Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis Associated Diabetes Mellitus (PEP-DM)

Mayo Clinic

Status and phase: Enrolling; Phase 2

Conditions: Diabetes Mellitus; Pancreatitis, Acute; Pancreatitis, Chronic

Treatments: Drug: Empagliflozin (EMPA); Drug: Pioglitazone (PIO)

Study type: Interventional

Funder types: Other

Identifiers

NCT06729996

24-003868

Details and patient eligibility

About

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.

Full description

This trial will test the efficacy of PIO versus EMPA in improving glycemic control in CP-DM. The anticipated enrollment will consist of 40 subjects, age 18-70 years who have been diagnosed with CP or RAP 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 associated with DM.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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
• 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
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Pioglitazone (PIO)

Experimental group

Description:

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.

Treatment:

Drug: Pioglitazone (PIO)

Empagliflozin (EMPA)

Experimental group

Description:

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.

Treatment:

Drug: Empagliflozin (EMPA)