diet, eating behaviors and increasing physical activity, is first-line treatment for obesity and overweight, but the majority of people with obesity and overweight struggle to achieve and maintain their weight loss long-term. We hypothesize that an obesity-centric approach delivered through a medically-supervised and comprehensive weight loss program18, augmented by AOM, as the primary treatment of patients with obesity and T2D, will result in greater and sustainable weight loss, a better metabolic profile, (including glycemic blood pressure and cholesterol control) and improved quality of life (QOL) and treatment satisfaction when compared to an obesity-centric approach without AOM therapy or the current usual care/standard of care comorbidity-centric approach to general health management in patients with obesity and T2D. If confirmed, these findings would be expected to change our future approach to chronic diseases management, and reduce the rates of T2D, hypertension, and hyperlipidemia related complications (including heart disease and cancer) as well as the development of other obesity-related comorbidities, potentially reducing the long-term cost of care

Official Title
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An ObEsity-centric Approach With and Without Anti-obesity Medications ComPared to the Usual-care ApprOach to Management of Patients With Obesity and Type 2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled Trial

Conditions
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Type 2 Diabetes, Obesity

Intervention / Treatment
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* Other: Weight Management Program (WMP)
* Other: Traditional care
* Drug: Phentermine / Topiramate Extended Release Oral Capsule
* Drug: naltrexone/bupropion extended-release
* Drug: liraglutide 3.0 mg
* Drug: Orlistat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gender: men and women Ethnicity: all ethnic groups Age: ≥18, < 75 years Diagnosis of T2D -A1C within the last 90 days must be >7.5% Obesity, BMI ≥30 An Employee, or the significant other of an employee, that is covered by the Cleveland Clinic Employee Health Plan Exclusion Criteria: Type 1 diabetes or known latent autoimmune diabetes of adulthood (LADA) Glomerular Filtration Rate <30 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration Equation, CKD-EPI) Current glucocorticoid therapy Currently or within the past 3 months receiving an anti-obesity medication, or any other medication used for the primary intent of weight loss Any condition, unwillingness or inability, not covered by any of the other exclusion criteria, which, in the study clinician's opinion, might jeopardize the subject's safety or compliance with the protocol Mental incapacity or language barrier Pregnancy or plans to become pregnant within the next 2 years Personal or family history of medullary thyroid carcinoma Personal or family history of Multiple Endocrine Neoplasia syndrome type 2 History of acute pancreatitis, severe liver disease (Cirrhosis), or severe disease of digestive tract History of congestive heart failure History of bariatric or metabolic surgery/procedure Visit with an endocrinologist within the past 1 year Prior participation in the Endocrinology and Metabolism Institutes Integrated Weight Management Program

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obesity-centric approach + AOM<br>Participants will receive Cleveland Clinic's Integrated Medical WMP with medication for chronic weight management (Rx) for approximately two years. After discussing with the study doctor, participants will receive one of the following listed 4 drugs approved by the Food and Drug Administration (FDA) for long-term weight loss: 1) orlistat, 2) phentermine/topiramate extended-release, 3) naltrexone/bupropion extended-release and 4) liraglutide 3.0 mg | Other: Weight Management Program (WMP)<br>* Weight Management Program (WMP)<br>Drug: Phentermine / Topiramate Extended Release Oral Capsule<br>* Medication for chronic weight management (Rx)<br>Drug: naltrexone/bupropion extended-release<br>* Medication for chronic weight management (Rx)<br>Drug: liraglutide 3.0 mg<br>* Medication for chronic weight management (Rx)<br>Drug: Orlistat<br>* Medication for chronic weight management (Rx)<br>|
| Experimental: Obesity-centric approach without AOM<br>Participants will receive Cleveland Clinic's Integrated Medical WMP alone for approximately two years. | Other: Weight Management Program (WMP)<br>* Weight Management Program (WMP)<br>|
| Active Comparator: Usual care approach (Comorbidity-centric approach)<br>Participants will receive the traditional usual care/standard of care approach to T2D, hypertension, hypercholesterolemia management for approximately two years. | Other: Traditional care<br>* Traditional care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Measured in percentage | 12 Months | 
| Change in A1C | Measured in percentage | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Measured in percentage | 24 Months | 
| Change in A1C | Measured in percentage | 24 Months | 
| Efficacy of medication | Measured in percentage of weight loss | 24 Months | 
| Participants achieving 5% ore more reduction in body weight | Percentage of participants achieving weight loss at 6, 12 and 24 months | 24 Months | 
| Mean weight loss at 6 months | Change from baseline in body weight at 6 months | 24 Months | 
| Participants achieving A1c less than 7.0% | Percentage of participants achieving target of A1C less than 7.0% at 6, 12 and 24 months | 24 Months | 
| Mean A1C at 6 months | Change from baseline in A1C at 6 months | 24 Months | 
| Mean Serum LDL, HDL | Change from baseline in serum LDL, HDL at 6, 12 and 24 months | 24 Months | 
| Mean Serum triglycerides | Change from baseline in serum triglycerides at 6, 12 and 24 months | 24 Months | 
| Participants achieving blood pressure less than 140/90 mmHg | Percentage of participants achieving target less than 140/90 mmHg at 6, 12 and 24 months | 24 Months | 
| Mean Quality of Life (QOL) questionnaire | Mean change from baseline in survey scores at 6, 12, 24 months | 24 Months | 
| Mean total cost of care | Determined per claims data from our EHP at 12 and 24 months | 24 Months |