Holding vs. Continuing Incretin-Based Therapies for Type 2 Diabetes

Not currently recruiting at 1 trial location

Overseen By Tilak Shah, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Must be taking: Incretin-based therapies

Disqualifiers: Gastroparesis, Achalasia, Foregut anatomy, others

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

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether stopping incretin-based diabetes medicines before an endoscopy reduces stomach issues during the procedure. It investigates if continuing or discontinuing medications such as Dulaglutide (Trulicity), Liraglutide (Victoza or Saxenda), Semaglutide (Ozempic, Wegovy, or Rybelsus), or Tirzepatide (Mounjaro or Zepbound) affects stomach content that could complicate the endoscopy. Individuals who have used these diabetes treatments for over a month and are planning an endoscopy might be suitable candidates. The trial focuses on reducing risks like leftover stomach content, which might lead to early procedure termination or more serious complications. As a Phase 4 trial, this research involves FDA-approved treatments and aims to enhance understanding of their benefits for more patients.

Will I have to stop taking my current medications?

The trial focuses on whether to hold incretin-based therapies before an endoscopy, so you might need to stop these specific medications temporarily. The protocol does not specify about other medications.

What is the safety track record for these treatments?

Research has shown that the treatments in this study—dulaglutide, liraglutide, semaglutide, and tirzepatide—are generally safe for people with type 2 diabetes.

Dulaglutide is usually well-tolerated, with common side effects like nausea and tiredness. Animal studies have raised concerns about thyroid tumors, but these have not been observed in humans.

Liraglutide has been tested in over 3,900 people and is considered safe, though a few cases of pancreatitis, or inflammation of the pancreas, have occurred. It also carries a rare risk of thyroid tumors.

Semaglutide has not revealed any new safety concerns and is generally well-tolerated. Serious low blood sugar (hypoglycemia) is rare, occurring in less than 1.5% of cases.

Tirzepatide is approved for type 2 diabetes and obesity and is considered safe based on real-world data, though animal studies have issued a warning about thyroid tumors.

Since these treatments are already FDA-approved for type 2 diabetes, their safety profiles are well-known. However, discussing any concerns about side effects with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike other treatments for type 2 diabetes, which typically need to be temporarily stopped before endoscopic procedures, this trial explores whether incretin-based therapies like Dulaglutide, Liraglutide, Semaglutide, and Tirzepatide can be safely continued. Researchers are excited about these treatments because they potentially offer better blood sugar control without the interruption, which is crucial for maintaining consistent management of type 2 diabetes. Incretin-based therapies work by enhancing insulin secretion and suppressing glucagon release, providing a unique approach to managing blood sugar levels compared to more traditional treatments. The trial could demonstrate that patients might not need to pause their medication, simplifying care and improving outcomes.

What evidence suggests that this trial's treatments could be effective for managing residual gastric volume in Type 2 Diabetes patients?

Incretin-based therapies, such as Dulaglutide, Liraglutide, Semaglutide, and Tirzepatide, effectively manage Type 2 diabetes. In this trial, participants will either continue their incretin-based medication as normal or pause their dose before an endoscopic procedure. Research consistently shows that Dulaglutide lowers HbA1c, a measure of long-term blood sugar levels. Liraglutide reduces blood sugar and aids in weight loss, which can help manage diabetes. Semaglutide lowers the risk of heart problems and improves overall health. Tirzepatide effectively aids in weight loss and reduces the risk of diabetes-related complications. These treatments help manage Type 2 diabetes and improve overall health outcomes. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with Type 2 Diabetes, Gastroparesis, and Obesity who are undergoing an upper endoscopy. Participants must be on incretin-based therapies like Dulaglutide, Semaglutide, Tirzepatide or Liraglutide.

Inclusion Criteria

I have been on a stable dose of incretin-based therapy for over a month.

I am scheduled for a specific stomach or digestive tract examination under anesthesia.

Exclusion Criteria

I have been diagnosed with achalasia.

Documented history of gastroparesis (based on a 4-hour solid-phase gastric emptying study)

Known gastric outlet obstruction or pre-procedure imaging suggestive of gastric outlet obstruction

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-procedure

Participants either continue or hold incretin-based therapy before the endoscopic procedure

1 week

1 visit (in-person)

Procedure

Endoscopic procedure is performed to assess residual gastric volume and other outcomes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dulaglutide
• Liraglutide
• Semaglutide
• Tirzepatide

Trial Overview The study aims to determine if stopping incretin-based medications before an upper endoscopy can reduce the risk of complications by decreasing residual gastric volume (RGV), which might interfere with the procedure.

How Is the Trial Designed?

Group I: Continue medication as normal prior to endoscopic procedure Active Control 4 Interventions

Does not withhold incretin therapy, maintains dose/frequency/duration of medication.

Group II: Hold dose prior to endoscopic procedure Active Control 1 Intervention

Withholds prior dose of incretin therapy per ASA guidance recommendations.

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?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

In a study of 126 overweight and obese patients with type 2 diabetes, dulaglutide (DU) showed a significant and sustained reduction in HbA1c levels over 18 months, with a mean decrease of -0.85% at 6 months, indicating its effectiveness as an add-on therapy to metformin.

Dulaglutide was associated with a higher percentage of patients achieving glycemic targets (HbA1c ≤ 7.0%) compared to liraglutide (LIRA) at 18 months, with 64.8% of DU patients reaching this target versus 42.6% for LIRA, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes. Mirabelli, M., Chiefari, E., Tocci, V., et al.[2021]

Saxagliptin, a DPP-4 inhibitor, significantly reduces HbA1c levels in type 2 diabetes patients when used alone or in combination with common medications like metformin and glyburide, based on a 24-week phase 3 clinical trial involving multiple studies.

The treatment was well tolerated, showed a low risk of hypoglycemia, and did not cause weight gain, making it a safe and effective option for managing blood sugar levels in type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of saxagliptin as monotherapy or adjunct therapy in the treatment of type 2 diabetes. Sharma, MD.[2021]

Liraglutide, a long-acting GLP-1 analog, has shown significant improvements in glycemic control in clinical trials lasting up to 1 year, reducing HbA1c levels by up to 1.5% and lowering both fasting and postprandial glucose concentrations.

The medication has a low risk of hypoglycemia due to its glucose-dependent action and is associated with weight loss and reductions in systolic blood pressure, although gastrointestinal side effects like nausea and vomiting are common initially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of liraglutide in the treatment of patients with type 2 diabetes. Deacon, CF.[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]

Saxagliptin significantly reduces glycosylated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM), with reductions ranging from -0.72% to -0.90% compared to -0.27% with placebo, based on data from 11 Phase III clinical trials.

Saxagliptin is well tolerated, with common side effects including upper respiratory infections and urinary tract infections, and it does not increase cardiovascular risk compared to other treatments, making it a safe option for managing T2DM, especially in combination with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. Kania, DS., Gonzalvo, JD., Weber, ZA.[2022]

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]

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 effectively lowers A1C levels and promotes weight loss in patients with type 2 diabetes by enhancing insulin secretion and reducing glucagon levels in a glucose-dependent manner, with A1C reductions ranging from -0.78% to -1.51%.

As a long-acting GLP-1 receptor agonist administered once a week, dulaglutide offers similar efficacy to liraglutide and exenatide, while its common side effects include nausea, vomiting, and diarrhea, making it a convenient treatment option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes. Thompson, AM., Trujillo, JM.[2022]

GLP-1-based therapies effectively improve blood sugar control with a low risk of causing hypoglycemia and also promote significant weight loss, making them beneficial for patients with diabetes.

The review highlights the need for personalized treatment options among various GLP-1 receptor agonists, as they differ in structure, pharmacological profiles, and safety, based on an extensive literature search of existing and upcoming medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes: Past, present, and future. Kalra, S., Baruah, MP., Sahay, RK., et al.[2022]

Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, are effective in managing type 2 diabetes mellitus (T2DM) by improving glycemic control and, in the case of GLP-1 agonists, promoting weight loss.

These medications are increasingly recommended as early treatment options due to their efficacy and favorable safety profiles, making them a significant focus in current diabetes management guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel incretin-based agents and practical regimens to meet needs and treatment goals of patients with type 2 diabetes mellitus. Garber, AJ.[2015]

GLP-1 analogues are more effective than DPP-4 inhibitors like sitagliptin in reducing HbA1C levels and body weight in patients with type 2 diabetes, based on a meta-analysis of four studies involving 1755 patients.

However, GLP-1 analogues are associated with a higher risk of gastrointestinal side effects, such as nausea and vomiting, compared to sitagliptin, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of GLP-1 analogues versus sitagliptin in the management of type 2 diabetes: systematic review and meta-analysis of head-to-head studies. Wang, T., Gou, Z., Wang, F., et al.[2022]

DPP-4 inhibitors like sitagliptin and vildagliptin effectively lower HbA1c levels by 0.5-1.1% without causing hypoglycemia or weight gain, making them a safe alternative for patients who cannot tolerate metformin.

GLP-1 analogues such as exenatide and liraglutide provide greater HbA1c reductions (0.8-1.7%) and promote weight loss (1.75-3.8 kg), but they are associated with gastrointestinal side effects that may lead to treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DPP-4 inhibitors and GLP-1 analogues: for whom? Which place for incretins in the management of type 2 diabetic patients? Halimi, S.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7324465/

Real-World Effectiveness of Dulaglutide in Patients with ... Studies consistently demonstrated that dulaglutide improved glycemic control by reducing HbA1c levels from pre-treatment. Furthermore, treatment ...

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

Clinical Trials: Lowereing A1C, Weight Change & CV Data In the AWARD-11 study, adults with type 2 diabetes taking Trulicity had a reduction in their A1C from the mean baseline of 8.6% at 36 weeks.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589936824000161

Comparative efficacy and safety of weekly dulaglutide ... Dulaglutide, particularly at higher doses, demonstrates superior efficacy in lowering hemoglobin A1C and reducing hypoglycemia risk compared to Icodec insulin.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204601

Once-Weekly Dulaglutide for the Treatment of Youths with ... Results from this double-blind, randomized, phase 3 trial showed that dulaglutide treatment was superior to placebo in reducing the glycated hemoglobin level ...

5. e-dmj.org e-dmj.org/journal/view.php?number=2809

Safety and Effectiveness of Dulaglutide in the Treatment ... Dulaglutide resulted in reductions in HbA1c, fasting blood glucose, and body weight. • Adverse events were consistent with the known safety ...

6. 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 ... To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin.

7. mayoclinic.org mayoclinic.org/drugs-supplements/dulaglutide-subcutaneous-route/description/drg-20122526

Dulaglutide (subcutaneous route) - Side effects & dosage Dulaglutide injection is used to treat type 2 diabetes mellitus. ... Safety and efficacy have not been established. Geriatric. Appropriate ...

8. trulicity.lilly.com trulicity.lilly.com/how-to-use/side-effects

Side Effects of Trulicity (dulaglutide) & How to Manage Them The most common adverse reactions experienced with Trulicity are nausea, diarrhea, vomiting, abdominal pain, decreased appetite, indigestion and fatigue.

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

Trulicity - accessdata.fda.gov WARNING: RISK OF THYROID C-CELL TUMORS. See full prescribing information for complete boxed warning. • Dulaglutide causes thyroid C-cell tumors in rats.