Phase III Trial of SGLT2 Inhibitor and Thiazolidinedione Fixed-Dose Combination vs. Monotherapy in Type 2 Diabetes Patients on Metformin

NCT07057479 | Withdrawn Phase 3 DMC

• 1 other identifier: EF191
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is studying whether combining two commonly used diabetes medications into a single pill works better than taking them separately for people with type 2 diabetes who are already on metformin. Both medications work in different ways to lower blood sugar - one helps remove excess sugar through urine while the other helps the body use insulin better. The study has two main goals: To see if the combined pill controls blood sugar more effectively than either medication alone To check if combining them reduces common side effects like weight gain and swelling that can occur with one of the medications Participants will be randomly assigned to one of three groups: The new combination pill One of the standard diabetes medications alone The other standard diabetes medication alone All participants will take their assigned treatment daily and attend regular clinic visits for monitoring. Doctors will track blood sugar control, weight changes, and any side effects throughout the study period. This research could lead to a simpler treatment option that combines the benefits of both medications while potentially minimizing side effects. For people with diabetes who often need multiple medications, a combined pill might make treatment easier to manage while providing better blood sugar control.

Conditions

Type 2 Diabetes Mellitus (T2DM)

Keywords

Type 2 Diabetes Mellitus; T2DM; Fixed-dose combination; SGLT2 inhibitor; Thiazolidinedione; Dual therapy; Glycemic control; Insulin resistance; Randomized clinical trial; Phase III trial; Diabetes treatment; Oral antidiabetic drugs; Metformin adjunct therapy; HbA1c reduction; Cardiovascular risk factors; Renal protection; Diabetes complications; Monotherapy comparison; Drug combination efficacy; Diabetes management

Outcome Measures

Primary Outcomes (1)

• Change in glycated hemoglobin (HbA1c) from baseline to week 24

  From baseline to week 24

Secondary Outcomes (5)

• Proportion of participants achieving HbA1c <7.0% at week 24

  At week 24

• Change in fasting plasma glucose from baseline to week 24

  Baseline to week 24

• Incidence of adverse events (AEs) over 24 weeks

  Baseline to week 24

• Incidence of peripheral edema over 24 weeks

  Baseline to week 24

• Incidence of moderate/severe hypoglycemia (Level 2/3) over 24 weeks

  Baseline to week 24

Other Outcomes (1)

• Change in body weight from baseline to week 24

  Baseline to week 24

Study Arms (3)

Fixed-Dose Combination of SGLT2i /TZD + Metformin

EXPERIMENTAL

Participants receive a fixed-dose combination tablet containing two antidiabetic agents (an SGLT2 inhibitor and a thiazolidinedione) once daily, plus matching placebos for both comparator drugs to maintain blinding. All participants continue background metformin therapy (≥1000mg/day). Sample size: 136.

Drug: Fixed-dose combination of SGLT2 inhibitor and thiazolidinedione; Drug: Background Therapy (All Groups) - Metformin

Control Group 1 - SGLT2 Inhibitor + Metformin

ACTIVE COMPARATOR

Participants receive monotherapy with an SGLT2 inhibitor once daily, plus matching placebos for both the FDC and the thiazolidinedione comparator to maintain blinding. All participants continue background metformin therapy (≥1000mg/day). Sample size: 136.

Drug: Control Group 1 Intervention - SGLT2 inhibitor monotherapy; Drug: Background Therapy (All Groups) - Metformin

Control Group 2 - Thiazolidinedione + Metformin

ACTIVE COMPARATOR

Participants receive monotherapy with a thiazolidinedione once daily, plus matching placebos for both the FDC and the SGLT2 inhibitor comparator to maintain blinding. All participants continue background metformin therapy (≥1000mg/day). Sample size: 136.

Drug: Control Group 2 Intervention - Thiazolidinedione monotherapy; Drug: Background Therapy (All Groups) - Metformin

Interventions

Fixed-dose combination of SGLT2 inhibitor and thiazolidinedione DRUG

Oral fixed-dose combination tablet containing an SGLT2 inhibitor and a thiazolidinedione, administered once daily. Participants also receive matching placebos for both comparator drugs to maintain blinding. All participants continue background metformin therapy (≥1000mg/day).

Fixed-Dose Combination of SGLT2i /TZD + Metformin

Control Group 1 Intervention - SGLT2 inhibitor monotherapy DRUG

Oral tablet containing an SGLT2 inhibitor, administered once daily. Participants also receive matching placebos for both the fixed-dose combination and the thiazolidinedione comparator to maintain blinding. All participants continue background metformin therapy (≥1000mg/day). This represents standard monotherapy for comparison against the combination approach.

Control Group 1 - SGLT2 Inhibitor + Metformin

Control Group 2 Intervention - Thiazolidinedione monotherapy DRUG

Oral tablet containing a thiazolidinedione, administered once daily. Participants also receive matching placebos for both the fixed-dose combination and the SGLT2 inhibitor comparator to maintain blinding. All participants continue background metformin therapy (≥1000mg/day). This represents standard monotherapy for comparison against the combination approach.

Control Group 2 - Thiazolidinedione + Metformin

Background Therapy (All Groups) - Metformin DRUG

Extended-release metformin tablets (≥1000mg daily) continued as background therapy for all participants throughout the study duration.

Control Group 1 - SGLT2 Inhibitor + Metformin; Control Group 2 - Thiazolidinedione + Metformin; Fixed-Dose Combination of SGLT2i /TZD + Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Age ≥18 years
• Diagnosis of type 2 diabetes (T2DM)
• HbA1c 7.5-10% while on stable metformin monotherapy (≥1000 mg/day) for ≥12 weeks
• ≥80% adherence to run-in medication

You may not qualify if:

• Type 1 diabetes or other specific diabetes types (e.g., monogenic, pancreatic, or drug-induced)
• Severe hyperglycemia (≥270 mg/dL) or diabetic ketoacidosis in past 12 weeks
• Hypersensitivity to study drugs or excipients
• Pregnancy, lactation, or planning pregnancy
• Severe diabetic complications (proliferative retinopathy, severe neuropathy)
• Major cardiovascular events in past 12 weeks (e.g., myocardial infarction, heart failure NYHA III/IV)
• Uncontrolled hypertension (SBP \>180 mmHg or DBP \>110 mmHg)
• Moderate/severe renal impairment (eGFR \<45 mL/min/1.73m²)
• Liver disease (cirrhosis, active hepatitis)
• History of malignancy (except treated skin cancers) in past 5 years
• Use of non-metformin antidiabetics or weight-loss drugs in past 12 weeks

Sponsors & Collaborators

• Eurofarma Laboratorios S.A.: lead

Study Sites (1)

Eurofarma Laboratórios S.A

Itapevi, São Paulo, 06696-000, Brazil

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Diabetes Complications

Interventions

2,4-thiazolidinedione; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 9, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-06

Locations

BR (1)