Oral Semaglutide for Type 2 Diabetes

(GLUCOSE-MGH Trial)

Overseen By Josephine Li

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must not be taking: Diabetes medications, Glucocorticoids

Disqualifiers: Intestinal malabsorption, Thyroid cancer, 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: 3

Duration: 14 days

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how genetic differences affect reactions to oral semaglutide, a medication for treating type 2 diabetes. Participants will take the medication daily for two weeks and undergo blood tests to assess how their bodies process sugars and fats after consuming a specific breakfast. This trial suits individuals with normal to slightly high blood sugar levels (fasting glucose between 100-125 mg/dL) who are not currently taking diabetes medication or other medicines that affect blood sugar. As a Phase 4 trial, oral semaglutide has already received FDA approval and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications for diabetes or those that affect blood sugar levels, like glucocorticoids, growth hormone, or fluoroquinolones, to participate in this trial.

What is the safety track record for oral semaglutide?

Research has shown that oral semaglutide, a medication for type 2 diabetes, is generally safe and well-tolerated. Studies have found it effectively lowers blood sugar levels. However, some people may experience stomach-related side effects, such as nausea or an upset stomach. About 27% of patients reported these side effects, and around 10.8% had to stop taking it due to these issues. Despite this, the FDA has approved the treatment, indicating a strong safety record for treating type 2 diabetes. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Oral Semaglutide is unique because it offers a convenient oral administration, unlike most other treatments for type 2 diabetes which typically require injections, like insulin or injectable GLP-1 receptor agonists. This makes it easier for patients to maintain their treatment regimen. Additionally, Semaglutide is a GLP-1 receptor agonist, which not only helps control blood sugar levels but also promotes weight loss, a beneficial effect for many individuals with type 2 diabetes. Researchers are excited about the potential to improve adherence and overall patient outcomes with this more accessible and multifaceted approach.

What is the effectiveness track record for oral semaglutide in treating type 2 diabetes?

Research has shown that oral semaglutide, the treatment under study in this trial, effectively treats type 2 diabetes. Studies indicate it significantly lowers blood sugar levels, reducing HbA1c (a measure of blood sugar control) by about 1.1%. It also aids in weight loss, with patients losing around 3.5 kg and experiencing a decrease in body mass index (BMI). The FDA has approved this medication, confirming its effectiveness in managing type 2 diabetes. Overall, oral semaglutide offers a reliable option for improving both blood sugar and weight management. ^{2 3 6 7 8}

Who Is on the Research Team?

Josephine Li, MD

Principal Investigator

MGH

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 who can consent and have blood sugar levels indicating they are between normal health and pre-diabetes. It's not suitable for pregnant individuals or those outside the age range.

Inclusion Criteria

Able/willing to give consent

I am a male or a non-pregnant female.

My blood sugar levels are between 100-125 mg/dL, indicating pre-diabetes.

Exclusion Criteria

Dietary restrictions preventing consumption of a MMTT

I have a history of digestive system issues like celiac or gallbladder disease.

I or my family have a history of medullary thyroid cancer or MEN2.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Baseline Assessment

Participants undergo a mixed meal tolerance test and baseline measurements are taken

1 day

1 visit (in-person)

Treatment

Participants take 7 mg of oral semaglutide once daily for 14 days

14 days

Daily self-administration

Post-Treatment Assessment

Participants undergo a second mixed meal tolerance test and final measurements are taken

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Semaglutide

Trial Overview The study tests how genetic differences affect responses to Rybelsus, a diabetes/obesity drug, by analyzing blood factors after a standard meal before and after two weeks of taking the drug.

How Is the Trial Designed?

Group I: GLUCOSE-MGH Study Experimental Treatment 2 Interventions

Day 1: Mixed meal tolerance test Day 3-15: 7 mg oral semaglutide, once daily Day 16: 1 dose of 7 mg oral semaglutide, Mixed meal tolerance test in the presence of semaglutide

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Oral semaglutide 14 mg has been shown to be effective in lowering HbA1c levels and body weight in patients with type 2 diabetes mellitus, outperforming placebo and other active comparators in multiple phase 3 trials.

The most common side effects of oral semaglutide are gastrointestinal issues, which often lead to discontinuation of the medication, highlighting the need for monitoring patient tolerance during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide in type 2 diabetes mellitus: Comprehensive review, critical appraisal and clinical consideration of its use in India. Singh, AK., Singh, R., Misra, A.[2022]

Oral semaglutide, the first oral GLP-1 receptor agonist for type 2 diabetes, demonstrated the lowest cost of control for achieving key treatment targets compared to empagliflozin, sitagliptin, and liraglutide, based on data from the PIONEER clinical trials.

For endpoints like achieving HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide was significantly more cost-effective, with savings of up to $15,036 compared to other medications, indicating its potential for better economic value in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Cost Per Patient Achieving Treatment Targets with Oral Semaglutide: A Short-Term Cost-Effectiveness Analysis in the United States. Hunt, B., Hansen, BB., Ericsson, Å., et al.[2022]

In a retrospective study of 782 patients using oral semaglutide for type 2 diabetes, there was a significant average reduction in HbA1c levels of -0.9% after about 6 months, indicating effective glycaemic control.

The study highlighted a treatment gap, as 37% of patients remained on the initial 3 mg dose instead of increasing to the recommended 7 mg after 30 days, suggesting that some patients may not be receiving optimal dosing for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights into the early use of oral semaglutide in routine clinical practice: The IGNITE study. Aroda, VR., Faurby, M., Lophaven, S., et al.[2021]

In a phase 3b trial involving 1606 adults with type 2 diabetes, higher doses of oral semaglutide (25 mg and 50 mg) significantly reduced HbA1c levels more than the approved 14 mg dose, with reductions of -1.8 and -2.0 percentage points respectively.

The study found that while gastrointestinal side effects were more common with the higher doses, no new safety concerns were identified, and all reported deaths were deemed unrelated to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. Aroda, VR., Aberle, J., Bardtrum, L., et al.[2023]

In a study of 32 patients with Type 2 Diabetes over 26 weeks, oral semaglutide significantly reduced body fat and improved metabolic parameters, including liver health indicators.

The treatment preserved muscle mass while decreasing visceral fat, leading to a better muscle-to-fat ratio, which is beneficial for overall health in T2D patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study. Volpe, S., Lisco, G., Fanelli, M., et al.[2023]

Oral semaglutide, the first oral GLP-1 receptor agonist, significantly reduced HbA1c levels by 1.1-1.5% and body weight by up to 5 kg in clinical trials, outperforming other diabetes medications like empagliflozin and liraglutide.

The most common side effects were mild-to-moderate gastrointestinal issues, primarily transient nausea, indicating a generally safe profile for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Will oral semaglutide be a game-changer in the management of type 2 diabetes in primary care? Seidu, S., Mellbin, L., Kaiser, M., et al.[2021]

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

Oral semaglutide, a GLP-1 analogue, was found to be safe and well-tolerated in two clinical trials involving 135 healthy males and 23 males with type 2 diabetes, with most adverse events being mild and primarily gastrointestinal.

The pharmacokinetics showed that semaglutide exposure increased with higher doses and was consistent across healthy individuals and those with type 2 diabetes, supporting its suitability for once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes. Granhall, C., Donsmark, M., Blicher, TM., et al.[2020]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Oral semaglutide, a new GLP-1 receptor agonist, significantly reduced glycated hemoglobin (HbA1c) levels by up to 1.4% after 26 weeks compared to placebo, indicating its efficacy in managing blood sugar levels in type 2 diabetes patients.

The treatment also led to greater body weight reductions compared to placebo and sitagliptin, with mild-to-moderate gastrointestinal side effects that typically decreased over time, suggesting it is a safe option with a low risk of severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo. Lavernia, F., Blonde, L.[2022]

A total of 5,442 cases of gastrointestinal adverse events (AEs) associated with semaglutide were identified, with 45 signals detected, indicating a range of gastrointestinal issues, including 17 new and unexpected signals.

The study found that patient age and body weight were significant factors influencing the severity of gastrointestinal AEs, with a median time-to-onset of 23 days for strong signals, suggesting that while risks exist, they may decrease over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. Shu, Y., He, X., Wu, P., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11355440/

Oral Semaglutide in Type 2 Diabetes: Clinical–Metabolic ... This study demonstrated that a six-month treatment with oral semaglutide at a daily dose of 14 mg significantly improves GC, weight management, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1871402124000857

Efficacy and safety of oral semaglutide in type 2 diabetes This retrospective cohort study showed −1.1 % HbA1c reduction, −3.5 kg weight loss, −1.1 kg/m2 BMI decrease (p < 0.001 for all), and 32.4 % of patients achieved ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39616020/

Real-world Evidence on Oral Semaglutide for the ... In real-world settings, oral semaglutide provided significant glycemic (median HbA1c reduction at 6 months of 1%) and weight (median body weight ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1901118

Oral Semaglutide and Cardiovascular Outcomes in ... In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo.

5. diabetesresearchclinicalpractice.com diabetesresearchclinicalpractice.com/article/S0168-8227(24)00838-6/fulltext

Focus on patients with type 2 diabetes older than 75 years Data on the efficacy of oral semaglutide (OS) in elderly patients with type 2 diabetes are still lacking. This study evaluates the effectiveness ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6897065/

Oral Semaglutide In The Management Of Type 2 Diabetes Oral semaglutide has already been proven to be efficacious at lowering glucose levels and it is generally well tolerated. Moreover, ...

7. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15431

Real-world effectiveness and safety of oral semaglutide in ... Oral semaglutide was effective and safe for an unselected population, with one-third reporting weight loss >10% and about two-thirds achieving ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213182Orig1s000MedR.pdf

213182Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov safety of oral semaglutide in subjects with type 2 diabetes. Primary objective. To confirm that treatment with oral semaglutide does not ...