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

Trial Summary

What is the purpose of this trial?

Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in 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.

What data supports the effectiveness of the drug Insulin for prediabetes?

Research shows that insulin analogues like Levemir and Lantus can effectively control blood sugar levels in people with diabetes, reducing the risk of low blood sugar episodes and maintaining stable glucose levels. These benefits suggest that similar insulin treatments might help manage blood sugar in prediabetes as well. ^{1 2 3 4 5}

Is insulin generally safe for humans?

Research shows that various types of insulin, including lispro, glargine, and detemir, have been studied for safety in people with diabetes. These studies found no significant differences in safety compared to regular human insulin, and they did not show increased risks of complications like kidney disease or cardiovascular issues. ^{1 3 6 7 8}

How does the drug insulin differ from other treatments for prediabetes?

Insulin pulses for prediabetes may offer a unique approach by using insulin analogues that have different action profiles, such as faster onset or longer duration, compared to regular human insulin. This could potentially provide more flexible and precise blood sugar control, mimicking the body's natural insulin response to food intake. ^{2 3 7 9 10}

Research Team

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. [2020]

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

Update on insulin analogues. [2019]

3. England 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. [2021]

4. Belgium pubmed.ncbi.nlm.nih.gov

[Insulin detemir (Levemir)]. [2015]

5. United States 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. [2022]

6. United States 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. [2020]

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

Lispro insulin as premeal therapy in type 1 diabetes: comparison with Humulin R. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety of insulin lispro: pooled data from clinical trials. [2019]

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

Insulin lispro: a review of its use in the management of diabetes mellitus. [2018]

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

The action profile of lispro is not blunted by mixing in the syringe with NPH insulin. [2019]