Effects of Henagliflozin Proline and Metformin XR on Body Composition in Geriatric Patients With Newly Diagnosed T2DM

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.

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.