Insulin for Obesity

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must not be taking: Niacin, Thiazolidinediones, Beta-blockers, others

Disqualifiers: Ischemic heart disease, Diabetes, Smokers, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why individuals with excess abdominal weight respond differently to insulin compared to lean individuals. Researchers administer insulin to observe how various types of body fat react. The trial includes two groups: individuals with obesity and those who are lean. It suits adults who are overweight, particularly those with excess abdominal weight. As an Early Phase 1 trial, this research focuses on understanding insulin treatment in people, offering participants the chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that can affect fat metabolism, like niacin, thiazolidinediones, beta-blockers, and steroids. If you're on these, you may need to stop them to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that insulin is generally safe for various uses. Studies have found that different types of insulin, such as insulin detemir and glargine, are usually well-tolerated. Specifically, insulin detemir is linked to less weight gain compared to other types. Insulin glargine has been studied for over six years and has not shown any major effects on heart health or cancer risk.

However, side effects can occur. Some people may experience low blood sugar (hypoglycemia), especially with certain types of insulin. Proper monitoring can usually manage this. Overall, insulin is a well-established treatment, and its safety is well-documented. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for obesity, such as lifestyle changes, medications, and surgical options, the use of insulin in this context is unique because it explores a potential new role for a hormone traditionally associated with diabetes management. Researchers are excited about insulin's potential to influence metabolism in a way that could help manage or reduce obesity. This approach is particularly intriguing because it could offer a novel mechanism for weight control, differing from typical methods that primarily focus on appetite suppression or calorie absorption. By investigating insulin's effects on obesity, there’s hope for a new pathway to tackle weight issues, possibly providing an alternative for those who haven't found success with existing treatments.

What evidence suggests that insulin might be an effective treatment for obesity?

Research shows that insulin typically controls blood sugar levels, especially in people with diabetes. Some studies have demonstrated its effectiveness in maintaining stable blood sugar. However, its role in treating obesity, particularly for those with belly fat, remains unclear. This trial will explore insulin's effects on different body types, categorizing participants into separate arms based on obesity status. The aim is to understand why insulin might work differently in people with various body types. Early findings suggest insulin may affect fat tissue differently depending on body type, but more research is needed to confirm its effectiveness for obesity. ^{3 6 7 8 9}

Who Is on the Research Team?

Michael D Jensen, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for overweight or obese adults aged 18-65 with a BMI of 29.0 - 37.0, who carry extra weight mainly in the abdominal area. Participants must follow a specific diet for three days before the study and be able to understand and follow instructions. Pregnant or nursing women, smokers, those with certain allergies, high blood pressure not controlled by medication, heart disease history, diabetes diagnosis, or on drugs affecting fat metabolism cannot join.

Inclusion Criteria

I will eat only provided meals from Mayo CRTU for 3 days before the study.

Lower body obesity (LBO) criteria for women and men

My BMI is between 29.0 and 37.0.

Exclusion Criteria

Smokers

Allergy to indocyanine green

Allergy to lidocaine

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Measure regional free fatty acid (FFA) release in volunteers under different conditions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Insulin

Trial Overview Researchers are studying how insulin affects fat tissue in people with different body types—specifically comparing responses between those who gain weight primarily in their abdomen versus other areas.

How Is the Trial Designed?

Group I: obesity status Experimental Treatment 1 Intervention

obesity

Group II: lean Experimental Treatment 1 Intervention

non-obese

Insulin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Insulin for:

• Diabetes mellitus

Approved in United States as Insulin for:

• Diabetes mellitus

Approved in Canada as Insulin for:

• Diabetes mellitus

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A comprehensive review of 50 studies over the past 20 years revealed significant differences in bioactivity between human insulin and various insulin analogues, affecting metabolism, cell growth, and other cellular functions.

The clinical implications of these differences in bioactivity are still unclear and require further investigation to understand their impact on different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years. Werner, H., Chantelau, EA.[2021]

In a study involving 1008 patients, short-acting insulin lispro and regular insulin Humulin R showed similar effectiveness in controlling blood sugar levels and had comparable safety profiles, with no significant differences in hypoglycemia incidents.

After a year of continued lispro therapy, glycosylated hemoglobin (HbA1C) levels returned to baseline, indicating that while lispro was well tolerated in the short term, long-term efficacy may need further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lispro insulin as premeal therapy in type 1 diabetes: comparison with Humulin R. Daniels, AR., Bruce, R., McGregor, L.[2022]

In a study of 460 adults with type 2 diabetes who were previously inadequately controlled on other insulin types, initiating basal insulin analogues led to a significant reduction in glycated hemoglobin (HbA1c) by 1.8% over 6 months, indicating improved glycemic control.

The use of basal insulin analogues also significantly decreased the incidence of symptomatic hypoglycemia from 96.3% to 15.4%, while not adversely affecting body weight, waist circumference, or BMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Basal Insulin Analogue Treatment in Persons with Type 2 Diabetes Inadequately Controlled on Prior Insulin Therapy: A Prospective, Noninterventional, Multicenter Study. Bjekić-Macut, J., Živković, TB., Kocić, R.[2020]

Insulin detemir is an effective long-acting insulin for managing type 2 diabetes, providing consistent blood glucose control for up to 24 hours while reducing the risk of nocturnal hypoglycemia and weight gain compared to other basal insulins.

Properly titrated insulin therapy, including insulin detemir, is the most physiological approach to lowering blood glucose and may help preserve beta-cell function, addressing common concerns about insulin use in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin detemir: a new option for the treatment of diabetes. Funnell, MM.[2022]

In a 32-week study involving 686 patients with Type 2 diabetes, insulin detemir (IDet) therapy was found to be safe, with no serious adverse drug reactions reported and a significant reduction in total hypoglycemic events from 435 to 204.

Patients experienced improved glycemic control, as indicated by a decrease in glycated hemoglobin A1c from 9.9% to 7.7% and fasting plasma glucose from 11.9 mmol/L to 7.4 mmol/L, alongside a slight reduction in body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study. El Shiekh, AR., Farrag, HA., Ashour, T., et al.[2020]

Insulin analogues like insulin lispro and insulin aspart have a more rapid onset and shorter duration of action compared to conventional human insulin, which may improve flexibility in managing blood sugar levels.

However, these analogues do not significantly change overall blood sugar control (measured by hemoglobin A1c levels) or reduce the risk of hypoglycemia compared to standard human insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on insulin analogues. [2019]

Treatment with humulin insulins showed high clinical effectiveness in managing diabetes, as evidenced by decreased insulin doses, stable diabetes compensation, and a reduction in insulin antibodies.

Humulin insulins are preferred over iletin-II due to their low immunogenicity, which means they are less likely to provoke an immune response and complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of highly purified Iletin-II-type porcine insulins and human insulin preparations in clinical practice]. Petunina, NA., Balabolkin, MI., Mkrtumian, AM., et al.[2011]

Insulin detemir is a long-acting insulin analog developed by Novo Nordisk for treating type 1 and type 2 diabetes, showing promise for effective blood sugar management.

As of early 2003, regulatory submissions for approval were made to both the FDA and Canadian authorities, indicating a strong push towards making this treatment available to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin detemir. Novo Nordisk. Barlocco, D.[2015]

A comparison of insulin lispro and regular human insulin (Humulin R) in 3634 patients with type 1 and type 2 diabetes showed no significant differences in treatment-emergent adverse events, indicating similar safety profiles for both insulins.

Both insulin therapies did not differ in their effects on the progression of chronic diabetes complications, such as retinopathy, neuropathy, cardiovascular disease, or kidney disease, suggesting that insulin lispro is as safe as Humulin R.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of insulin lispro: pooled data from clinical trials. Glazer, NB., Zalani, S., Anderson, JH., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6099315/

Clinical effectiveness of liraglutide vs basal insulin in a real ... The results of this real‐world study in matched obese patients with T2DM showed that liraglutide was more effective than BOT for HbA1c control and weight/BMI ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2572551/

Insulin Analogs: Impact on Treatment Success, Satisfaction ... The Cochrane review of study data with rapid-acting insulin analogs also found a lower median incidence of severe hypoglycemic episodes per 100 person-years ( ...

3. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.16386

Real world evidence of insulin and biosimilar insulin therapy ... Real-world evidence from real-world data plays a crucial role in assessing the safety, efficacy, cost-effectiveness, adherence to, and impacts ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1530891X21010661

Treatment Patterns and Outcomes, Before and After ... U-500R initiation was associated with significantly improved treatment compliance patterns and glycemic control, with modest increase in hypoglycemia events.

5. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1286827/full

Efficacy and safety of basal insulins in people with type 2 ... The present study's findings indicate that newer-generation basal insulins do not seem to improve glycemic control compared to first-generation ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10397971/

and Intermediate-Acting Insulin and Key Safety Outcomes ... We also reported patient outcomes by (a) use of oral second-generation sulfonylureas (SU) and rapid-acting insulin (R) in conjunction with LAI or NPH insulin; ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3267521/

Insulin detemir for the treatment of obese patients with type 2 ... Results from clinical trials have demonstrated that treatment with insulin detemir is associated with less weight gain than either insulin glargine or neutral ...

8. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.16295

Insulin glargine 300 U/mL safety data in pregnancy HIP is a risk factor for adverse maternal, foetal and neonatal outcomes such as spontaneous abortion, foetal anomalies, pre-eclampsia, preterm ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1203858

Basal Insulin and Cardiovascular and Other Outcomes in ... When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers.