Henagliflozin added to insulin to reduce blood sugar swings and age-related immune changes in type 2 diabetes

The Effects of Henagliflozin on glucOse fLuctuation and Immunosenescence in Type 2 Diabetes pAtients on Insulin therapY: a Multicenter, Randomized, Double-blind, Placebo-controlled Study (the HOLIDYA Study)

Phase 4 Interventional Xinhua Hospital, Shanghai Jiao Tong University School of Medicine · NCT06818851

This will test whether adding henagliflozin to insulin in adults 50–70 with type 2 diabetes reduces daily blood sugar swings and improves age-related immune function.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment64 (estimated)
Ages50 Years to 70 Years
SexAll
SponsorXinhua Hospital, Shanghai Jiao Tong University School of Medicine Academic / other
Locations1 site (Shanghai, Shanghai Municipality)
Trial IDNCT06818851 on ClinicalTrials.gov

What this trial studies

Adults aged 50–70 with type 2 diabetes and poor control on basal insulin will receive either oral henagliflozin or placebo daily for 16 weeks alongside their usual insulin regimen. Participants will have weekly follow-up calls for insulin dose guidance and will wear a continuous glucose monitor for 7 days at baseline and again at the end of the study to measure glycemic variability (e.g., MAGE). Blood samples will be collected to measure markers of immunosenescence and routine safety labs. Outcomes will compare changes in glucose variability and immune-aging markers between the henagliflozin and placebo groups.

Who should consider this trial

Good fit: Ideal candidates are adults 50–70 years old with type 2 diabetes for at least 6 months who have poor control (HbA1c >8%) while on basal insulin and have normal C-peptide levels.

Not a fit: People with well-controlled diabetes, recent use of SGLT2 or GLP-1 drugs, known allergy to SGLT2 inhibitors, or those unable to attend visits in Shanghai are unlikely to receive benefit from participation.

Why it matters

Potential benefit: If successful, henagliflozin could reduce harmful blood sugar swings and slow age-related declines in immune function, potentially lowering cardiovascular and infection risks.

How similar studies have performed: Other SGLT2 inhibitors have been shown to lower glucose and reduce cardiovascular risk and some data suggest reduced glycemic variability, but effects on immunosenescence are largely novel and unproven.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Diagnosed with type 2 diabetes mellitus (T2DM) for at least 6 months based on the 1999 WHO criteria.

  * Age between 50 and 70 years at the time of signing the informed consent form (inclusive).
  * Poor glycemic control despite treatment with basal insulin or insulin degludec/aspart (with or without oral antidiabetic drugs) within the 3 months prior to screening.
  * HbA1c level above 8%.
  * BMI ≥ 20 kg/m².
  * C-peptide levels within the normal reference range.
  * Able to maintain stable dietary and exercise habits during the study.
  * Capable of understanding the study procedures and methods, willing to strictly comply with the clinical trial protocol, and voluntarily sign the informed consent form.

Exclusion Criteria:

* Patients considered by the investigator to have potential allergies to the components of the study drug or drugs of the same class.

  * Use of SGLT2 inhibitors or GLP-1 receptor agonists within 3 months prior to screening.
  * Adjustments to antidiabetic treatment regimens within 3 months prior to screening.
  * Hospitalization due to acute coronary syndrome (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or unstable angina), percutaneous coronary intervention, or cardiac surgery within 30 days prior to the screening visit.
  * Volume depletion.
  * Chronic (\>2 weeks) systemic glucocorticoid therapy or use of glucocorticoids within 4 weeks prior to screening (except for topical, intraocular, intranasal, or inhaled administration).
  * Pregnancy, lactation, or plans for pregnancy within the next 6 months.
  * Persistently elevated serum transaminase levels (more than 3 times the upper limit of normal).
  * Renal impairment (estimated glomerular filtration rate \[eGFR\] \< 45 mL/min/1.73 m²).
  * History of malignant tumors.
  * Presence of acute complications (e.g., ketoacidosis, diabetic ketoacidosis, lactic acidosis, or hyperosmolar coma).
  * Systemic autoimmune diseases, such as systemic lupus erythematosus.
  * Clinically significant urinary tract infections and/or genital infections, or a history of recurrent urinary tract and/or genital infections.
  * Any other factors deemed by the investigator to potentially affect the efficacy or safety evaluation of the study.
  * Participation in other clinical trials and receipt of investigational drugs within 3 months prior to screening.

Where this trial is running

Shanghai, Shanghai Municipality

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Diabetes Mellitus, Type 2Sodium-glucose cotransporter 2glycemic variabilityimmunosenescence
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.