Dulaglutide + Exercise for Type 1 Diabetes

(KML002 Trial)

Overseen By Kaitlin Love, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Virginia

Must be taking: Insulin

Must not be taking: Vasoactive medications

Disqualifiers: Pregnancy, Smoking, Microvascular complications, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 14 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how dulaglutide (Trulicity), combined with exercise, might help people with type 1 diabetes manage their condition more effectively. Researchers aim to determine if this combination can improve blood flow in muscles, potentially enhancing insulin effectiveness. Participants will either take dulaglutide, a placebo, or engage in high-intensity interval training on a stationary bike. Suitable candidates are adults who have had type 1 diabetes for over 5 years, use insulin, and face regular challenges in managing blood sugar levels. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in diabetes care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain blood pressure medications (like calcium channel blockers or ACE inhibitors).

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

Research has shown that dulaglutide is generally safe at doses used for type 2 diabetes. One study found that the 1.5 mg dose, like the one used in this trial, was well-tolerated. However, dulaglutide is not approved for type 1 diabetes, and individuals with serious stomach or intestinal issues should exercise caution.

Exercise is also part of the trial. Studies indicate that exercise is usually safe for people with diabetes, though there is a risk of low blood sugar (hypoglycemia) during exercise. Proper management and monitoring can help prevent this.

In summary, both treatments in the trial have demonstrated safety in similar situations, but discussing any personal concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dulaglutide for Type 1 Diabetes because it offers a unique approach compared to standard treatments, which typically focus on insulin regulation. Dulaglutide is a GLP-1 receptor agonist that works by enhancing the body's natural insulin secretion and slowing gastric emptying, potentially improving blood sugar control without the need for constant insulin adjustments. Additionally, it is administered as a weekly injection, which could be more convenient than the daily insulin injections required by many current therapies. This combination of improved glucose regulation and ease of use makes dulaglutide a promising option for individuals with Type 1 Diabetes.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

This trial will compare the effects of dulaglutide and exercise training on individuals with type 1 diabetes. Research has shown that dulaglutide, which participants in this trial may receive, can improve blood sugar control and aid weight loss in people with diabetes. One study found that a 1.5 mg dose of dulaglutide reduced A1C levels by an average of 1.5%. While dulaglutide benefits people with type 1 diabetes, some might experience stomach-related side effects.

Exercise training, another treatment option in this trial, boosts fitness and lowers insulin resistance in people with type 1 diabetes. It also helps reduce body weight and improve heart health, which are important for managing diabetes. Both dulaglutide and exercise offer benefits that support better diabetes management. ^{1 6 7 8 9}

Who Is on the Research Team?

Kaitlin Love, MD

Principal Investigator

Associate Professor - Endocrinology

Are You a Good Fit for This Trial?

Adults aged 18-40 with type 1 diabetes for over 5 years, managing it with insulin only, and a stable health condition can join. They must have an HbA1c level below 8.5% and a BMI between 19-34.9 kg/m^2. Those who've smoked recently, have musculoskeletal issues preventing exercise, severe diabetes complications or other unstable diseases cannot participate.

Inclusion Criteria

Your C-peptide level is less than 0.6 ng/ml.

Your body mass index (BMI) is between 19 and 34.9.

I use insulin for my diabetes, either through injections or a pump.

Exclusion Criteria

Your oxygen level is below 90% during screening.

You are allergic to perflutren, which is in the Definity© contrast.

I have diabetes with complications like heart disease, stroke, or nerve damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to 14 weeks of either dulaglutide, placebo, or exercise training

14 weeks

2 visits (in-person) at baseline and 14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dulaglutide
• Exercise Training

Trial Overview The trial is testing if Dulaglutide (a medication) and regular exercise improve blood flow in muscles by reducing stress on blood vessels in adults with type 1 diabetes. Participants will either receive Dulaglutide or a placebo while following an exercise routine to see which combination works best.

How Is the Trial Designed?

Group I: Exercise training Active Control 1 Intervention

Supervised high intensity interval training on a stationary bicycle will be conducted 3 days per week for 14 weeks. Participants will warm up at low intensity for 3 min then repeat 1-min bouts of 100% peak power output followed by 1-min recovery at 50 W. Training will start with 6 intervals per session, increasing by 2 intervals every 2 weeks. Sessions will end with a 10-min cool-down.

Group II: Dulaglutide Active Control 1 Intervention

Dulaglutide (0.75 mg/0.5 mL weekly for 2 weeks, then 1.5 mg/0.5 mL weekly for 12 weeks) subcutaneous injection

Group III: Placebo Placebo Group 1 Intervention

Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks

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

Approved in United States as Trulicity for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction in adults with established cardiovascular disease or multiple cardiovascular risk factors

Approved in European Union as Trulicity for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction in adults with established cardiovascular disease or multiple cardiovascular risk factors

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

A study involving 16 individuals with type 1 diabetes showed that reducing the bolus insulin dose (IAsp) by 50% before and after evening exercise significantly decreased the occurrence of hypoglycemia during and after exercise, enhancing glycemic safety.

Implementing this dose reduction strategy resulted in higher blood glucose levels during the acute post-exercise and nocturnal periods, indicating that careful insulin management can effectively minimize the risk of hypoglycemia in individuals with type 1 diabetes engaging in physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes. McCarthy, O., Deere, R., Churm, R., et al.[2021]

In a study involving nine adolescents with type 1 diabetes, it was found that glucose infusion rates needed to maintain stable blood sugar levels were higher during and shortly after exercise, indicating an increased risk of hypoglycemia immediately following physical activity.

The research revealed a biphasic pattern of glucose requirements, suggesting that adolescents may face both immediate and delayed risks of nocturnal hypoglycemia after exercising, highlighting the need for careful monitoring and management of glucose levels post-exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose requirements to maintain euglycemia after moderate-intensity afternoon exercise in adolescents with type 1 diabetes are increased in a biphasic manner. McMahon, SK., Ferreira, LD., Ratnam, N., et al.[2022]

In a study involving 10 adolescents with type 1 diabetes, moderate-intensity exercise performed at midday significantly increased the glucose infusion rate (GIR) needed to maintain normal blood sugar levels, indicating a heightened risk of hypoglycemia during and after exercise.

Unlike previous findings of a biphasic pattern of hypoglycemia risk after late-afternoon exercise, this study found that the risk of hypoglycemia remained elevated for several hours post-exercise without showing a second peak, suggesting different management strategies may be needed based on the timing of exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of midday moderate-intensity exercise on postexercise hypoglycemia risk in individuals with type 1 diabetes. Davey, RJ., Howe, W., Paramalingam, N., et al.[2013]

Dulaglutide (Trulicity®) is an effective once-weekly treatment for adults with type 2 diabetes, showing good tolerance and efficacy both as a standalone therapy and in combination with other diabetes medications, even in high-risk patients.

In the REWIND trial, dulaglutide significantly reduced the risk of major adverse cardiac events over a median follow-up of 5.4 years, highlighting its cardiovascular benefits alongside glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide: A Review in Type 2 Diabetes. Scott, LJ.[2021]

In a study involving 48 adults with type 1 diabetes, the use of mini-dose glucagon significantly reduced the incidence of exercise-associated hypoglycemia (EAH) during aerobic exercise, with only 12% experiencing hypoglycemia when using glucagon compared to 39% with a placebo.

Both glucagon treatment arms showed a lower incidence of hypoglycemia without significant differences in adverse events, suggesting that mini-dose glucagon is a safe and effective option for managing blood sugar levels during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Mini-Dose Ready-to-Use Liquid Glucagon on Preventing Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes. Aronson, R., Riddell, MC., Conoscenti, V., et al.[2023]

Exercise offers significant protective health benefits for individuals with type 1 diabetes, yet many do not meet recommended activity levels due to concerns about blood glucose management and hypoglycemia.

Advancements in glucose monitoring and insulin pump therapy have improved the ability of people with type 1 diabetes to engage in regular physical activity, and new training methods show promise in enhancing these benefits beyond just insulin regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why should people with type 1 diabetes exercise regularly? Codella, R., Terruzzi, I., Luzi, L.[2022]

Dulaglutide (Trulicity) is a once-weekly GLP-1 agonist that has been approved for the treatment of type 2 diabetes, providing a convenient dosing schedule for patients.

As the third GLP-1 agonist available, dulaglutide offers an effective option for managing blood sugar levels in individuals with type 2 diabetes, contributing to improved glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide (Trulicity): The Third Once-Weekly GLP-1 Agonist. Smith, LL., Mosley, JF., Parke, C., et al.[2020]

Dulaglutide (Trulicity™) is an effective once-weekly treatment for type 2 diabetes, showing significant improvements in glycemic control compared to oral metformin and non-inferiority to daily liraglutide in trials lasting up to 104 weeks.

It is generally well tolerated with a low risk of hypoglycemia, although gastrointestinal side effects like nausea and diarrhea are common; it also helps with weight loss, particularly at the higher dose of 1.5 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide: A Review in Type 2 Diabetes. Burness, CB., Scott, LJ.[2015]

Regular physical exercise can help individuals with Insulin-Dependent Diabetes Mellitus (IDDM) achieve better body weight management, improve self-image, and reduce cardiovascular risk factors, although its impact on long-term blood sugar control is still debated.

To safely participate in athletic activities, IDDM patients need to understand their metabolic responses to exercise and may require careful monitoring and adjustments to their insulin doses and nutrition plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes mellitus and exercise. Landry, GL., Allen, DB.[2006]

Dulaglutide (Trulicity®) is an effective once-weekly treatment for type 2 diabetes, showing greater glucose-lowering effects compared to metformin, sitagliptin, exenatide, and insulin glargine in Phase III clinical trials involving various patient backgrounds.

It is considered non-inferior to liraglutide, another GLP-1 receptor agonist, and is currently reimbursed in Belgium for patients who have not achieved adequate control with dual oral therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dulaglutide (Trulicity®), a new once-weekly agonist of glucagon-like peptide-1 receptors for type 2 diabetes]. Scheen, AJ.[2016]

Dulaglutide, a GLP-1 receptor agonist, has shown superior efficacy in lowering blood sugar levels compared to placebo and other diabetes medications, making it a strong option for treating type 2 diabetes.

The drug is administered once a week, has a favorable safety profile with common gastrointestinal side effects, and offers patient satisfaction similar to other GLP-1 receptor agonists, while also promoting weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of type 2 diabetes: impact of dulaglutide. Thompson, AM., Trujillo, JM.[2020]

Consuming 30 g of glucose before moderate-intensity exercise significantly increased blood glucose levels compared to not consuming glucose, indicating that pre-exercise glucose intake can help prevent hypoglycemia in individuals with type 1 diabetes using glargine/glulisine insulin.

Interspersing brief high-intensity intervals during moderate-intensity exercise also reduced the need for dextrose infusions to maintain blood glucose levels, suggesting that this strategy can be effective in managing exercise-induced hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose or intermittent high-intensity exercise in glargine/glulisine users with T1DM. Dubé, MC., Lavoie, C., Weisnagel, SJ.[2022]

The online educational tool ExT1D significantly reduced the total duration of exercise-related hypoglycaemia (ErH) by 71% in adults with Type 1 Diabetes, indicating its potential efficacy in managing hypoglycaemia during exercise.

Participants using ExT1D also reported increased confidence in preventing glucose drops during exercise, suggesting that the tool not only helps with safety but also encourages more active lifestyles for those with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An on-line support tool to reduce exercise-related hypoglycaemia and improve confidence to exercise in type 1 diabetes. Piotrowicz, AK., McGill, MJ., Overland, J., et al.[2022]

Maintaining blood glucose levels close to normal and keeping HbA1c under 7% are crucial for managing type 1 diabetes in children and adolescents, with successful control largely depending on quality diabetes education rather than just the number of daily insulin injections.

Fast-acting and long-acting insulin analogues can improve quality of life for patients, but they do not always lead to lower HbA1c levels, highlighting the importance of individualized insulin regimens and careful monitoring during physical activity to prevent complications like hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of type 1 diabetes (insulin, diet, sport): "Dorchy's recipes"]. Dorchy, H.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7896253/

Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus ... In conclusion, the AWARD-11 trial demonstrated glycemic and weight benefits for patients using 3- and 4.5-mg doses of dulaglutide once weekly, without ...

2. trulicity.lilly.com trulicity.lilly.com/hcp/efficacy-weight

Clinical Trials: Lowereing A1C, Weight Change & CV Data In a clinical study, the mean A1C reduction from baseline was 1.5% for the 1.5 mg dose (active control); 1.6% for the 3.0 mg dose; and 1.8% for the 4.5 mg dose.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666396121000054

An observational study evaluating effectiveness and ... Both drugs were associated to a weight loss of 5.63 kg (5.83% baseline weight) (Dulaglutide) and 7.6 kg (7.56%) (sc Semaglutide). Baseline age, ...

4. diabetesjournals.org diabetesjournals.org/care/article/38/12/2241/29030/Efficacy-and-Safety-of-Once-Weekly-Dulaglutide

Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin ... In phase 3 studies, dulaglutide demonstrated significant glycosylated hemoglobin A1c (HbA1c) reductions, with both fasting and postprandial ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31517629/

Efficacy and safety of dulaglutide in patients with absolute ... The results indicate that dulaglutide is effective in patients with T1DM or T2DM with absolute insulin deficiency, though gastrointestinal adverse events might ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/125469s036lbl.pdf

Trulicity - accessdata.fda.gov Not for treatment of type 1 diabetes mellitus (1). • Not recommended in patients with severe gastrointestinal disease, including severe gastroparesis (1, 5.6).

7. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/t/trulicityinj.pdf

New Zealand Data sheet 1. Trulicity (dulaglutide 1.5 mg/0.5 ... ... use. TRULICITY should not be used in patients with Type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Severe ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4665063/

Trulicity (Dulaglutide): A New GLP-1 Receptor Agonist Once ... Dulaglutide, a new, once-weekly subcutaneous injection became available as an adjunct to diet and exercise for adult patients with type 2 diabetes.

9. trulicity.lilly.com trulicity.lilly.com/

Once-Weekly Treatment for Type 2 Diabetes & Cardiovascular ... It is not known if Trulicity is safe and effective to lower blood sugar (glucose) in children under 10 years of age. Trulicity is given through an injection ...