Sitagliptin for Type 2 Diabetes with Genetic Mutation

Overseen By Jessica R Wilson, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Insulin, GLP-1 agonists

Disqualifiers: Pregnancy, Type 1 diabetes, 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 tests sitagliptin, a medication, to determine if it lowers blood sugar levels in people with type 2 diabetes who have a specific genetic mutation. Researchers aim to find out if sitagliptin can reduce certain enzyme activities and improve blood sugar control. Participants will take both the medication and a placebo (inactive pill) at different times. Suitable candidates typically have type 2 diabetes and a genetic mutation affecting an enzyme called DPP4. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

Do I have to stop taking my current medications for the trial?

You cannot participate if you are using insulin, a GLP-1 agonist, or a DPP4 inhibitor. Other oral diabetes medications are allowed only if matched with controls. The protocol does not specify about other medications, so it's best to discuss with the study team.

What is the safety track record for these treatments?

Research has shown that taking 100 mg of sitagliptin daily is generally safe for people with type 2 diabetes. In a study involving over 10,000 patients, sitagliptin did not increase the risk of serious side effects, such as major heart issues, cancer, or pancreas inflammation. These findings suggest that sitagliptin is a safe option for managing type 2 diabetes. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for type 2 diabetes, which often include lifestyle changes, metformin, sulfonylureas, and insulin, sitagliptin offers a unique approach by specifically targeting the DPP-4 enzyme. This mechanism increases the levels of incretin hormones, which help regulate insulin and blood sugar levels more effectively. Researchers are excited about sitagliptin because it can potentially provide better blood sugar control with fewer side effects, especially for individuals with certain genetic mutations that affect their response to traditional therapies. Plus, sitagliptin is taken as a once-daily pill, which can be more convenient for patients compared to some other diabetes treatments.

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

This trial will compare the effects of sitagliptin with a placebo in managing Type 2 diabetes. Studies have shown that sitagliptin effectively helps the body use insulin better and manage blood sugar levels. This is particularly important for individuals with certain genetic traits affecting the DPP4 enzyme, as sitagliptin targets this enzyme. Unlike some other treatments, sitagliptin does not increase the risk of low blood sugar (hypoglycemia) or cause weight gain. Additionally, it may help reduce inflammation and organ damage related to diabetes. Overall, sitagliptin is a proven option for effectively managing Type 2 diabetes. ^{6 7 8 9 10}

Who Is on the Research Team?

Jessica R Wilson, MD, MS

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with likely decreased DPP4 enzyme activity due to genetics, and who are part of the Penn Medicine Biobank. Participants should match controls in age, gender, race, BMI, hypertension and diabetes status, renal function, and certain medication use. Exclusions include severe kidney or liver disease, significant heart conditions like heart transplants, insulin or other specific diabetes drug use (except metformin), recent acute illness or hospitalization.

Inclusion Criteria

I match the study's required age, gender, race, BMI, and health conditions.

You are part of the Penn Medicine Biobank and are open to being contacted for future research studies.

I am between 18 and 70 years old and likely have low DPP4 levels.

Exclusion Criteria

I have a severe lung condition.

Inability to comprehend study procedures

I have Type 1 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Sitagliptin

Participants receive sitagliptin 100 mg/d for 7 days

7 days

1 visit (in-person) on day 7

Washout

A 4-week washout period between treatment phases

4 weeks

Treatment - Placebo

Participants receive placebo daily for 7 days

7 days

1 visit (in-person) on day 7

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo Oral Tablet
• Sitagliptin 100mg

Trial Overview The trial tests if Sitagliptin (a DPP4 inhibitor) affects blood sugar levels after a meal differently in people with genetic variations that decrease DPP4 enzyme activity compared to a placebo. It also looks at whether it changes levels of substances broken down by DPP4 in these individuals versus matched controls without the genetic variation.

How Is the Trial Designed?

Group I: Crossover BA Experimental Treatment 2 Interventions

Subjects in arm B will first receive sitagliptin 100mg/d for 7 days in the first intervention followed by placebo for 7 days in the crossover intervention.

Group II: Crossover AB Experimental Treatment 2 Interventions

Subjects in arm A will first receive placebo daily for 7 days in the first intervention followed by sitagliptin 100mg/d for 7 days in the crossover intervention.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00813228

Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) ... Sitagliptin has been shown by Merck to be safe and effective with no overt immuno-toxicities. However, several lines of evidence suggest that DPP-4 inhibitors ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9191836/

Genome-Wide Transcriptome Analysis in Type 2 Diabetes ... Sitagliptin has the following advantages: it does not increase the risk of hypoglycemia, it does not cause an increase in body weight, it does ...

3. withpower.com withpower.com/trial/phase-4-diabetes-mellitus-type-2-7-2020-baaf9

Sitagliptin for Type 2 Diabetes with Genetic Mutation This trial is for adults aged 18-70 with likely decreased DPP4 enzyme activity due to genetics, and who are part of the Penn Medicine Biobank. Participants ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0925443925000717

Pathogenesis and therapeutic effect of sitagliptin in ... Sitagliptin treatment reduced organ injury, hyperglycemia, inflammation, and fibrinolytic activity while improving insulin resistance and glucose metabolism.

5. journals.lww.com journals.lww.com/md-journal/fulltext/2019/09060/efficacy_and_hypoglycemic_risk_of_sitagliptin_in.54.aspx

Efficacy and hypoglycemic risk of sitagliptin in obese ... Our study found that for obese/overweight patients, sitagliptin exerts a less potent effect on the decrease in HbA 1C, FPG, PPG, and body weight than GLP-1 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3687098/

Safety and Tolerability of Sitagliptin in Type 2 Diabetes Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events, malignancy, or pancreatitis. Conclusion. In this ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3161395/

Safety and tolerability of sitagliptin in clinical studies: a pooled ... In this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical ...

8. merck.com merck.com/news/merck-stands-behind-the-safety-profile-of-januvia-sitagliptin/

Merck Stands Behind the Safety Profile of JANUVIA® ... We are confident in the safety profile of sitagliptin, which is an important medicine to help adults with type 2 diabetes lower their blood sugar levels.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00813228

Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) ... Sitagliptin is now being tested in individuals with new-onset T1D to determine whether it may help to preserve beta cell function. Because T1D is a disease in ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02791490?term=ristaben&checkSpell=&rank=2

A Study of the Safety and Efficacy of Sitagliptin Addition ... This trial is designed to evaluate, in adult participants with Type 2 diabetes mellitus (T2DM) and inadequate glycemic control on sub-maximal metformin ...