Insulin Pulses for Prediabetes

Overseen By Jeanette Laugen

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Glucose-lowering agents

Disqualifiers: High HbA1c, High BMI, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how insulin and glucagon, hormones that regulate blood sugar, affect fasting glucose levels in people with prediabetes. Researchers will test insulin's impact by using treatments like Intralipid and heparin to study insulin resistance, comparing these to a saline solution as a placebo. The goal is to learn how to better manage fasting blood sugar levels and prevent complications related to type 2 diabetes. This trial may suit individuals diagnosed with either normal or impaired fasting glucose levels who do not use glucose-lowering medications. As an unphased trial, this study offers a unique opportunity to contribute to foundational research that could lead to improved management strategies for prediabetes.

Will I have to stop taking my current medications?

Yes, if you are taking any glucose-lowering medications like metformin or sulfonylureas, you will need to stop taking them to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that insulin, the focus of this trial, is generally safe for people. Studies have found that using insulin, such as insulin glargine, to manage blood sugar over several years does not increase the risk of heart problems or cancer. Most people tolerate insulin well, and it effectively controls blood sugar. However, there is a small risk of low blood sugar (hypoglycemia), a known side effect. One study found that only about 1% of people using insulin experienced severe low blood sugar. Overall, insulin is considered safe, but like any medication, it carries some risks that participants should be aware of. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how insulin pulses can potentially alter the progression of prediabetes, a condition typically managed with lifestyle changes and medications like metformin. Unlike standard treatments that primarily focus on lowering blood sugar levels, this approach investigates how controlled insulin delivery can improve insulin sensitivity. By infusing Intralipid and heparin to induce acute insulin resistance, the trial aims to understand how the body’s response can be improved, offering new insights into managing prediabetes more effectively. This could pave the way for innovative strategies that go beyond current options, giving new hope to those at risk of developing diabetes.

What evidence suggests that insulin pulses could be an effective treatment for prediabetes?

This trial will compare the effects of insulin pulses with other interventions for managing prediabetes. Studies have shown that insulin effectively manages blood sugar levels in people with diabetes. For example, one study found that insulin lowered HbA1c, a measure of average blood sugar levels over time, from 9.6% to 8.6%, marking a significant improvement. Research also indicates that rapid-acting insulin can reduce the risk of low blood sugar episodes and improve blood sugar control after meals. Additionally, both Humulin R and Lantus, common types of insulin, have effectively controlled blood sugar levels. These findings suggest that insulin could help manage fasting blood sugar levels in people with prediabetes, potentially preventing complications. ^{6 7 8 9 10}

Who Is on the Research Team?

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with prediabetes, a condition where blood sugar levels are higher than normal but not high enough to be type 2 diabetes. Participants should have fasting hyperglycemia and be interested in how their body regulates glucose when they haven't eaten.

Inclusion Criteria

People with normal or impaired fasting glucose and normal or impaired glucose tolerance

Exclusion Criteria

I have symptoms from large or small vessel blood disease.

I am taking medication to lower my blood sugar.

I am not pregnant at the time of joining the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Intralipid and heparin or saline infusion to study insulin and glucagon interaction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Insulin

Trial Overview The study is looking at the effects of insulin and insulin pulses on blood sugar levels during fasting. It involves administering saline (saltwater solution), intralipid (a fat emulsion), and heparin (a medication that prevents blood clots) to see how these affect glucose control.

How Is the Trial Designed?

Group I: Intralipid and heparin Active Control 1 Intervention

Between 0600 (-180 min) and 1300 (240 min) Intralipid (20%, 0.011ml/kg/min; Baxter, Healthcare, Deerfield, IL) and heparin (200 units prime, 0.2 unit/kg/min continuous) will be infused to induce acute insulin resistance.

Group II: Saline Placebo Group 1 Intervention

Between 0600 (-180 min) and 1300 (240 min) saline will be infused

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+

Published Research Related to This Trial

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]

Insulin lispro, a fast-acting insulin analogue, provides effective postprandial blood glucose control in diabetic patients of all ages, showing similar or better results compared to regular human insulin without increasing the risk of hypoglycaemia.

The flexible administration of insulin lispro, either alone or as a premixture, allows for injections before or after meals, making it suitable for patients with unpredictable lifestyles and helping them achieve better glycaemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin lispro: a review of its use in the management of diabetes mellitus. Simpson, D., McCormack, PL., Keating, GM., et al.[2018]

In a meta-analysis of 22 randomized controlled trials involving 9691 patients with type 2 diabetes, basal analog (BA) insulin regimens showed similar efficacy to premix (PM) insulin regimens in reducing HbA1c and postprandial glucose levels, but with a significant reduction in fasting glucose levels.

BA regimens were associated with lower rates of total hypoglycemia and less weight gain compared to PM regimens, indicating a better safety profile for BA insulin in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Basal Analog Regimens in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hong, T., Lu, J., Zhang, P., et al.[2020]

In a study involving 112 children and adolescents with type 1 diabetes, the combination of ultrashort acting insulin aspart with detemir or glargine showed a significant decrease in HbA1c levels, indicating improved blood sugar control over 12 and 24 weeks.

The use of detemir and glargine significantly reduced the risk of hypoglycemia compared to traditional NPH-insulin, while maintaining a stable body mass index in the detemir group, suggesting a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. Prikhodina, OA., Surikova, SV., Girsh, YV.[2020]

Insulin detemir (Levemir) offers a long-acting and consistent insulin option for patients with type 1 or type 2 diabetes, providing a predictable effect with less variability in blood sugar control compared to NPH insulin.

It is at least as effective as NPH in managing overall blood sugar levels while reducing the risk of nocturnal hypoglycemia and causing less weight gain, making it a favorable choice for basal insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insulin detemir (Levemir)]. Scheen, AJ., Radermecker, RP., Philips, JC., et al.[2015]

In a study of 951 severely insulin-resistant type 2 diabetes patients, initiating Humulin R U-500 (U-500R) significantly improved treatment compliance and glycemic control, as evidenced by a reduction in HbA1c from 9.3% to 8.5%.

While U-500R improved overall insulin dosage and patient adherence, there was a modest increase in hypoglycemic events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Patterns and Outcomes, Before and After Humulin R U-500 Initiation, Among High-Dose Type 2 Diabetes Mellitus Patients in the United States. Hood, RC., Borra, S., Fan, L., et al.[2022]

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]

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]

Mixing the insulin analog lispro with NPH before injection does not reduce lispro's fast-acting profile, allowing for effective diabetes management without compromising its efficacy.

In a study with 12 healthy volunteers, the time to peak insulin levels was significantly shorter when lispro was mixed with NPH compared to regular insulin, indicating that this mixing strategy can help maintain optimal blood sugar control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The action profile of lispro is not blunted by mixing in the syringe with NPH insulin. Joseph, SE., Korzon-Burakowska, A., Woodworth, JR., et al.[2019]

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

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Treatment Patterns and Outcomes Before and After Humulin R ... The mean HbA1c decreased from pre- to post-initiation (9.6% vs 8.6%; p < 0.0001), and symptomatic hypoglycemia events per patient per year ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11099362/

Insulin therapy in type 2 diabetes: Insights into clinical efficacy ... It has become evident that rapid-acting insulin analogs yield superior outcomes in terms of reduced hypoglycemic events, improved postprandial blood glucose ...

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/0300060514529555

Clinical effectiveness of Novolin® 30R versus Lantus® ... Novolin 30R and Lantus combined with acarbose both had beneficial effects on blood glucose control and blood lipid levels in elderly patients with type 2 ...

4. withpower.com withpower.com/guides/humulin-r-vs-lantus-b75c

Humulin R vs Lantus | Power Both Humulin R (Regular insulin) and Lantus (Insulin glargine) are effective in managing blood glucose levels for people with diabetes, although they were ...

5. 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.

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Efficacy and safety of basal insulins in people with type 2 ... We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2638025/

Efficacy and safety of insulin analogues for the ... Rapid-and long-acting insulin analogues offer little benefit relative to conventional insulins in terms of glycemic control or reduced hypoglycemia.

8. 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.

9. diabetesjournals.org diabetesjournals.org/care/article/48/5/671/158024/The-Modern-Role-of-Basal-Insulin-in-Advancing

The Modern Role of Basal Insulin in Advancing Therapy in ... Severe hypoglycemia occurred in 1.0% of participants assigned to liraglutide vs. 1.3% of those allocated to Gla-100, while discontinuation rate ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0168822714003271

Efficacy and safety of basal insulin glargine 12 and 24 ... Early and sustained glycaemic benefits with a low-risk of hypoglycaemia are observed after initiation of insulin glargine in a pooled type 2 diabetes cohort.