Detemir for Obesity

(IDIOM Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University

Must be taking: Metformin, Sitagliptin, Thiazolidinediones

Must not be taking: Steroids, Appetite suppressants

Disqualifiers: Cardiovascular disease, Substance abuse, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 24 weeks

240 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants can be on certain diabetes medications like metformin, sitagliptin, or thiazolidines. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Detemir for obesity?

Research shows that insulin detemir, when used for type 2 diabetes, is associated with less weight gain compared to other insulins, which might be beneficial for managing weight in obese patients. ^{1 2 3 4 5}

How does the drug Detemir differ from other obesity treatments?

Detemir is unique in the context of obesity treatment as it is primarily known as an insulin analog used for diabetes management, which suggests a novel approach compared to traditional obesity drugs that focus on appetite suppression or fat absorption. This trial may explore its potential effects on metabolism and weight regulation, differing from existing options like orlistat or phentermine that target fat absorption and appetite, respectively. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to evaluate the effects of the medication insulin detemir on weight, brain function and mood, and on blood vessel and other risk factors for heart disease. The study will compare how diet and insulin detemir affect areas of the brain that are involved in food intake and the sense of pleasure people get from eating. Participants will be randomized into one of 2 groups. Group 1 will follow a low calorie diet only. Group 2 will follow a low calorie diet and take insulin detemir. The study is 26 weeks in length and include outpatient visits, inpatient visits, phone and email contact, questionnaires, diary collection, blood draw and procedures involving MRI and PET scans. There are 4 inpatient visits at the Vanderbilt Clinical Research Center (CRC). The inpatient visits require a one night 2 day stay on the CRC at Weeks 2, 6, 16, 26. During the weekly and bi-weekly outpatient visits participants will meet with the study nurse and dietitian.

Research Team

Kevin D Niswender, MD/PhD

Principal Investigator

Vanderbilt University

Eligibility Criteria

Adults aged 31-60 with stable obesity (BMI of 30-49), type 2 diabetes not on insulin, and a weight under 350lbs can join. They must have maintained their weight recently, be willing to follow diet plans, and avoid certain substances before visits. Those with significant health issues or conditions that affect study participation are excluded.

Inclusion Criteria

Stable body weight during the previous 3 months with a less than 5 pounds self -reported weight change

Informed consent obtained before any trial-related activities

Age at study entry is between 31-60 years of age

Exclusion Criteria

Dietary supplements of such as EPA, DHA or omega-3 fatty acids.

Previous surgery for weight loss

Any tobacco use in last 3 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomized into two groups: one receiving a low-calorie diet and insulin detemir, and the other receiving only a low-calorie diet. The treatment involves insulin detemir administration and dietary management.

24 weeks

Weekly visits (in-person and virtual)

Inpatient Monitoring

Participants undergo inpatient visits for detailed monitoring and procedures including MRI and PET scans.

26 weeks

4 inpatient visits (2 days each at Weeks 2, 6, 16, 26)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on weight loss and dopamine signaling.

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Detemir

Trial Overview The trial is testing if insulin detemir helps manage obesity when combined with a low-calorie diet compared to the diet alone. It will also look at effects on brain function, mood, heart disease risk factors through outpatient/inpatient visits involving questionnaires and scans over a period of 26 weeks.

Participant Groups

Group I: Insulin Detemir Treatment Experimental Treatment 1 Intervention

Insulin detemir treatment: Insulin detemir will be administered subcutaneously, once daily. Dose ranges from approximately 0.1 U/kg up to 0.6 u/kg or higher. The dosing regimen will employ a strategy similar to the "303"algorithm, where, with close interaction with study personnel (rather than self-titration), bedtime insulin dosing will be titrated up by 3 units until AM fasting sugars within the prescribed protocol range are achieved (90-110 mg/dl). Subjects will have contact with study personnel on weekly basis for glycemia monitoring and adjustments. Similarly, documented hypoglycemia (blood sugars less than 70) will trigger a dose reduction, and it is expected that with weight loss, tolerable insulin dosages will drift downward. The treatment period is 24 weeks.

Group II: Comparator: No insulin Active Control 1 Intervention

The main hypothesis is that "diabetes can be changed " with early and careful insulinization capturing effects on brain function ultimately leading to weight loss. . Seek to determine in a quantitative manner whether insulin detemir restores brain dopamine neurotransmission, a control group not treated with insulin is required. The strength of this study is our ability to test the specific molecular (D2R, DAT, functional MRI responses) and integrated output (functional brain responses, mood, cognitive function, reward responses etc.) of CNS dopaminergic pathways in order to shed unprecedented light upon mechanisms of detemir action in obesity and diabetes.

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

Two new medications, phentermine/topiramate ER (Qsymia™) and lorcaserin (Belviq®), have been approved by the FDA for long-term weight management in individuals with obesity or overweight with related health issues, marking a significant advancement in obesity treatment.

The review highlights that these new drugs are either reformulations of existing medications or new approaches targeting previously established mechanisms, indicating a trend of revisiting and optimizing older treatments for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic treatment options for obesity: what is old is new again. Ryan, DH., Bray, GA.[2021]

The FDA has approved lorcaserin and the combination of phentermine and extended-release topiramate (phentermine/topiramate ER) for obesity treatment, expanding options beyond orlistat and supporting long-term weight management alongside lifestyle changes.

Phentermine/topiramate ER has been shown to result in greater weight loss compared to using phentermine or topiramate alone, and it may also improve cardiometabolic risk factors, although more long-term safety data is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. Sweeting, AN., Tabet, E., Caterson, ID., et al.[2021]

Sibutramine, a serotonin/noradrenaline reuptake inhibitor, has been shown to reduce body weight by an average of 4.45 kg compared to placebo, while also improving triglycerides and HDL cholesterol, but it may cause increased heart rate and has contraindications for patients with uncontrolled hypertension or cardiovascular issues.

Orlistat, a pancreatic lipase inhibitor, results in an average weight loss of 2.89 kg and significantly decreases waist circumference and blood pressure, but primarily causes gastrointestinal side effects and should be avoided in patients with chronic malabsorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological therapy of obesity]. Pagotto, U., Vanuzzo, D., Vicennati, V., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Initiation of once daily insulin detemir is not associated with weight gain in patients with type 2 diabetes mellitus: results from an observational study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Weight change upon once-daily initiation of insulin detemir with or without dietary intervention in overweight or obese insulin-naïve individuals with type 2 diabetes: results from the DIET trial. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Are insulin analogues detemir or glulisine used preferentially in overweight/obese subjects? A German multicentre analysis of 38560 type 2 diabetic patients from the DPV registry. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Diabetes and weight management. [2012]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Insulin detemir results in less weight gain than NPH insulin when used in basal-bolus therapy for type 2 diabetes mellitus, and this advantage increases with baseline body mass index. [2018]

6. Chile pubmed.ncbi.nlm.nih.gov

[Anorexigenic drugs in the treatment of obesity]. [2006]

7. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic treatment options for obesity: what is old is new again. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. [2021]

9. Italy pubmed.ncbi.nlm.nih.gov

[Pharmacological therapy of obesity]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Orlistat in the treatment of obesity. [2022]