Pioglitazone vs Empagliflozin for Diabetes

(PEP-DM Trial)

Recruiting at 1 trial location

Overseen By Corey Kurek, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Metformin

Disqualifiers: Type 1 diabetes, Pregnancy, Bleeding disorders, Hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two medications, Pioglitazone and Empagliflozin, in managing blood sugar for individuals with diabetes linked to chronic or recurrent pancreatitis. The study aims to better understand the impact of these treatments on pancreatitis-related diabetes. Suitable candidates for this trial have chronic or recurrent pancreatitis and diabetes, manage their diabetes with Metformin, and are willing to monitor their blood glucose and ketone levels during the study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants are not on any antihyperglycemic medication except Metformin. If you are taking other diabetes medications, you may need to stop them to join the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that empagliflozin is generally safe for people with type 2 diabetes. Studies involving over 12,500 adults found no increased risk of amputations or bone fractures. However, it may raise the risk of diabetic ketoacidosis, a serious condition where the body produces too much acid in the blood. It is not recommended for individuals with type 1 diabetes or severe kidney problems.

The FDA has approved pioglitazone for managing type 2 diabetes. It helps control blood sugar when combined with diet and exercise. However, using pioglitazone for more than a year may increase the risk of bladder cancer. It is unsuitable for those with severe heart failure. Both treatments have been well-studied, providing a good understanding of their safety for treating type 2 diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these diabetes treatments because they offer unique mechanisms compared to standard options like metformin or sulfonylureas. Empagliflozin is a standout as it inhibits sodium-glucose co-transporter 2 (SGLT2), which not only helps control blood sugar but also reduces the risk of cardiovascular death and heart failure hospitalization in patients with type 2 diabetes. Pioglitazone, on the other hand, is a thiazolidinedione that activates PPAR gamma, improving insulin sensitivity, which is crucial for glycemic control. These distinct mechanisms provide potential benefits beyond what current treatments offer, making them promising options for comprehensive management of type 2 diabetes.

What evidence suggests that this trial's treatments could be effective for diabetes associated with chronic or recurrent acute pancreatitis?

This trial will compare the effects of empagliflozin and pioglitazone in managing type 2 diabetes. Studies have shown that empagliflozin, one of the treatments in this trial, lowers A1C levels, a measure of long-term blood sugar control, in adults with type 2 diabetes. It also reduces the risk of heart-related death and the need for hospital visits due to heart failure in these patients. Meanwhile, research indicates that pioglitazone, the other treatment option in this trial, effectively improves blood sugar control in type 2 diabetes and is linked to a lower risk of death from any cause. Both treatments show promise for managing diabetes, especially when heart health is a concern. ^{6 7 8 9 10}

Who Is on the Research Team?

Yogish Kudva, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with diabetes that's related to chronic or recurrent acute pancreatitis. Participants should have a history of these conditions and need better blood sugar control.

Inclusion Criteria

Able to provide written informed consent and participate in longitudinal follow-up

Fasting plasma glucose <220 mg/dL at screening visit

I am only taking Metformin for my blood sugar.

Exclusion Criteria

I am not on any systemic treatment for cancer, except for non-melanoma skin cancers.

I have a history of bleeding disorders like Hemophilia or von Willebrand disease.

My kidney function is very low.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Pioglitazone or Empagliflozin to improve glycemic control in CP-DM

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Pioglitazone

Trial Overview The study aims to compare the effectiveness of two diabetes medications, Pioglitazone (PIO) and Empagliflozin (EMPA), in managing blood sugar levels in patients with pancreatitis-associated diabetes.

How Is the Trial Designed?

Group I: Pioglitazone (PIO) Experimental Treatment 1 Intervention

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.

Group II: Empagliflozin (EMPA) Experimental Treatment 1 Intervention

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.

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Published Research Related to This Trial

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

In a study of 78 patients with uncontrolled type 2 diabetes, dapagliflozin showed the most significant reduction in HbA1c levels after 24 months, with a mean change of -1.05%, compared to sitagliptin (-0.81%) and lobeglitazone (-1.08%).

Dapagliflozin also improved body composition by decreasing whole body fat percentage and increasing muscle percentage, while sitagliptin and lobeglitazone led to increases in body fat, suggesting dapagliflozin may be a better option for patients looking to improve their body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. Hong, JH., Moon, JS., Seong, K., et al.[2023]

In a study involving 4,866 patients with type 2 diabetes, the combination of metformin and pioglitazone (Competact) significantly improved glycemic control, as evidenced by a reduction in HbA1c from 7.8% to 7.0% after 4 months of treatment.

The therapy also led to significant improvements in blood pressure and lipid profiles, while not affecting body mass index (BMI), indicating its efficacy in managing multiple aspects of diabetes without weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Competact, a fixed combination of pioglitazone and metformin, improves metabolic markers in type 2 diabetes patients with insufficient glycemic control by metformin alone--results from a post-marketing surveillance trial under daily routine conditions. Schöndorf, T., Karagiannis, E., Posseldt, RE., et al.[2022]

Pioglitazone is an effective second-line therapy for type 2 diabetes, offering strong blood sugar control, a lower risk of cardiovascular issues, and improved liver health compared to other treatments.

While gliptins like sitagliptin and vildagliptin also lower blood sugar effectively, they lack long-term safety data and are more expensive, making pioglitazone a more favorable option in many cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of therapeutic efficiency and costs (experience in Bulgaria) of oral antidiabetic therapies based on glitazones and gliptins. Filipova, EP., Uzunova, KH., Vekov, TY.[2022]

The study found that a generic empagliflozin tablet is bioequivalent to the brand-named Jardiance® in terms of key pharmacokinetic parameters, indicating that both formulations can be expected to have similar efficacy and safety profiles in healthy individuals.

Consumption of high-fat food did not affect the pharmacokinetics of empagliflozin, suggesting that it can be taken with or without food without impacting its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of a generic empagliflozin tablet versus a brand-named product and the food effects in healthy Chinese subjects. Li, X., Liu, L., Deng, Y., et al.[2021]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. Chen, G., Zhang, D., Du, A., et al.[2021]

Empagliflozin, an SGLT2 inhibitor, is effective in improving blood sugar control in adults with type 2 diabetes, especially when metformin is not suitable.

In addition to managing diabetes, empagliflozin also aims to reduce cardiovascular risks associated with the condition, highlighting its dual role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

In a study of 268 patients with inadequately controlled type 2 diabetes, adding empagliflozin (25 mg/day) significantly reduced HbA1c and fasting plasma glucose levels compared to insulin glargine after 24 weeks.

Empagliflozin also led to notable improvements in body weight and systolic blood pressure, while having fewer hypoglycemic events compared to insulin, indicating it is a safe and effective add-on therapy for glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of empagliflozin-based quadruple therapy compared with insulin glargine-based therapy in patients with inadequately controlled type 2 diabetes: An observational study in clinical practice. Ku, EJ., Lee, DH., Jeon, HJ., et al.[2022]

A new combination tablet of empagliflozin and sitagliptin was successfully developed using a direct compression method, showing excellent in-vitro performance with a disintegration time of 5.32 minutes and high drug release rates (89.05% for empagliflozin and 93.76% for sitagliptin).

In vivo testing on mice demonstrated that this combination significantly reduced fasting blood glucose and cholesterol levels, achieving results comparable to metformin, indicating its potential as an effective treatment for type-2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design expert software assisted development and evaluation of empagliflozin and sitagliptin combination tablet with improved in-vivo anti-diabetic activities. Hossain, MS., Jahan, S., Al Rezwan Rahman, S., et al.[2023]

Citations

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Effectiveness and safety of empagliflozin: final results from ... Empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy.

2. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/t2d/efficacy

T2D Efficacy Data | Jardiance® (empagliflozin) tablets Explore the efficacy and clinical trial data of JARDIANCE in reducing A1C levels for adults with type 2 diabetes. See Safety, Prescribing Info, & Med Guide.

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Empagliflozin, Cardiovascular Outcomes, and Mortality in ... In conclusion, patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin had significantly lower rates of ...

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Empagliflozin and Clinical Outcomes in Patients With Type ... Empagliflozin improved clinical outcomes and reduced mortality in vulnerable patients with type 2 diabetes mellitus, established cardiovascular disease, and ...

5. valueinhealthjournal.com valueinhealthjournal.com/article/S1098-3015(17)30791-X/fulltext

Cost-Effectiveness of Empagliflozin (Jardiance®) In The ... According to effectiveness results, empagliflozin plus SoC was associated with longer survival (20.06 LY vs 16.72 LY with placebo plus SoC) with an incremental ...

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Safety Profile for T2D | Jardiance® (empagliflozin) tablets Explore the safety and tolerability data shown across multiple trials for JARDIANCE in adults with type 2 diabetes. See Safety, Prescription Info, & Med Guide.

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Pooled Safety and Tolerability Analysis of Empagliflozin in ... This comprehensive analysis confirms that both empagliflozin 10 mg and 25 mg are well tolerated in patients with T2DM, reinforcing the established clinical ...

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Safety of Empagliflozin in Patients With Type 2 Diabetes and ... Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of ...

9. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/jardiance-empagliflozin-analysis-reinforces-established-safety-profile

Jardiance® (empagliflozin) T2D Analysis on Safety Profile Analysis of 12,500 adults with type 2 diabetes from 19 studies showed amputations and fractures were not increased with Jardiance compared ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/204629s040lbl.pdf

JARDIANCE® (empagliflozin tablets) - accessdata.fda.gov The safety profile of pediatric patients treated with. JARDIANCE was similar to that observed in adults with type 2 diabetes mellitus, with the exception of.