Metformin-Dapagliflozin Effects on IGF-1 in Male T2DM With MASLD

NCT07778719 | Not Yet Recruiting DMC

• 1 other identifier: 2026JW001-20
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 3-month, single-center, prospective, randomized, parallel-controlled, open-label trial investigating the effects of metformin combined with dapagliflozin on serum IGF-1 levels in male patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). A total of 84 eligible male patients (aged 30-60 years, HbA1c 7.0%-10.0%, CAP ≥248 dB/m, on stable metformin monotherapy for ≥8 weeks) will be randomized 1:1 to either continue metformin alone or receive metformin plus dapagliflozin 10 mg/day for 12 weeks. The primary endpoint is the change in serum IGF-1 from baseline to 3 months between groups. Secondary endpoints include changes in hepatic steatosis (CAP), liver stiffness (LSM), FIB-4 index, metabolic parameters, and safety outcomes. The study aims to determine whether adding dapagliflozin to metformin can restore the suppressed GH-IGF-1 axis and provide mechanistic insights into its hepatoprotective effects.

Conditions

Type 2 Diabetes; Metabolic Dysfunction-Associated Steatotic Liver Disease

Keywords

Dapagliflozin; Metformin; Serum IGF-1; Type 2 Diabetes Mellitus; Metabolic Dysfunction-Associated Steatotic Liver Disease

Outcome Measures

Primary Outcomes (2)

• ΔIGF-1

  The difference in the change value of serum IGF-1 levels (ΔIGF-1) from baseline to 3 months between the two groups.

  12 weeks

• Changes in non-invasive indicators of liver fibrosis

  Differences in the change values of the FIB-4 index from baseline to 3 months between the two groups

  12 weeks

Secondary Outcomes (8)

• Changes in liver fat content

  12 weeks

• Changes in non-invasive indicators of liver fibrosis

  12 weeks

• ΔIGF-1/IGFBP3 molar ratio

  12 weeks

• Changes in glucose metabolism indicators

  12 weeks

• ΔBMI

  12 weeks

Study Arms (2)

Metformin groups

ACTIVE COMPARATOR

Continue monotherapy with metformin (maintain the original dose).

Drug: Metformin

Metformin+ Dapagliflozin group

EXPERIMENTAL

Metformin (maintain the original dose) + Dapagliflozin 10 mg/day

Drug: Metformin + Dapagliflozin

Interventions

Metformin + Dapagliflozin DRUG

Maintain the stable pre-enrollment dose of metformin (≥1500 mg/day or maximum tolerated dose) plus dapagliflozin 10 mg/day orally, administered once daily before breakfast, for 3 consecutive months. Other concomitant medications (e.g., antihypertensives, lipid-lowering agents) for both groups should remain unchanged during the study period unless clinically necessary adjustments are required. Patients should be instructed to maintain stable dietary and exercise habits throughout the study.

Metformin+ Dapagliflozin group

Metformin DRUG

Maintain the stable pre-enrollment dose of metformin monotherapy (≥1500 mg/day or maximum tolerated dose) for 3 consecutive months. Other concomitant medications (e.g., antihypertensives, lipid-lowering agents) for both groups should remain unchanged during the study period unless clinically necessary adjustments are required. Patients should be instructed to maintain stable dietary and exercise habits throughout the study.

Metformin groups

Eligibility Criteria

• Age: 30 Years - 60 Years
• Gender Eligibility Details: There are significant differences in serum IGF-1 levels between males and females, along with distinct IGF-1 secretion patterns. IGF-1 secretion and metabolic disorders (e.g., fatty liver) are influenced by sex hormones (e.g., estrogen vs. testosterone) and genetic factors. For example: Estrogen may protect against fatty liver in females by reducing lipogenesis and inflammation6. Males often exhibit higher visceral fat accumulation and insulin resistance, increasing fatty liver risk. IGF-1 levels peak during puberty and decline with age, with males typically showing higher baseline levels than female.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males aged 30-60 years;
• Meeting the WHO diagnostic criteria for type 2 diabetes mellitus, with HbA1c levels between 7.0% and 10.0%;
• Having received a stable dose of metformin (≥1500 mg/day or the maximum tolerated dose) as monotherapy for at least 8 weeks;
• Meeting the diagnostic criteria for MASLD: Controlled Attenuation Parameter (CAP) value ≥248 dB/m detected, with the presence of at least one cardiometabolic risk factor;
• No prior use of SGLT2 inhibitors, insulin secretagogues, insulin, or GLP-1 receptor agonists;
• Willing to participate voluntarily and sign the informed consent form.

You may not qualify if:

• Type 1 diabetes mellitus or other specific types of diabetes;
• Weekly alcohol intake exceeding 210g for males;
• Concomitant chronic liver diseases (viral hepatitis, autoimmune liver disease, Wilson's disease, hemochromatosis, etc.);
• Known pituitary or hypothalamic diseases affecting the GH-IGF-1 axis;
• Previous or current use of GH preparations or IGF-1 preparations;
• Baseline estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73m²;
• Previous diagnosis of cardiovascular diseases (coronary heart disease, stroke, heart failure) or severe liver diseases (decompensated cirrhosis);
• Active malignant tumors;
• Allergy to dapagliflozin or similar drugs;
• Use of medications affecting IGF-1 levels (such as oral estrogens, high-dose glucocorticoids) within the past 3 months;
• Diabetic ketoacidosis, severe infection, or surgical stress within 1 month prior to enrollment.

Sponsors & Collaborators

• The 95th Hospital of Putian，Putian, Fujian, China: lead

Study Sites (1)

The Ethics Committee of Putian 95 Hospital

Putian, Fujian, 351100, China

Location

Related Publications (4)

• Srimanus K, Damrongmanee A, Ukarapol N, Chattipakorn N, Chattipakorn SC. Unveiling the link between insulin-like growth factor 1 (IGF-1) and fatty liver progression: From bench to bedside. Biochim Biophys Acta Mol Basis Dis. 2026 Jun;1872(5):168218. doi: 10.1016/j.bbadis.2026.168218. Epub 2026 Mar 6.

  PMID: 41796683 BACKGROUND

• Ma IL, Stanley TL. Growth hormone and nonalcoholic fatty liver disease. Immunometabolism (Cobham). 2023 Jul 27;5(3):e00030. doi: 10.1097/IN9.0000000000000030. eCollection 2023 Jul.

  PMID: 37520312 BACKGROUND

• Kineman RD, Del Rio-Moreno M, Waxman DJ. Liver-specific actions of GH and IGF1 that protect against MASLD. Nat Rev Endocrinol. 2025 Feb;21(2):105-117. doi: 10.1038/s41574-024-01037-0. Epub 2024 Sep 25.

  PMID: 39322791 RESULT

• Dichtel LE, Cordoba-Chacon J, Kineman RD. Growth Hormone and Insulin-Like Growth Factor 1 Regulation of Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab. 2022 Jun 16;107(7):1812-1824. doi: 10.1210/clinem/dgac088.

  PMID: 35172328 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Rongfeng Zhu

  The 95th Hospital of Putian

  STUDY CHAIR

Central Study Contacts

Rongfeng Zhu, Dr

CONTACT

+8613706058931; 123357213@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 21, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 10, 2027
• Study Completion (Estimated): December 11, 2027
• Last Updated: August 21, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)