Effects of Henagliflozin Proline and Metformin XR on Body Composition in Geriatric Patients With Newly Diagnosed T2DM (HABIT-GEMs)

A Multicenter, Randomized, Parallel-group Clinical Study on the Effects of Henagliflozin Proline Tablets and Metformin Sustained-release Tablets on Body Composition in Geriatric Patients With Newly Diagnosed Type 2 Diabetes Mellitus

The goal of this clinical trial is to compare the effects of Henagliflozin Proline Tablets versus Metformin Extended-Release on body composition in elderly, drug-naïve patients with Type 2 Diabetes. The main questions it aims to answer are:

The effect of each treatment on the change in body composition, as measured by Appendicular Skeletal Muscle Index (ASMI), from baseline to 24 weeks.

The effect of each treatment on the change in HbA1c from baseline to 24 weeks. The comparative safety profile and other efficacy measures (e.g. fasting plasma glucose and additional body composition parameters) between the two treatments.

Researchers will compare the Henagliflozin Proline treatment group to the Metformin Extended-Release treatment group to evaluate potential differences in changes in muscle mass and metabolic parameters.

Participants will:

Be randomly assigned to one of the two treatment groups. Attend multiple clinic visits and telephone follow-ups over a 28-week period.

At clinic visits, undergo procedures including:

Physical examinations (height, weight, blood pressure, circumferences). Body composition analysis using bioelectrical impedance analysis (BIA). Physical function tests (handgrip strength, 5-times sit-to-stand test, 6-meter walk speed).

Blood and urine tests for efficacy and safety biomarkers. Dietary recording and exercise guidance. Start with a once-daily dose of either Henagliflozin Proline (5 mg) or Metformin XR (1000 mg), with a potential dose adjustment at Week 12.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Type 2
• Intervention / Treatment: Drug: Henagliflozin Proline Tablets treatment; Drug: Metformin XR treatment

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: bin lu; Phone Number: +86 18121186716; Email: lubinfd@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Voluntarily sign the informed consent form, be able to understand the procedures and methods of this study, and be willing to strictly comply with the clinical trial protocol to complete the study.

Aged between 60 and 85 years (inclusive) at the time of screening, regardless of gender.

Diagnosed with Type 2 Diabetes Mellitus according to WHO criteria, and not having used any glucose-lowering medications in the recent 3 months.

7.0% ≤ HbA1c ≤ 11.0% and Fasting Plasma Glucose ≤ 15 mmol/L. Body fat percentage: ≥25% for males, ≥30% for females.

Exclusion Criteria:

Known or suspected allergy to metformin, SGLT2 inhibitors, or excipients of the investigational product.

History of Type 1 Diabetes or other forms of insulin-dependent diabetes. Acute metabolic complications within the past 6 months, such as ketoacidosis, lactic acidosis, or hyperosmolar coma.

History of severe or recurrent hypoglycemic episodes. Presence of diabetes insipidus. Unstable thyroid function with treatment doses not stabilized within the past 3 months.

History of cardiovascular events within the past 6 months. Patients with uncontrolled hypertension or hypotension. Presence of clinical symptoms or recurrent urinary tract infections or genital infections.

History of osteoporosis, hematological diseases, malignancy, significant gastrointestinal disorders, fluid retention states, hypovolemia, or uncontrolled psychiatric disorders.

Systemic corticosteroid therapy for more than 7 days within the past 3 months. History of bariatric surgery within the past 12 months, use of weight-control medications within the past 3 months, or current participation in a weight-loss program not in the maintenance phase.

Gastrointestinal surgery that affects absorption within the past 3 months; long-term use of medications directly affecting gastrointestinal motility; or acute stress conditions such as surgery, infection, or hospitalization within the past 3 months.

Participation in any other drug clinical trial within the past 3 months. ALT or AST levels > 3 times the upper limit of normal; Hemoglobin ≤ 100 g/L; Renal impairment, defined as eGFR < 45 mL/min/1.73 m²; Fasting triglycerides ≥ 5.64 mmol/L.

History of diabetic retinopathy. Significantly abnormal 12-lead ECG. Any other condition deemed by the investigator as unsuitable for the subject's participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Henagliflozin Proline Tablets treatment group; Drug: Henagliflozin Proline Tablets treatment Start with a once-daily dose of either Henagliflozin Proline Tablets (5mg) ,with a potential dose adjustment at Week 12.	Drug: Henagliflozin Proline Tablets treatment; Start with a once-daily dose of either Henagliflozin Proline Tablets (5mg) , with a potential dose adjustment at Week 12.
Experimental: Metformin Sustained-release tablets treatment group; Start with a once-daily dose of either Metformin XR (1000mg), with a potential dose adjustment at Week 12.	Drug: Metformin XR treatment; Start with a once-daily dose of either Metformin XR (1000mg), with a potential dose adjustment at Week 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body composition (Appendicular Skeletal Muscle mass / Height² kg/m² weight in kilograms, height in meters) from baseline to Week 24.	Appendicular skeletal muscle mass index (ASMI, kg/m²) will be derived from bioelectrical impedance analysis (BIA) measurements. ASMI is calculated as appendicular skeletal muscle mass (ASM, kg) divided by height squared (m²). ASM will be estimated using a BIA device. Measurements will be performed at baseline (V0) and at week 24 (V6), following a standardised protocol that includes ≥4 hours of fasting. The ASM value will be generated by the device's integrated software.	from baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in appendicular skeletal muscle mass relative to body weight (ASM/BW) from baseline to Week 24.	ASM/BW is a unitless ratio (kg/kg) of appendicular skeletal muscle mass to total body weight. Both components will be measured using a bioelectrical impedance analysis (BIA) device, following a standardized protocol that includes participant fasting and rest prior to measurement. The ratio will be calculated from the raw BIA estimates of appendicular skeletal muscle mass and total body weight generated by the device software.	from baseline to Week 24
Change in HbA1c from baseline to Week 24.	HbA1c: Assessed from venous blood samples collected after a required fast. Analysis will be performed using a standardized, high-performance liquid chromatography (HPLC) method in a certified central laboratory at Baseline and Week 24.	from baseline to Week 24
Change in body fat percentage from baseline to Week 24.	Body fat percentage (BF%) is a unitless index calculated as estimated total body fat mass (in kg) divided by estimated total body weight (in kg), multiplied by 100%. Both fat mass and total body weight will be estimated by a bioelectrical impedance analysis (BIA) device, following a standardised pre-measurement protocol which includes fasting and rest.	from baseline to Week 24

Collaborators and Investigators

• Sponsor: Bin Lu
• Collaborators: Zhongnan Hospital; Fifth Affiliated Hospital, Sun Yat-Sen University; Second Affiliated Hospital of Soochow University; Shanxi Provincial People's Hospital; The Second Affiliated Hospital of Shandong First Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: January 1, 2026
• First Posted (Actual): January 7, 2026

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Therapeutics
• Other Study ID Numbers: 2025K268

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No