Tirzepatide for Pediatric Type 2 Diabetes

(SURPASS-PEDS Trial)

No longer recruiting at 88 trial locations

Overseen By Steven Willi, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Metformin, Basal insulin

Must not be taking: Weight loss medications

Disqualifiers: Type 1 diabetes, Pancreatitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: 30 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of tirzepatide in children and teenagers with type 2 diabetes who are already taking metformin or basal insulin. Researchers seek to compare tirzepatide to a placebo (an inactive substance) in managing diabetes. Participants will receive either tirzepatide or a placebo through weekly injections. This trial is suitable for children and teens (ages 10 to below 18) with type 2 diabetes who have been managing it with stable doses of metformin or basal insulin for at least 90 days. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking diabetes treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your metformin and/or basal insulin dose is stable for at least 90 days before joining the study.

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

Research has shown that tirzepatide has been tested in children and teenagers with type 2 diabetes. In these studies, participants generally tolerated the drug well. They often experienced mild side effects like nausea, but these were usually manageable and short-lived. Tirzepatide significantly improved blood sugar levels. Its use in adults with diabetes suggests it is generally safe. While these findings are promising, discussing potential risks and benefits with a healthcare provider is essential before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for type 2 diabetes?

Researchers are excited about Tirzepatide for pediatric type 2 diabetes because it offers a novel approach by combining the actions of two hormones, GIP and GLP-1, that help regulate blood sugar levels. Unlike standard treatments like metformin or insulin, which primarily focus on reducing blood sugar, Tirzepatide targets multiple pathways to improve insulin sensitivity and reduce appetite. This multi-action approach has the potential to achieve better blood sugar control and weight management, which can be particularly beneficial for young patients managing type 2 diabetes.

What evidence suggests that tirzepatide might be an effective treatment for type 2 diabetes in children and teenagers?

Research shows that tirzepatide can significantly aid in managing type 2 diabetes. In this trial, participants will receive either tirzepatide at various dose levels or a placebo. One study found that children and teenagers with type 2 diabetes who took tirzepatide reduced their A1C levels (a measure of average blood sugar) by 2.2% on average. This reduction indicates better blood sugar control, crucial for managing diabetes. The treatment works by targeting two receptors that regulate blood sugar and appetite. These findings suggest that tirzepatide may be a promising option for those managing type 2 diabetes. ^{1 2 3 4 5}

Who Is on the Research Team?

1-877-CTLilly (1877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for children and teenagers aged 10 to under 18 with type 2 diabetes, who are already taking metformin or basal insulin. They should have a stable dose for at least 90 days prior to screening, an HbA1c level over 6.5% but not above 11%, weigh at least 50 kg (110 pounds), and have a BMI above the 85th percentile for their age and gender.

Inclusion Criteria

I manage my type 2 diabetes with diet, exercise, and stable doses of metformin or insulin.

I weigh at least 110 pounds and my BMI is in the top 15% for my age and gender.

I am between 10 and 17 years old.

Exclusion Criteria

I have had pancreatitis before.

I am not pregnant, breastfeeding, or planning to become pregnant.

I have had diabetic ketoacidosis or hyperosmolar syndrome after being diagnosed with type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Tirzepatide or placebo by weekly SC injection, with dose adjustments every four weeks

30 weeks

14 visits (in-person), 6 visits (phone)

Open-label extension

Participants continue to receive Tirzepatide at the last dose level

30 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tirzepatide

Trial Overview The study tests the safety and effectiveness of Tirzepatide in two different doses compared to a placebo in young patients with type 2 diabetes inadequately controlled by metformin or basal insulin. It involves around sixty weeks of participation, including up to fourteen clinic visits and six phone calls.

How Is the Trial Designed?

Group I: Tirzepatide Dose 2 Experimental Treatment 1 Intervention

Double-Blind: Participants receive Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 2 is reached. Open-Label: Participants will continue to receive Tirzepatide at the last dose level

Group II: Tirzepatide Dose 1 Experimental Treatment 1 Intervention

Double-Blind: Participants receive Tirzepatide by weekly subcutaneous (SC) injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached. Open-Label: Participants will continue to receive Tirzepatide at the last dose level

Group III: Placebo Placebo Group 2 Interventions

Double-Blind: Participants receive placebo during the 30-week double-blind period. Open-Label: Participants will switch to Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

CGRP antagonists, including second-generation gepants like rimegepant and ubrogepant, have been shown to be effective for both acute and preventive treatment of migraines, with no increased mortality risks associated with their use.

While serious adverse events were reported, they were likely unrelated to the medications, indicating a favorable safety profile; however, ongoing monitoring for long-term side effects, particularly in elderly populations, is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gepants for Acute and Preventive Migraine Treatment: A Narrative Review. Rissardo, JP., Caprara, ALF.[2022]

Tirzepatide, a medication for type 2 diabetes, shows a dose-dependent increase in gastrointestinal adverse events (AEs), with nausea and diarrhea being the most common, affecting up to 49% of participants at the highest dose (15 mg).

Despite the gastrointestinal side effects, serious adverse events like severe hypoglycemia and acute pancreatitis are rare (≤ 1%), indicating that tirzepatide is generally safe for use in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. Mishra, R., Raj, R., Elshimy, G., et al.[2023]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

Migraine is a prevalent issue among children and adolescents, leading to significant disability, yet there are limited evidence-based treatment options compared to adults.

This review highlights the need for evaluating newer migraine therapies, such as onabotulinumtoxinA and CGRP monoclonal antibodies, in pediatric populations, as current treatments do not work for all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond the Guidelines: A Narrative Review of Treatments on the Horizon for Migraine in Children and Adolescents. VanderPluym, JH., Victorio, MCC., Oakley, CB., et al.[2023]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed greater improvements in glucose control and weight loss compared to the GLP-1 receptor agonist dulaglutide in a study involving 316 participants with type 2 diabetes.

The improvements in insulin sensitivity and beta-cell function with tirzepatide were only partially linked to weight loss, indicating that its dual receptor action provides unique mechanisms for better glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. Thomas, MK., Nikooienejad, A., Bray, R., et al.[2022]

In a phase 3 trial involving 636 Japanese adults with type 2 diabetes, tirzepatide demonstrated superior efficacy in lowering HbA1c levels compared to dulaglutide, with reductions of -2.4% to -2.8% for tirzepatide versus -1.3% for dulaglutide after 52 weeks.

Tirzepatide also led to significant weight loss, with reductions ranging from -5.8 kg to -10.7 kg depending on the dose, while dulaglutide resulted in only a -0.5 kg reduction, indicating its potential as an effective treatment for both glycemic control and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Inagaki, N., Takeuchi, M., Oura, T., et al.[2022]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40975112/

a randomised, double-blind, placebo-controlled, phase 3 trial Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05260021

NCT05260021 | A Study to Evaluate Tirzepatide ... The purpose of this study is to learn more about the safety and efficacy of tirzepatide compared to placebo in children or teenagers with type 2 diabetes.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822209

Clinical Outcomes of Tirzepatide or GLP-1 Receptor ... Treatment with tirzepatide was associated with significantly lower hazards of all-cause mortality and major adverse cardiovascular and kidney events compared ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362501774X

Articles Efficacy and safety of tirzepatide in children and ... 3, 4 In the TODAY study, 50% of participants with youth-onset type 2 diabetes developed a microvascular complication by year 9 of follow-up and 80% by year 15 ...

5. prnewswire.com prnewswire.com/news-releases/lillys-mounjaro-tirzepatide-a-gipglp-1-dual-receptor-agonist-reduced-a1c-by-an-average-of-2-2-in-a-phase-3-trial-of-children-and-adolescents-with-type-2-diabetes-302559576.html

Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual receptor ... In SURPASS-PEDS, Mounjaro met the primary and all key secondary endpoints at 30 weeks and showed sustained improvement in glycemic control ...