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

Not Applicable

Not yet recruiting

• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Interventions: Drug: Fixed-dose combination of SGLT2 inhibitor and thiazolidinedione; Drug: Control Group 1 Intervention - SGLT2 inhibitor monotherapy; Drug: Control Group 2 Intervention - Thiazolidinedione monotherapy; Drug: Background Therapy (All Groups) - Metformin

• Registration Number: NCT07057479
• Lead Sponsor: Eurofarma Laboratorios S.A.

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.

Detailed Description

This phase III clinical trial investigates a fixed-dose combination (FDC) of two established antidiabetic medications with complementary mechanisms of action: an SGLT2 inhibitor and a thiazolidinedione (TZD). The study aims to evaluate whether combining these medications in a single tablet provides superior glycemic control compared to either medication alone in patients with type 2 diabetes who are already on metformin therapy.

The SGLT2 inhibitor component lowers blood glucose by increasing urinary glucose excretion, while the TZD component improves insulin sensitivity. Previous studies have shown that these drug classes may offer complementary benefits for metabolic control and cardiovascular risk reduction. However, the TZD component has been associated with side effects including fluid retention and weight gain in some patients. This trial will assess whether the combination can maintain the therapeutic benefits of both drugs while potentially reducing TZD-related adverse effects.

The randomized, double-blind, double-dummy design compares three treatment arms: the FDC, SGLT2 inhibitor monotherapy, and TZD monotherapy. The primary endpoint is the change in HbA1c from baseline after 24 weeks of treatment. Secondary endpoints include measures of safety, tolerability, and additional metabolic parameters.

Participants will undergo regular monitoring including blood tests, physical examinations, and safety assessments throughout the study period. The trial includes specific protocols for detecting and managing potential side effects, particularly those related to fluid retention.

This study addresses an important clinical question regarding optimal treatment strategies for type 2 diabetes, particularly the potential advantages of fixed-dose combinations in simplifying treatment regimens while maintaining efficacy and safety. The results may provide evidence for a new therapeutic option that combines the established benefits of these two drug classes while potentially mitigating some limitations of monotherapy approaches.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-30
• Study First Submitted QC: 2025-06-30
• Last Update Submitted: 2025-06-30
• Study First Posted: 2025-07-09
• Last Update Posted: 2025-07-09
• Study Start: 2026-09-01
• Primary Completion: 2028-02
• Study Completion: 2028-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 408

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fixed-Dose Combination of SGLT2i /TZD + Metformin	Fixed-dose combination of SGLT2 inhibitor and thiazolidinedione	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.
Fixed-Dose Combination of SGLT2i /TZD + Metformin	Background Therapy (All Groups) - Metformin	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.
Control Group 2 - Thiazolidinedione + Metformin	Background Therapy (All Groups) - Metformin	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.
Control Group 1 - SGLT2 Inhibitor + Metformin	Control Group 1 Intervention - SGLT2 inhibitor monotherapy	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.
Control Group 1 - SGLT2 Inhibitor + Metformin	Background Therapy (All Groups) - Metformin	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.
Control Group 2 - Thiazolidinedione + Metformin	Control Group 2 Intervention - Thiazolidinedione monotherapy	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.

Primary Outcome Measures

Name	Time	Method
Change in glycated hemoglobin (HbA1c) from baseline to week 24	From baseline to week 24

Secondary Outcome Measures

Name	Time	Method
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
Proportion of participants achieving HbA1c <7.0% at week 24	At 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

Trial Locations

Locations (1)

Eurofarma Laboratórios S.A; 🇧🇷 Itapevi, São Paulo, Brazil