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

NCT06729996 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-003868
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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) 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.

Conditions

Pancreatitis, Chronic; Pancreatitis, Acute; Diabetes Mellitus

Keywords

pancreatitis; diabetes; diabetes mellitus; empagliflozin; pioglitazone

Outcome Measures

Primary Outcomes (5)

• 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

  Baseline to 24 weeks

• Area under curve (AUC) for glucose

  Pre-post study difference in AUC for glucose

  Baseline to 24 weeks

• AUC for C-peptide

  Pre-post study difference in AUC for C-Peptide

  Baseline to 24 weeks

• AUC for Insulin

  Pre-post study difference in AUC for Insulin

  Baseline to 24 weeks

• AUC for glucagon

  Pre-post study difference in AUC for glucagon

  Baseline to 24 weeks

Secondary Outcomes (14)

• Fasting plasma glucose

  Baseline to 24 weeks

• Lean mass

  Baseline to 24 weeks

• Fat mass

  Baseline to 24 weeks

• Visceral fat

  Baseline to 24 weeks

• Fecal elastase

  Baseline to 24 weeks

Other Outcomes (9)

• Ketosis

  Baseline to 24 weeks

• Diabetic Ketoacidosis (DKA) events

  Baseline to 24 weeks

• Insulin needs

  Baseline to 24 weeks

Study Arms (2)

Pioglitazone (PIO)

EXPERIMENTAL

PIO (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.

Drug: Pioglitazone (PIO)

Empagliflozin (EMPA)

EXPERIMENTAL

EMPA 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.

Drug: Empagliflozin (EMPA)

Interventions

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.

Pioglitazone (PIO)

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.

Empagliflozin (EMPA)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18-70 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, 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
• Stable last annual retinal exam within 1 year prior to enrollment.
• HbA1c level 7-10% at screening visit.
• Fasting plasma glucose \<220 mg/dL at screening visit.
• Not on any antihyperglycemic medication except Metformin
• Willing to perform blood glucose and ketone testing on study provided meters as per study protocol.

You may not qualify if:

• 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)
• Diagnosed with Type 1 Diabetes
• 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
• Ongoing treatment for any malignancy requiring systemic treatment (non-melanoma skin cancers treated in dermatologists' office would be acceptable)
• Presence of osteoporosis (the threshold of bone density value below the -2.5 SDS of T-score or presence of one or more fragility fractures), on electronic medical record.
• Recent inflammatory illness within the 30 days preceding enrollment (e.g.: URTI, episode of AP, etc)
• History of heart failure classified by New York Heart Association as Class III or greater
• History of kidney dysfunction classified by 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
• Any condition which could jeopardize participant safety as per investigator opinion, (hemolytic anemia limiting HbA1c 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• University of Pittsburgh Medical Center: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15219, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Pancreatitis, Chronic; Pancreatitis; Diabetes Mellitus

Interventions

Pioglitazone; empagliflozin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yogish Kudva

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Corey Kurek, BS

CONTACT

507-255-0316; Reid.Corey@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: December 12, 2024
• Study Start: May 29, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)