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Pancreatitis, ChronicPhase 2PEP-DMNCT06729996

Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis/Acute Pancreatitis Associated Diabetes Mellitus

A Phase 2 study testing Pioglitazone (PIO) and Empagliflozin (EMPA) in people with Pancreatitis, Chronic and Pancreatitis, Acute, run by Mayo Clinic at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to evaluate efficacy of pioglitazone (PIO) versus empagliflozin (EMPA) to improve glycemic control in people with Chronic Pancreatitis (CP) or Recurrent Acute Pancreatitis (RAP) or Acute Pancreatitis (AP) associated with Diabetes Mellitus (DM). Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Pioglitazone (PIO) and Empagliflozin (EMPA)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
3 sitesUnited States
Study dates
29 May 2025to 31 May 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18-80 years at the time of enrollment.
  • RAP or CP with DM diagnosed before or after CP diagnosis (Confirmed CP on imaging or RAP based on PROCEED study criteria, or acute pancreatitis followed by diabetes (AP-DM) and confirmed DM as per ADA criteria or clinically diagnosed with DM and on antihyperglycemic therapy)
  • Able to provide written informed consent and participate in longitudinal follow-up
  • A Stable retinal exam within 1 year prior to enrollment unless new onset diabetes was diagnosed within 6 months prior to study enrollment. If an eye exam within the past year is not available but the most recent exam is stable, a standard of care eye exam needs to be scheduled during the study period.
  • HbA1c level 6.5-10.5% at screening visit.
  • Current ongoing treatment with metformin and/or insulin and other antihyperglycemic medications will be accepted at screening. Patients will be willing to safely withdraw one or more study medication or mealtime insulin under the supervision of the study team by the time of screening. The patients clinical team will be informed promptly. Patients not on any antihyperglycemic medications are also eligible.
  • If on a GLP-1 medication (e.g., semaglutide [Ozempic, Wegovy, Rybelsus], liraglutide, dulaglutide, exenatide, tirzepatide, etc.), the patient must be on a stable dose for at least 3 months prior to enrollment, with stable weight status at the time of enrollment and the GLP-1 dose cannot be escalated during the study period.
  • Willing to perform blood glucose and ketone testing on study provided meters as per study protocol.

Who cannot join

  • Inability to take PIO or EMPA due to prior hypersensitivity or allergic reaction or current use of medications with potential for drug-drug interactions (Pioglitazone: Drug information - UpToDate, Empagliflozin: Drug information - UpToDate)
  • Patients on PIO or EMPA at the time of screening
  • Diagnosed with Type 1 Diabetes
  • Pregnancy or lactation in women (positive urine pregnancy test at screening will lead to exclusion)
  • History of bleeding disorders (e.g., Hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), von Willebrand disease, platelet disorders etc)
  • Presence of hepatic impairment, ALT >3 x ULN with no etiology known at the time of enrollment or any evidence of acute/chronic liver disease
Show all 17Show fewer
  • Ongoing treatment for any malignancy requiring systemic treatment (non-melanoma skin cancers treated in dermatologists' office would be acceptable)
  • Presence of osteoporosis without definitive treatment according to PI discretion.
  • Recent inflammatory illness within the 30 days preceding enrollment (e.g.: URTI, episode of AP, etc)
  • History of heart failure classified by NYHA as Class III or greater
  • History of kidney dysfunction classified by an eGFR of <30 mL/min/min
  • Participation in any clinical trial within 30 days before screening for an approved or non-approved investigational medical product.
  • Active alcohol dependence or chemical dependence including tobacco based on investigator discretion
  • On a ketogenic diet
  • Autoimmune pancreatitis, obstructive pancreatitis, and prior surgery of pancreas (Whipple procedure, total pancreatectomy, and distal pancreatectomy)
  • Any condition which could jeopardize participant safety as per investigator opinion, (hemolytic anemia limiting A1c reliability, any evidence of fluid overload, presence of Congestive heart failure etc).
  • Recent DKA or signs of decompensated diabetes in last 6 months or increased β hydroxybutyrate levels (>0.4 mmol/L) at screening.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ravinder Jeet Kaur, M.B.B.S contact

507-255-1455

Kaur.ravinder@mayo.edu

United States3 sites, 3 recruiting

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

    Shari Reynolds, BS, CCRP, 412-383-0570, reynoldssl2@upmc.edu

    Wanda Ferrara, MA, 412-648-7183, ferrarawa@upmc.edu

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15219

    Shari Reynolds, BS, CCRP, 412-383-0570, reynoldssl2@upmc.edu

    Dhiraj Yadav, MD, MPH

    Not yet recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Ravinder Jeet Kaur, M.B.B.S, 507-255-1455, kaur.ravinder@mayo.edu

    Chloe Miller, 507-255-0316, miller.chloe4@mayo.edu

    Recruiting

Other trials in United States

About this study

Official title: Randomized, Parallel Group, Dose Escalation Trial of Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis/Acute Pancreatitis Associated Diabetes Mellitus: The PEP-DM Trial

The purpose of this study is to evaluate efficacy of pioglitazone (PIO) versus empagliflozin (EMPA) to improve glycemic control in people with Chronic Pancreatitis (CP) or Recurrent Acute Pancreatitis (RAP) or Acute Pancreatitis (AP) associated with Diabetes Mellitus (DM). To evaluate mixed meal response in PIO versus EMPA group to better understand physiology of both therapies in CP-DM.

Read the detailed description

This trial will test the efficacy of PIO versus EMPA in improving glycemic control in CP-DM, RAP-DM and DM after one episode AP. The anticipated enrollment will consist of 40 subjects, age 18-80 years who have been diagnosed with CP or RAP or AP with DM, at two clinical sites in the United States. The primary objective is to evaluate the efficacy of PIO vs. EMPA to improve glycemic control in people with CP or RAP or AP associated with DM.

Being tested
Pioglitazone (PIO), Empagliflozin (EMPA)
Keywords
pancreatitis, diabetes, diabetes mellitus, empagliflozin, pioglitazone
Medical subject headings
Pancreatitis, Chronic, Pancreatitis, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pioglitazone (PIO)Drug

    Subjects will take 30 mg tablet, once daily in the morning, taken with or without food for 12 weeks and after 12 weeks dose will be escalated to 45 mg based on Hemoglobin A1c (HbA1c) levels (HbA1c >7.0% at 12 weeks, escalate the dose) once daily in the morning, taken with or without food till 24 weeks.

  • Empagliflozin (EMPA)Drug

    Subjects will start with 10 mg dose, once daily in the morning, taken with or without food for 12 weeks and after 12 weeks dose will be escalated to 25 mg based on Hemoglobin A1c (HbA1c) levels (HbA1c >7.0% at 12 weeks, escalate the dose) once daily in the morning, taken with or without food.

Study groups in NCT06729996
Study groupRoleWhat they receive
Pioglitazone (PIO)ExperimentalPIO (Actos) is a thiazolidinedione and an agonist for peroxisome proliferator activated receptor (PPAR) gamma indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 DM in multiple clinical settings. Its use has limitation for type 1 DM or for treatment of diabetic ketoacidosis. It is contraindicated to use in established NYHA class III or IV heart failure.
Receives: Drug: Pioglitazone (PIO)
Empagliflozin (EMPA)ExperimentalEMPA is a sodium-glucose co-transporter 2 inhibitor, FDA approved drug. It is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, to reduce the risk of cardiovascular death in adults with type 2 DM and established cardiovascular disease and as an adjunct to diet and exercise to improve glycemic control in adults with type 2 DM. It is not recommended in patients with type 1 DM. It may increase the risk of diabetic ketoacidosis. Not recommended for use to improve glycemic control in adults with type 2 DM with an eGFR less than 30mL/min/1.73m2.
Receives: Drug: Empagliflozin (EMPA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hemoglobin A1c (HbA1c)

    Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin, or glycates. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin. An HbA1C level below 5.7 percent is considered normal. Reported as percentage of glycated hemoglobin

    Measured: Baseline to 24 weeks

  2. Area under curve (AUC) for glucose

    Pre-post study difference in AUC for glucose

    Measured: Baseline to 24 weeks

  3. AUC for C-peptide

    Pre-post study difference in AUC for C-Peptide

    Measured: Baseline to 24 weeks

  4. AUC for Insulin

    Pre-post study difference in AUC for Insulin

    Measured: Baseline to 24 weeks

  5. AUC for glucagon

    Pre-post study difference in AUC for glucagon

    Measured: Baseline to 24 weeks

Secondary outcomes (14)

  1. Fasting plasma glucose

    Pre-post study difference in Fasting plasma glucose

    Measured: Baseline to 24 weeks

  2. Lean mass

    Pre-post study difference in lean mass

    Measured: Baseline to 24 weeks

  3. Fat mass

    Pre-post study difference in fat mass

    Measured: Baseline to 24 weeks

  4. Visceral fat

    Pre-post study difference in visceral fat

    Measured: Baseline to 24 weeks

  5. Fecal elastase

    Pre-post study difference in Fecal elastase (ELISA quantitative test, normal >200 mcg/g)

    Measured: Baseline to 24 weeks

  6. High Sensitivity C-Reactive Protein (Hs-CRP)

    Pre-post study difference in Hs-CRP

    Measured: Baseline to 24 weeks

  7. Total cholesterol, LDL, HDL and Triglyceride

    Pre-post study difference in Total cholesterol, LDL, HDL and Triglyceride

    Measured: Baseline to 24 weeks

  8. β-Hydroxybutyrate

    Pre-post study difference in β-Hydroxybutyrate

    Measured: Baseline to 24 weeks

  9. Body weight

    Pre-post study difference in body weight

    Measured: Baseline to 24 weeks

  10. Blood Pressure

    Pre-post study difference in Blood Pressure

    Measured: Baseline to 24 weeks

  11. Body Mass Index (BMI)

    Pre-post study difference in BMI

    Measured: Baseline to 24 weeks

  12. Patient-Reported Outcomes Measurement Information System - 29 Profile v2.1 (PROMIS-29 Profile v2.1)

    The PROMIS-29 Profile assesses following domains:

    • Physical function
    • Pain interference
    • Anxiety
    • Depression
    • Fatigue
    • Sleep disturbance
    • Ability to participate in social roles and activities

    PROMIS-29 is scored using T-scores. Higher T-scores indicate a higher level of the underlying construct.

    Each domain has a set of questions, typically 4 to 6 items, and responses are rated on a 5-point Likert scale (e.g., "Never," "Rarely," "Sometimes," "Often," "Always" or "Not at all," "A little bit," "Somewhat," etc.). The responses are then scored on a T-score scale (with a mean of 50 and a standard deviation of 10 in the general population).

    T-scores Interpretation:

    • A T-score of 50 is the average score for the general population.
    • T-scores above 50 indicate better functioning or less severe symptoms.
    • T-scores below 50 indicate worse functioning or more severe symptoms.

    Measured: Baseline to 24 weeks

  13. Insulin sensitivity

    Change in sensitivity from baseline vs 24 weeks (Homeostatic Model Assessment, Matsuda Index)

    Measured: Baseline to 24 weeks

  14. Beta cell function

    Change in Beta cell function from baseline vs 24 weeks using oral disposition index

    Measured: Baseline to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2024
  2. Study start29 May 2025
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06729996
Sponsor's protocol ID
24-003868
Acronym
PEP-DM
Status last verified
Jul 2026
First submitted
5 Dec 2024
Last updated
29 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pioglitazone (PIO) and Empagliflozin (EMPA) in people with Pancreatitis, Chronic and Pancreatitis, Acute, run by Mayo Clinic at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ravinder Jeet Kaur, M.B.B.S (507-255-1455, Kaur.ravinder@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hemoglobin A1c (HbA1c) (time frame: Baseline to 24 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06729996.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.

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