Type 2 Diabetes Mellitus (T2DM)NCT07713992
Efficacy and Safety of Mazdutide in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Nonalcoholic Fatty Liver Disease Previously Treated With Semaglutide
A study testing Mazdutide(Dual GLP-1R/GCGR Agonist) and Semaglutide (1 Mg Dose) in people with Type 2 Diabetes Mellitus (T2DM) and Nonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus, run by Tianjin Medical University.
Trial summary
This is a multicenter, prospective, randomized controlled investigator-initiated trial (IIT) aimed at evaluating the efficacy and safety of switching to mazdutide therapy in patients with type 2 diabetes mellitus (T2DM) and moderate-to-severe non-alcoholic fatty liver disease (NAFLD) who have achieved glycemic… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Type 2 Diabetes Mellitus (T2DM), Nonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus
- What is being tested?
- Mazdutide(Dual GLP-1R/GCGR Agonist) and Semaglutide (1 Mg Dose)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- 15 Sep 2026to 1 Feb 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged between 18 and 60 years (inclusive) at the time of informed consent signing.
- Diagnosed with type 2 diabetes mellitus.
- Received once-weekly semaglutide 1.0 mg treatment for at least 16 consecutive weeks verified by medication records.
- Diagnosed with moderate-to-severe fatty liver, defined as hepatic attenuation ≥269 dB/m by transient elastography and hepatic fat fraction >10% measured by MRI-PDFF.
- HbA1c level <7%.
- Body mass index (BMI) ≥24 kg/m².
- Glycemic and weight management regimens without adjustments within 3 months prior to screening.
- Voluntarily signed written informed consent and agreed to comply with the study protocol.
Who cannot join
- History of alcoholic fatty liver, drug-induced fatty liver, viral hepatitis, autoimmune diseases, or acute gallbladder diseases.
- Use of medications affecting fatty liver metabolism within 3 months prior to screening, including but not limited to SGLT-2 inhibitors, vitamin E, GLP-1R/GIPR agonists, liver-selective thyroid receptor β agonists, PPAR agonists, and aspirin.
- Use of weight-loss drugs or alternative weight-loss therapies within 3 months prior to screening.
- Addition to sulfonylureas, glinides, dorzagliatin, or various insulin preparations within 3 months prior to screening.
- History of bariatric surgery or planned bariatric surgery during the study (excluding acupuncture, liposuction and abdominal liposuction performed more than 1 year before screening).
- Diagnosed with type 1 diabetes or latent autoimmune diabetes in adults.
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- Personal history of acute or chronic pancreatitis, personal or family history of medullary thyroid carcinoma (MTC), or family history of multiple endocrine neoplasia type 2 (MEN2).
- Presence of severe cardiovascular, cerebrovascular, hepatic or renal insufficiency, uncontrolled diabetes, malignancy, cirrhosis or advanced liver fibrosis.
- Pregnant or lactating females, those planning pregnancy within half a year, or with recent major surgery or severe infection.
- Mental disorders or cognitive disorders that may interfere with study compliance, or any other conditions judged inappropriate for study participation by the investigator.
- Contraindications to MRI examination, including implantation of pacemakers, metallic heart valves, magnetic surgical clips, implantable electronic infusion pumps, severe claustrophobia, or inability to tolerate MRI scanning.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Efficacy and Safety of Mazdutide in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Nonalcoholic Fatty Liver Disease Previously Treated With Semaglutide: A Multicenter, Prospective, Randomized Controlled Trial (IIT)
This is a multicenter, prospective, randomized controlled investigator-initiated trial (IIT) aimed at evaluating the efficacy and safety of switching to mazdutide therapy in patients with type 2 diabetes mellitus (T2DM) and moderate-to-severe non-alcoholic fatty liver disease (NAFLD) who have achieved glycemic control.
Chinese patients with type 2 diabetes mellitus (T2DM) are susceptible to visceral fat accumulation, which increases the risk of cardiometabolic diseases and mortality. Metabolic associated fatty liver disease (MAFLD) is highly prevalent among Chinese T2DM patients, and the coexistence of T2DM and moderate-to-severe fatty liver significantly elevates liver-related and all-cause mortality. The vicious cycle of hepatic lipid deposition and insulin resistance aggravates T2DM progression, while weight loss has been proven to alleviate hepatopancreatic fat accumulation and improve the management of T2DM.
Read more
GLP-1 receptor agonists (GLP-1RAs) including semaglutide are standard therapies for T2DM with glycemic improvement and weight-loss benefits. However, nearly a quarter of patients show poor response to semaglutide. Long-term semaglutide treatment may cause GLP-1 receptor desensitization, and the agent lacks direct regulatory effects on adipose tissue and hepatic lipid metabolism. Clinically, many patients still have persistent moderate-to-severe fatty liver despite standardized semaglutide therapy, highlighting an unmet clinical need for optimized treatment.
Mazdutide is a novel dual GLP-1R/GCGR agonist. GCGR is highly expressed in the liver and adipose tissues. Via GCGR activation, mazdutide directly inhibits hepatic lipogenesis, promotes hepatic fat decomposition and fatty acid oxidation, and improves adipose tissue browning and thermogenesis. Compared with single GLP-1RAs, mazdutide exerts more direct and comprehensive regulatory effects on hepatic and systemic lipid metabolism, making it a promising option for T2DM patients with residual moderate-to-severe fatty liver after semaglutide treatment.
This study is a multicenter, prospective, stratified randomized controlled design and enrolls T2DM patients with persistent moderate-to-severe NAFLD after receiving subcutaneous semaglutide 1.0 mg once weekly for ≥28 weeks. with 1:1 group allocation and concealed grouping. Eligible subjects are randomized into two groups without drug washout: the intervention group switches to mazdutide therapy, while the control group continues semaglutide treatment. All baseline concomitant medications for metabolic diseases remain stable throughout the study to avoid confounding factors.
Mazdutide is titrated per official instructions, initiating at 2 mg once weekly and escalating to a 4 mg once weekly maintenance dose based on patient tolerability and efficacy. All participants maintain their habitual diet and exercise routines with regular lifestyle supervision to ensure study stability. After the initial intervention phase, patients with <30% reduction in hepatic fat content will receive a mazdutide dose increase to 6 mg once weekly. Meanwhile, the control group will cross over to mazdutide treatment, and all patients will enter the subsequent observational stage.
The primary endpoint is the change in hepatic fat content from baseline to study endpoint, measured by MRI-PDFF and liver elastography, to evaluate the efficacy of mazdutide on hepatic steatosis. Secondary endpoints include inter-group differences in glycemic control, body composition, islet function, liver enzymes and lipid profiles. The efficacy changes during the crossover period are also observed. All adverse events are recorded to assess the safety and tolerability of mazdutide in this patient population.
- Conditions
- Type 2 Diabetes Mellitus (T2DM), Nonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus
- Being tested
- Mazdutide(Dual GLP-1R/GCGR Agonist), Semaglutide (1 Mg Dose)
- Keywords
- Type 2 Diabetes Mellitus, Nonalcoholic Fatty Liver Disease, Mazdutide, Randomized Controlled Trial, Liver Fat Content
- Medical subject headings
- Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mazdutide(Dual GLP-1R/GCGR Agonist)Drug
Subcutaneous injection, once weekly for 16 weeks (first phase). Subjects switch from previous semaglutide 1.0 mg weekly to mazdutide 4 mg immediately, with no washout period.After 16-week initial treatment phase, subjects with <30% reduction in liver fat content from baseline will have mazdutide dose titrated up to 6 mg weekly as per study protocol.
Semaglutide (1 Mg Dose)Drug
Participants in the control group maintain the original treatment regimen of once-weekly subcutaneous semaglutide 1.0 mg throughout the trial without dose adjustment or drug switching. No washout period is implemented prior to randomization. Concomitant hypoglycemic, antihypertensive and lipid-lowering medications remain unchanged as baseline. Subjects will only cross over to mazdutide after completion of the initial intervention phase.
| Study group | Role | What they receive |
|---|---|---|
| Mazdutide Treatment Group | Experimental | Subjects in this arm immediately discontinue subcutaneous semaglutide 1.0 mg once weekly, and switch to subcutaneous mazdutide therapy in accordance with the study protocol. After the initial intervention period, subjects with an intrahepatic fat content reduction rate ≥ 30% continue the original mazdutide dose; subjects with an intrahepatic fat content reduction rate < 30% are titrated to mazdutide 6 mg. Administration route, frequency and standard initial dose follow the approved drug label and study protocol. Receives: Drug: Mazdutide(Dual GLP-1R/GCGR Agonist) |
| Semaglutide Maintenance Group | Active comparator | Subjects in this arm continue maintenance treatment with subcutaneous semaglutide 1.0 mg once weekly, consistent with their pre-study treatment regimen. After the initial intervention period, all subjects in this arm cross over to receive mazdutide therapy and enter the extended follow-up phase. No dose adjustment of semaglutide is allowed during the control treatment period. Receives: Drug: Semaglutide (1 Mg Dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute change in liver fat content measured by MRI-PDFF
Measured: Baseline, Week 16, Week 32
Absolute change in liver fat content measured by liver transient elastography
Measured: Baseline, Week 16, Week 32
Secondary outcomes (14)
Absolute change in fasting plasma glucose (FPG)
Measured: Baseline, Week 16, Week 32
Absolute change in glycated hemoglobin (HbA1c)
Measured: Baseline, Week 16, Week 32
Changes in derived indices from oral glucose tolerance test (OGTT) from baseline to study endpoint
Measured: Baseline, Week 16, Week 32
Absolute change in liver stiffness measurement (LSM)
Measured: Baseline, Week 16, Week 32
Absolute change in body weight
Measured: Baseline, Week 16, Week 32
Absolute change in total cholesterol (TC)
Measured: Baseline, Week 16, Week 32
Number of Grade 2 clinically significant hypoglycemic episodes
Measured: Baseline through Week 32
Absolute change in fibrosis-4 index (FIB-4)
Measured: Baseline, Week 16, Week 32
Number of adverse events
Measured: Baseline through Week 32
Absolute change in body mass index (BMI)
Measured: Baseline, Week 16, Week 32
Absolute change in triglycerides (TG)
Measured: Baseline, Week 16, Week 32
Absolute change in high-density lipoprotein cholesterol (HDL-C)
Measured: Baseline, Week 16, Week 32
Number of Grade 3 severe hypoglycemic episodes
Measured: Baseline through Week 32
Number of allergic reaction events
Measured: Baseline through Week 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2026
- Study start15 Sep 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes Mellitus (T2DM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Tianjin TEDA Hospital, Tianjin First Central Hospital, Tianjin Third Central Hospital, Tianjin Fifth Central Hospital
- Responsible party
- Principal investigator, Zhenqiang Song, Tianjin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07713992
- Sponsor's protocol ID
- ●JXYJNYYkMEC2026-32
- Status last verified
- Jul 2026
- First submitted
- 9 Jul 2026
- Last updated
- 20 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sanchez-Garrido MA, Brandt SJ, Clemmensen C, Muller TD, DiMarchi RD, Tschop MH. GLP-1/glucagon receptor co-agonism for treatment of obesity. Diabetologia. 2017 Oct;60(10):1851-1861. doi: 10.1007/s00125-017-4354-8. Epub 2017 Jul 21.
PubMed 28733905Del Prato S, Gallwitz B, Holst JJ, Meier JJ. The incretin/glucagon system as a target for pharmacotherapy of obesity. Obes Rev. 2022 Feb;23(2):e13372. doi: 10.1111/obr.13372. Epub 2021 Oct 28.
PubMed 34713962Habegger KM, Heppner KM, Geary N, Bartness TJ, DiMarchi R, Tschop MH. The metabolic actions of glucagon revisited. Nat Rev Endocrinol. 2010 Dec;6(12):689-97. doi: 10.1038/nrendo.2010.187. Epub 2010 Oct 19.
PubMed 20957001Al-Massadi O, Ferno J, Dieguez C, Nogueiras R, Quinones M. Glucagon Control on Food Intake and Energy Balance. Int J Mol Sci. 2019 Aug 11;20(16):3905. doi: 10.3390/ijms20163905.
PubMed 31405212van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond). 2014 Jun;38(6):784-93. doi: 10.1038/ijo.2013.162. Epub 2013 Sep 3.
PubMed 23999198Targher G, Valenti L, Byrne CD. Metabolic Dysfunction-Associated Steatotic Liver Disease. N Engl J Med. 2025 Aug 14;393(7):683-698. doi: 10.1056/NEJMra2412865. No abstract available.
PubMed 40802944Nauck MA, Quast DR, Wefers J, Pfeiffer AFH. The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update. Diabetes Obes Metab. 2021 Sep;23 Suppl 3:5-29. doi: 10.1111/dom.14496.
PubMed 34310013Jones B. The therapeutic potential of GLP-1 receptor biased agonism. Br J Pharmacol. 2022 Feb;179(4):492-510. doi: 10.1111/bph.15497. Epub 2021 May 20.
PubMed 33880754Gasoyan H, Butsch WS, Schulte R, Casacchia NJ, Le P, Boyer CB, Griebeler ML, Burguera B, Rothberg MB. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obesity (Silver Spring). 2025 Sep;33(9):1657-1667. doi: 10.1002/oby.24331. Epub 2025 Jun 10.
PubMed 40491239Jiao R, Lin C, Cai X, Wang J, Wang Y, Lv F, Yang W, Ji L. Characterizing body composition modifying effects of a glucagon-like peptide 1 receptor-based agonist: A meta-analysis. Diabetes Obes Metab. 2025 Jan;27(1):259-267. doi: 10.1111/dom.16012. Epub 2024 Oct 21.
PubMed 39431379Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5.
PubMed 29221645Taylor R. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia. 2008 Oct;51(10):1781-9. doi: 10.1007/s00125-008-1116-7. Epub 2008 Aug 26.
PubMed 18726585Yi W, Kim K, Im M, Ryang S, Kim EH, Kim M, Jeon YK, Kim SS, Kim BH, Pak K, Kim IJ, Kim SJ. Association between visceral adipose tissue volume, measured using computed tomography, and cardio-metabolic risk factors. Sci Rep. 2022 Jan 10;12(1):387. doi: 10.1038/s41598-021-04402-5.
PubMed 35013484Reijrink M, de Boer SA, Spoor DS, Lefrandt JD, Lambers Heerspink HJ, Boellaard R, Greuter MJ, Borra RJH, Hillebrands JL, Slart RHJA, Mulder DJ. Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors. Atherosclerosis. 2019 Nov;290:87-93. doi: 10.1016/j.atherosclerosis.2019.09.016. Epub 2019 Sep 25.
PubMed 31604171Jia W, Chan JC, Wong TY, Fisher EB. Diabetes in China: epidemiology, pathophysiology and multi-omics. Nat Metab. 2025 Jan;7(1):16-34. doi: 10.1038/s42255-024-01190-w. Epub 2025 Jan 14.
PubMed 39809974
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Mazdutide in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Nonalcoholic Fatty Liver Disease Previously Treated With Semaglutide: A Multicenter, Prospective, Randomized Controlled Trial (IIT)
- ClinicalTrials.gov ID
- NCT07713992
- Acronym / sponsor ID
- ●JXYJNYYkMEC2026-32
- Conditions
- Type 2 Diabetes Mellitus (T2DM), Nonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus
- Keywords
- Type 2 Diabetes Mellitus, Nonalcoholic Fatty Liver Disease, Mazdutide, Randomized Controlled Trial, Liver Fat Content
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Tianjin Medical UniversityUniversity, hospital or other
- Collaborators
- Tianjin TEDA Hospital, Tianjin First Central Hospital, Tianjin Third Central Hospital, Tianjin Fifth Central Hospital
- Study start
- 15 Sep 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 1 Feb 2028 (estimated)
- First posted
- 20 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, prospective, randomized controlled investigator-initiated trial (IIT) aimed at evaluating the efficacy and safety of switching to mazdutide therapy in patients with type 2 diabetes mellitus (T2DM) and moderate-to-severe non-alcoholic fatty liver disease (NAFLD) who have achieved glycemic control.
Chinese patients with type 2 diabetes mellitus (T2DM) are susceptible to visceral fat accumulation, which increases the risk of cardiometabolic diseases and mortality. Metabolic associated fatty liver disease (MAFLD) is highly prevalent among Chinese T2DM patients, and the coexistence of T2DM and moderate-to-severe fatty liver significantly elevates liver-related and all-cause mortality. The vicious cycle of hepatic lipid deposition and insulin resistance aggravates T2DM progression, while weight loss has been proven to alleviate hepatopancreatic fat accumulation and improve the management of T2DM.
GLP-1 receptor agonists (GLP-1RAs) including semaglutide are standard therapies for T2DM with glycemic improvement and weight-loss benefits. However, nearly a quarter of patients show poor response to semaglutide. Long-term semaglutide treatment may cause GLP-1 receptor desensitization, and the agent lacks direct regulatory effects on adipose tissue and hepatic lipid metabolism. Clinically, many patients still have persistent moderate-to-severe fatty liver despite standardized semaglutide therapy, highlighting an unmet clinical need for optimized treatment.
Mazdutide is a novel dual GLP-1R/GCGR agonist. GCGR is highly expressed in the liver and adipose tissues. Via GCGR activation, mazdutide directly inhibits hepatic lipogenesis, promotes hepatic fat decomposition and fatty acid oxidation, and improves adipose tissue browning and thermogenesis. Compared with single GLP-1RAs, mazdutide exerts more direct and comprehensive regulatory effects on hepatic and systemic lipid metabolism, making it a promising option for T2DM patients with residual moderate-to-severe fatty liver after semaglutide treatment.
This study is a multicenter, prospective, stratified randomized controlled design and enrolls T2DM patients with persistent moderate-to-severe NAFLD after receiving subcutaneous semaglutide 1.0 mg once weekly for ≥28 weeks. with 1:1 group allocation and concealed grouping. Eligible subjects are randomized into two groups without drug washout: the intervention group switches to mazdutide therapy, while the control group continues semaglutide treatment. All baseline concomitant medications for metabolic diseases remain stable throughout the study to avoid confounding factors.
Mazdutide is titrated per official instructions, initiating at 2 mg once weekly and escalating to a 4 mg once weekly maintenance dose based on patient tolerability and efficacy. All participants maintain their habitual diet and exercise routines with regular lifestyle supervision to ensure study stability. After the initial intervention phase, patients with <30% reduction in hepatic fat content will receive a mazdutide dose increase to 6 mg once weekly. Meanwhile, the control group will cross over to mazdutide treatment, and all patients will enter the subsequent observational stage.
The primary endpoint is the change in hepatic fat content from baseline to study endpoint, measured by MRI-PDFF and liver elastography, to evaluate the efficacy of mazdutide on hepatic steatosis. Secondary endpoints include inter-group differences in glycemic control, body composition, islet function, liver enzymes and lipid profiles. The efficacy changes during the crossover period are also observed. All adverse events are recorded to assess the safety and tolerability of mazdutide in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mazdutide Treatment Group | Experimental | Drug: Mazdutide(Dual GLP-1R/GCGR Agonist)Subjects in this arm immediately discontinue subcutaneous semaglutide 1.0 mg once weekly, and switch to subcutaneous mazdutide therapy in accordance with the study protocol. After the initial intervention period, subjects with an intrahepatic fat content reduction rate ≥ 30% continue the original mazdutide dose; subjects with an intrahepatic fat content reduction rate < 30% are titrated to mazdutide 6 mg. Administration route, frequency and standard initial dose follow the approved drug label and study protocol. |
| Semaglutide Maintenance Group | Active comparator | Drug: Semaglutide (1 Mg Dose)Subjects in this arm continue maintenance treatment with subcutaneous semaglutide 1.0 mg once weekly, consistent with their pre-study treatment regimen. After the initial intervention period, all subjects in this arm cross over to receive mazdutide therapy and enter the extended follow-up phase. No dose adjustment of semaglutide is allowed during the control treatment period. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Aged between 18 and 60 years (inclusive) at the time of informed consent signing.
- Diagnosed with type 2 diabetes mellitus.
- Received once-weekly semaglutide 1.0 mg treatment for at least 16 consecutive weeks verified by medication records.
- Diagnosed with moderate-to-severe fatty liver, defined as hepatic attenuation ≥269 dB/m by transient elastography and hepatic fat fraction >10% measured by MRI-PDFF.
- HbA1c level <7%.
Key exclusion criteria (11 listed)
- History of alcoholic fatty liver, drug-induced fatty liver, viral hepatitis, autoimmune diseases, or acute gallbladder diseases.
- Use of medications affecting fatty liver metabolism within 3 months prior to screening, including but not limited to SGLT-2 inhibitors, vitamin E, GLP-1R/GIPR agonists, liver-selective thyroid receptor β agonists, PPAR agonists, and aspirin.
- Use of weight-loss drugs or alternative weight-loss therapies within 3 months prior to screening.
- Addition to sulfonylureas, glinides, dorzagliatin, or various insulin preparations within 3 months prior to screening.
- History of bariatric surgery or planned bariatric surgery during the study (excluding acupuncture, liposuction and abdominal liposuction performed more than 1 year before screening).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mazdutide(Dual GLP-1R/GCGR Agonist)Subcutaneous injection, once weekly for 16 weeks (first phase). Subjects switch from previous semaglutide 1.0 mg weekly to mazdutide 4 mg immediately, with no washout period.After 16-week initial treatment phase, subjects with <30% reduction in liver fat content from baseline will have mazdutide dose titrated up to 6 mg weekly as per study protocol. | Drug | Mazdutide Treatment Group |
| Semaglutide (1 Mg Dose)Participants in the control group maintain the original treatment regimen of once-weekly subcutaneous semaglutide 1.0 mg throughout the trial without dose adjustment or drug switching. No washout period is implemented prior to randomization. Concomitant hypoglycemic, antihypertensive and lipid-lowering medications remain unchanged as baseline. Subjects will only cross over to mazdutide after completion of the initial intervention phase. | Drug | Semaglutide Maintenance Group |
Primary outcome
Absolute change in liver fat content measured by MRI-PDFF
Time frame: Baseline, Week 16, Week 32
Absolute change in liver fat content measured by liver transient elastography
Time frame: Baseline, Week 16, Week 32
14 secondary outcomes
Absolute change in fasting plasma glucose (FPG)
Time frame: Baseline, Week 16, Week 32
Absolute change in glycated hemoglobin (HbA1c)
Time frame: Baseline, Week 16, Week 32
Changes in derived indices from oral glucose tolerance test (OGTT) from baseline to study endpoint
Time frame: Baseline, Week 16, Week 32
Absolute change in liver stiffness measurement (LSM)
Time frame: Baseline, Week 16, Week 32
Absolute change in body weight
Time frame: Baseline, Week 16, Week 32
Absolute change in total cholesterol (TC)
Time frame: Baseline, Week 16, Week 32
Number of Grade 2 clinically significant hypoglycemic episodes
Time frame: Baseline through Week 32
Absolute change in fibrosis-4 index (FIB-4)
Time frame: Baseline, Week 16, Week 32
Number of adverse events
Time frame: Baseline through Week 32
Absolute change in body mass index (BMI)
Time frame: Baseline, Week 16, Week 32
Absolute change in triglycerides (TG)
Time frame: Baseline, Week 16, Week 32
Absolute change in high-density lipoprotein cholesterol (HDL-C)
Time frame: Baseline, Week 16, Week 32
Number of Grade 3 severe hypoglycemic episodes
Time frame: Baseline through Week 32
Number of allergic reaction events
Time frame: Baseline through Week 32
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- Background: PubMed 28733905Sanchez-Garrido MA, Brandt SJ, Clemmensen C, Muller TD, DiMarchi RD, Tschop MH. GLP-1/glucagon receptor co-agonism for treatment of obesity. Diabetologia. 2017 Oct;60(10):1851-1861. doi: 10.1007/s00125-017-4354-8. Epub 2017 Jul 21.
- Background: PubMed 34713962Del Prato S, Gallwitz B, Holst JJ, Meier JJ. The incretin/glucagon system as a target for pharmacotherapy of obesity. Obes Rev. 2022 Feb;23(2):e13372. doi: 10.1111/obr.13372. Epub 2021 Oct 28.
- Background: PubMed 20957001Habegger KM, Heppner KM, Geary N, Bartness TJ, DiMarchi R, Tschop MH. The metabolic actions of glucagon revisited. Nat Rev Endocrinol. 2010 Dec;6(12):689-97. doi: 10.1038/nrendo.2010.187. Epub 2010 Oct 19.
- Background: PubMed 31405212Al-Massadi O, Ferno J, Dieguez C, Nogueiras R, Quinones M. Glucagon Control on Food Intake and Energy Balance. Int J Mol Sci. 2019 Aug 11;20(16):3905. doi: 10.3390/ijms20163905.
- Background: PubMed 23999198van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond). 2014 Jun;38(6):784-93. doi: 10.1038/ijo.2013.162. Epub 2013 Sep 3.
- Background: PubMed 40802944Targher G, Valenti L, Byrne CD. Metabolic Dysfunction-Associated Steatotic Liver Disease. N Engl J Med. 2025 Aug 14;393(7):683-698. doi: 10.1056/NEJMra2412865. No abstract available.
- Background: PubMed 34310013Nauck MA, Quast DR, Wefers J, Pfeiffer AFH. The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update. Diabetes Obes Metab. 2021 Sep;23 Suppl 3:5-29. doi: 10.1111/dom.14496.
- Background: PubMed 33880754Jones B. The therapeutic potential of GLP-1 receptor biased agonism. Br J Pharmacol. 2022 Feb;179(4):492-510. doi: 10.1111/bph.15497. Epub 2021 May 20.
- Background: PubMed 40491239Gasoyan H, Butsch WS, Schulte R, Casacchia NJ, Le P, Boyer CB, Griebeler ML, Burguera B, Rothberg MB. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obesity (Silver Spring). 2025 Sep;33(9):1657-1667. doi: 10.1002/oby.24331. Epub 2025 Jun 10.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing Mazdutide(Dual GLP-1R/GCGR Agonist) and Semaglutide (1 Mg Dose) in people with Type 2 Diabetes Mellitus (T2DM) and Nonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus, run by Tianjin Medical University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zsong (86-22-18602276218, Zsong@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute change in liver fat content measured by MRI-PDFF (time frame: Baseline, Week 16, Week 32). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07713992, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.