Clinical Trials

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.
• Participant willing to stop GLP-1 RA and DPP-4 medications for the duration of study and willing to allow optimization of other anti-hyperglycemic medications during trial.
• On Metformin or on no other antidiabetic medication.
• Patient keen to be in trial and on Sulfonylurea or on Insulin or any other anti-hyperglycemic therapies such as Meglitinides or alpha glucosidase inhibitors and safe to be in trial based on clinical consideration. Such patients may be enrolled after wash-out of such medications based on half-life considerations.
• Willing to drop ketogenic diet if on it.
• Willing to avoid excess alcohol consumption (Females drinking ≤1 drink per day or ≤7 per week and males drinking ≤2 drinks per day or ≤ 14 drinks per week)
• 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)
• 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 severe 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)
• 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 (>10 cigarette in a day or have a cigarette in the first half hour after waking up).
• Autoimmune pancreatitis, obstructive pancreatitis, and prior surgery of pancreas.
• 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/08/2024. Questions regarding updates should be directed to the study team contact.