A Phase 2 interventional study of Pioglitazone (PIO) and Empagliflozin (EMPA) in Pancreatitis, Chronic, Pancreatitis, Acute and Diabetes Mellitus, sponsored by Mayo Clinic. Recruiting at 3 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-07-29.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
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.
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.
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.
a. 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.
Exclusion Criteria:
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)
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)
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.
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.
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
Time frame: Baseline to 24 weeks
Area under curve (AUC) for glucose
Pre-post study difference in AUC for glucose
Time frame: Baseline to 24 weeks
AUC for C-peptide
Pre-post study difference in AUC for C-Peptide
Time frame: Baseline to 24 weeks
AUC for Insulin
Pre-post study difference in AUC for Insulin
Time frame: Baseline to 24 weeks
AUC for glucagon
Pre-post study difference in AUC for glucagon
Time frame: Baseline to 24 weeks
Fasting plasma glucose
Pre-post study difference in Fasting plasma glucose
Time frame: Baseline to 24 weeks
Lean mass
Pre-post study difference in lean mass
Time frame: Baseline to 24 weeks
Fat mass
Pre-post study difference in fat mass
Time frame: Baseline to 24 weeks
Visceral fat
Pre-post study difference in visceral fat
Time frame: Baseline to 24 weeks
Fecal elastase
Pre-post study difference in Fecal elastase (ELISA quantitative test, normal \>200 mcg/g)
Time frame: Baseline to 24 weeks
High Sensitivity C-Reactive Protein (Hs-CRP)
Pre-post study difference in Hs-CRP
Time frame: Baseline to 24 weeks
Total cholesterol, LDL, HDL and Triglyceride
Pre-post study difference in Total cholesterol, LDL, HDL and Triglyceride
Time frame: Baseline to 24 weeks
β-Hydroxybutyrate
Pre-post study difference in β-Hydroxybutyrate
Time frame: Baseline to 24 weeks
Body weight
Pre-post study difference in body weight
Time frame: Baseline to 24 weeks
Blood Pressure
Pre-post study difference in Blood Pressure
Time frame: Baseline to 24 weeks
Body Mass Index (BMI)
Pre-post study difference in BMI
Time frame: Baseline to 24 weeks
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.
Time frame: Baseline to 24 weeks
Insulin sensitivity
Change in sensitivity from baseline vs 24 weeks (Homeostatic Model Assessment, Matsuda Index)
Time frame: Baseline to 24 weeks
Beta cell function
Change in Beta cell function from baseline vs 24 weeks using oral disposition index
Time frame: Baseline to 24 weeks
Ketosis
Percentage of participants experiencing Ketosis based on meter data
Time frame: Baseline to 24 weeks
Diabetic Ketoacidosis (DKA) events
Number of DKA events
Time frame: Baseline to 24 weeks
Insulin needs
Percentage of participants experiencing requirement for insulin
Time frame: Baseline to 24 weeks
Chronic pancreatitis exacerbation
Percentage of participants experiencing CP exacerbation
Time frame: Baseline to 24 weeks
Acute pancreatitis episodes
Percentage of participants experiencing AP episodes
Time frame: Baseline to 24 weeks
Exocrine pancreatic insufficiency
Percentage of participants experiencing incident exocrine pancreatic insufficiency
Time frame: Baseline to 24 weeks
Vitamin D
Decrease in vitamin D
Time frame: Baseline to 24 weeks
Bone fractures
Percentage of participants experiencing bone fractures
Time frame: Baseline to 24 weeks
Adverse events
Adverse events: Anemia, edema, urinary tract infection, Vaginal yeast infection
Time frame: Baseline to 24 weeks
Plan to share: No
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