Study on Improving Blood Glucose Homeostasis With Dorzagliatin Tablets in the Treatment of Type 2 Diabetes Mellitus Patients With Moderate to Severe Chronic Renal Insufficiency

A Prospective, Randomized, Active-Controlled, Multicenter Clinical Study on Improving Blood Glucose Homeostasis With Dorzagliatin Tablets in the Treatment of Type 2 Diabetes Mellitus Patients With Moderate to Severe Chronic Renal Insufficiency

This study aims to evaluate whether dorzagliatin can improve glycemic homeostasis in patients with type 2 diabetes mellitus (T2DM) complicated by chronic renal insufficiency, and to compare the efficacy of dorzagliatin with linagliptin in improving glycemic control in patients with T2DM and moderate to severe chronic renal insufficiency (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m²).

This is a prospective, randomized, active-controlled, multicenter clinical study planned to enroll 206 eligible patients. After successful screening, patients will enter a 2-week run-in period consisting of diet and exercise control together with continuous glucose monitoring (CGM). Eligible patients will then be randomized to receive dorzagliatin 75 mg twice daily (BID) or linagliptin 5 mg once daily (QD) on top of background antihyperglycemic therapy. Basal insulin therapy will be standardized to insulin glargine U300 after treatment initiation. The treatment period will last 14 weeks, followed by a 1-week safety follow-up period.

This is a prospective, randomized, active-controlled, multicenter clinical study designed to enroll 206 eligible patients with T2DM complicated by moderate to severe chronic renal insufficiency.

Patients who pass screening will first enter a 2-week run-in period involving diet and exercise control and continuous glucose monitoring (CGM). Laboratory assessments and other relevant evaluations will be performed within 3 days prior to randomization.

At the randomization visit, eligibility will be reconfirmed according to the inclusion and exclusion criteria. Qualified patients will then be randomly assigned through a random number system to receive either dorzagliatin tablets 75 mg BID or linagliptin tablets 5 mg QD.

Both groups will receive study treatment on the basis of background antihyperglycemic therapy. Background antihyperglycemic therapy is defined as a stable glucose-lowering regimen used for at least 4 weeks prior to enrollment, consisting of basal insulin injection (excluding insulin-incretin combination preparations) and 0 to 2 oral antidiabetic drugs. Oral antidiabetic drugs are restricted to metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, alpha-glucosidase inhibitors (AGIs), meglitinides, and thiazolidinediones (TZDs). After treatment initiation, basal insulin will be standardized to insulin glargine U300 in all patients.

The treatment duration is 14 weeks. At the end of treatment, investigational medication will be discontinued, followed by a 1-week safety follow-up period.

Inclusion Criteria:

1. Aged 18 to 80 years.
2. Diagnosed with type 2 diabetes mellitus according to the 2026 American Diabetes Association (ADA) criteria or the 2024 Chinese Guidelines for the Prevention and Treatment of Diabetes.
3. Diagnosed with chronic renal insufficiency, with eGFR <45 mL/min/1.73 m² calculated using the Modification of Diet in Renal Disease (MDRD) equation, and not receiving maintenance dialysis.
4. HbA1c between 7.0% and 9.0%.
5. Receiving a stable antihyperglycemic treatment regimen for at least 4 weeks prior to enrollment. The regimen should include basal insulin injection (excluding insulin-incretin combination preparations) and 0 to 2 oral antidiabetic drugs. Oral antidiabetic drugs are limited to metformin, SGLT2 inhibitors, alpha-glucosidase inhibitors, meglitinides, and TZDs.
6. Written informed consent provided.

Exclusion Criteria:

1. Type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA), or other specific types of diabetes.
2. Diabetic ketoacidosis or hyperosmolar hyperglycemic state within the past 3 months.
3. Active liver disease (ALT/AST >3 × ULN) or liver cirrhosis (Child-Pugh class B or above).
4. Severe heart failure (NYHA class III-IV) or a history of acute coronary syndrome or stroke within the past 6 months.
5. Malignancy or life expectancy <6 months.
6. Pregnant or lactating women, or women of childbearing potential not using effective contraception.
7. Known allergy to dorzagliatin or any of its components.
8. Known allergy to linagliptin or any of its components.
9. Current participation in another interventional clinical trial.
10. Mental illness or cognitive impairment preventing compliance with study follow-up.
11. Severe gastrointestinal disease affecting drug absorption.
12. Current use of strong CYP3A4 inducers (e.g., rifampicin) or inhibitors (e.g., ketoconazole) that cannot be discontinued.
13. Severe hypertriglyceridemia (>5.7 mmol/L).
14. Dialysis for acute renal failure within 3 months before run-in, current dialysis, or need for/planned kidney transplantation within 12 months.
15. Use of corticosteroids or immunosuppressants within the past 6 months.
16. Current use of incretin-based therapies.