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

Recruiting at 1 trial location

Overseen By Tilak Shah, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

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)

Compensation: Varies

Number of Visits: 2

120 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess whether holding incretin-based therapy before endoscopy reduces the likelihood of clinically relevant Residual Gastric Volume (RGV). Primary Outcomes: * Residual gastric volume that precludes adequate endoscopic examination * Residual gastric volume that necessitates premature termination of the endoscopy procedure * Need for endotracheal intubation due to stomach contents. * Occurrence of aspiration events requiring extended observation/monitoring, unplanned therapeutics, and/or hospital admission Secondary Outcomes: * Presence of any solid food * Presence of moderate liquid content * Increased RGV(Residual Gastric Volume) defined as any amount of solid content or \> 0.8 mL/Kg of fluid content (measured from the aspiration/suction canister). * Differences in primary and secondary outcomes between different medications

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 data supports the effectiveness of the drug Dulaglutide for type 2 diabetes?

Dulaglutide has shown superior effectiveness compared to placebo and several other diabetes medications, such as metformin and insulin glargine, in lowering blood sugar levels and aiding weight loss. It is also comparable to liraglutide in reducing A1c (a measure of blood sugar control over time) and has a similar safety profile to other drugs in its class. ^{1 2 3 4 5}

Is it safe to use incretin-based therapies like dulaglutide and liraglutide for type 2 diabetes?

Incretin-based therapies such as dulaglutide and liraglutide are generally considered safe for treating type 2 diabetes, with the most common side effects being gastrointestinal issues like nausea and diarrhea. These side effects are usually more noticeable at the start of treatment and tend to decrease over time. ^{1 2 5 6 7}

How is the drug Dulaglutide different from other diabetes treatments?

Dulaglutide and similar drugs like Liraglutide, Semaglutide, and Tirzepatide are unique because they are GLP-1 receptor agonists, which means they mimic a hormone that helps control blood sugar and can also aid in weight loss. Unlike some other diabetes medications, these drugs are often injected and can provide more significant reductions in blood sugar levels and weight compared to oral medications. ^{8 9 10 11 12}

Eligibility Criteria

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.

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Advances in the treatment of type 2 diabetes: impact of dulaglutide. [2020]

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

Dulaglutide (Trulicity): The Third Once-Weekly GLP-1 Agonist. [2020]

3. England 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. [2022]

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

Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes: Past, present, and future. [2022]

6. Switzerland 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. [2021]

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

Potential of liraglutide in the treatment of patients with type 2 diabetes. [2022]

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

Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. [2022]

9. United States 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. [2022]

10. United States 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. [2015]

11. France 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? [2013]

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

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