Empagliflozin + Pioglitazone for Type 2 Diabetes

Overseen By Aurora Merovci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Sulfonylurea, Metformin

Must not be taking: GLP-1 RA, DPP-4i, TZD, Insulin

Disqualifiers: Proliferative retinopathy, eGFR < 60, others

Compensation: Varies

Number of Visits: 6

Duration: 10 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, empagliflozin and pioglitazone, to determine if they can better manage type 2 diabetes. Researchers aim to discover whether pioglitazone can block certain effects of empagliflozin, such as breaking down fats and increasing ketone production, which relate to blood sugar control. Individuals with type 2 diabetes who manage their condition with diet, certain medications, and maintain a relatively stable weight might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking diabetes research.

Will I have to stop taking my current medications?

If you are taking medications like sulfonylurea or metformin, you can continue them. However, if you are on medications like GLP-1 RA, DPP-4i, TZD, or insulin, you will need to stop them to participate in the trial.

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

Research has shown that empagliflozin and pioglitazone, when used separately, are generally safe for people with type 2 diabetes, with many patients tolerating these medications well.

Empagliflozin may cause side effects such as urinary tract infections and genital infections, though these are uncommon. Pioglitazone might lead to weight gain or swelling, and some individuals may experience mild stomach upset.

Studies suggest that these drugs can be safely combined with other treatments. Although specific data on using empagliflozin and pioglitazone together is lacking, both have been studied extensively enough to indicate general safety.

As this trial is in an early phase, it aims to understand safety more thoroughly. While there is strong evidence for safety, researchers remain cautious and continue to gather more data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Empagliflozin and Pioglitazone for treating Type 2 Diabetes because this combo could offer a dual-action approach that enhances blood sugar control. Unlike other treatments that often focus on just one mechanism, Empagliflozin helps the body get rid of excess glucose through urine, while Pioglitazone makes the body more sensitive to insulin. This combo might provide more comprehensive management of blood sugar levels, potentially leading to better outcomes for patients who struggle with existing options like metformin or insulin therapy.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes?

This trial will evaluate the effects of empagliflozin and pioglitazone, both separately and in combination, for managing blood sugar levels in people with type 2 diabetes. Studies have shown that empagliflozin helps the kidneys remove sugar from the body, while pioglitazone enhances insulin effectiveness. Research indicates that using these medications together can significantly improve blood sugar control. Specifically, one study found that about 33% of patients achieved healthier blood sugar levels after 24 weeks of treatment. These medications may also help improve conditions like fatty liver disease in people with type 2 diabetes. ^{1 2 4 5 6}

Who Is on the Research Team?

Ralph DeFronzo, MD

Principal Investigator

University of Texas Health Science Center San Antonio

Are You a Good Fit for This Trial?

Adults aged 30-75 with Type 2 Diabetes, stable weight, and good kidney function (eGFR > 60) can join. They should have a BMI of 21-45 kg/m2, controlled blood pressure (<145/85 mmHg), and HbA1c levels between 7.0-11%. Participants must be on stable statin therapy if applicable and not on certain diabetes medications like GLP-1 RA or insulin.

Inclusion Criteria

Patients with T2D

Hemoglobin A1C (HbA1c) = 7.0-11%

Blood Pressure (BP) < 145/85 mmHg

Exclusion Criteria

Women of childbearing potential are excluded unless they are taking/using appropriate contraceptive medications/devices

I am not currently taking GLP-1 RA, DPP-4i, TZD, or insulin.

I do not have proliferative retinopathy or kidney issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Study

Infusions of 3-3H-glucose and 14C-glycerol are started and continued to study end (2 PM). Baseline blood samples for various measurements are drawn.

1 day

1 visit (in-person)

Treatment

Participants are randomized into one of four groups for 10 weeks of treatment with empagliflozin, pioglitazone, or placebos. Interim visits every 1-2 weeks for monitoring.

10 weeks

5-10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Pioglitazone

Trial Overview The trial is testing how well Empagliflozin combined with Pioglitazone affects ketone production in T2D patients compared to each drug alone or placebos. It's looking at the drugs' impact on liver and fat tissue functions related to diabetes.

How Is the Trial Designed?

Group I: Empagliflozin plus Pioglitazone placebo Experimental Treatment 1 Intervention

Empagliflozin 25 mg/day plus pioglitazone placebo

Group II: Empagliflozin plus Pioglitazone Experimental Treatment 1 Intervention

Empagliflozin(25mg/day) plus pioglitazone (15/30 mg/d)

Group III: Empagliflozin placebo + pioglitazone placebo Experimental Treatment 1 Intervention

empagliflozin placebo plus pioglitazone placebo

Group IV: Pioglitazone plus Empagliflozin Placebo Placebo Group 1 Intervention

Pioglitazone, 15 mg/day, increased to 30 mg after 2 weeks plus empagliflozin placebo

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12515792/

Efficacy and safety of pioglitazone, empagliflozin and ... Furthermore, the proportions of patients who achieved an HbA1c level < 6.5% at week 24 were 32.76%, 33.33% and 27.87% for the empagliflozin, ...

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.70030

Efficacy and safety of pioglitazone, empagliflozin and ... The addition of empagliflozin, pioglitazone, or glimepiride to metformin and DPP-4 inhibitors significantly improved glycaemic control in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05942963?term=AREA%5BConditionSearch%5D(nafld)%20AND%20AREA%5BBasicSearch%5D(empagliflozin,%20pioglitazone)&rank=2

Efficacy of Empagliflozin and Pioglitazone in Diabetic ... This clinical trial will yield results about the therapeutic effect of combining pioglitazone with SGLT2i in people suffering from NAFLD associated with ...

4. brieflands.com brieflands.com/journals/amhsr/articles/144009

The Efficacy of Empagliflozin in Combination with ... It appears that both pioglitazone alone and pioglitazone combined with empagliflozin improve fatty liver disease in patients with type 2 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S014929182400198X

Efficacy and Safety of Pioglitazone Add-on in Patients with ... The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D)

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06571591

Study Details | NCT06571591 | Efficacy and Safety of ... Phase 3 study to assess the Efficacy and Safety of CT-L03-301 in Type 2 Diabetes Patients with Insufficient Glycemic Control with Metformin and Empagliflozin ...