Efficacy of Henagliflozin for Weight Loss in Obesity Without Diabetes

Efficacy of Henagliflozin for Weight Loss in Obesity Without Diabetes: a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

This trial is conducted in China. The purpose of the 24-week trial is to investigate the efficacy of henagliflozin to induce body weight loss and the purpose of the extension is to evaluate the hypoglycemic effect of henagliflozin in obese subjects without diabetes.

Trial has the following two periods: 1) A 12-week randomized, double-blind, placebo-controlled, multi-center trial for evaluating the efficacy of henagliflozin to induce body weight loss; 2) A 12-week multicenter randomized controlled open-label trial for evaluating the hypoglycemic effect of henagliflozin followed by a 24-week extension period.

Study Overview

• Status: Not yet recruiting
• Conditions: Weight Loss; Obese; Pre-diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Henagliflozin

Detailed Description

Primary Hypothesis:

The 12-week henagliflozin taking could induce significantly higher weight loss in obese subjects without diabetes, compared to diet-exercise therapy.

Assessment time points:

Baseline: prior to taking henagliflozin or diet-exercise therapy V1: 4 weeks following the henagliflozin taking or diet-exercise therapy V2: 4 weeks following V1 V3: 4 weeks following V2

Specific Aims 1:

To examine and compare the weight loss, assessed by weight, waist circumference, hip circumference and BMI, after 12-week henagliflozin taking or diet-exercise therapy in obese without diabetes.

Specific Aims 2:

To examine and compare the change of glucose level after 12-week henagliflozin taking or diet-exercise therapy in obese without diabetes.

Secondary Hypothesis 1:

The 24-week henagliflozin taking could siginificantly improve the glucose control in obese subjects with pre-diabetes, compared to diet-exercise therapy.

Assessment time points:

Baseline: prior to taking henagliflozin or diet-exercise therapy V4: 12 weeks following V3

Specific Aims:

To examine and compare the change of glucose level, assessed by fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin levels, after 24-week henagliflozin taking or diet-exercise therapy.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fei Hua, PHD; Phone Number: +86-0519-68876242; Email: huafei1970@suda.edu.cn
• Study Contact Backup: Name: Xiaolin Huang, PHD; Phone Number: +86-0519-68876242; Email: hxl4038@czfph.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years old≤age≤65 years old, regardless of gender and race
2. Nondiabetic population: without hypoglycemic treatment, FPG<7.0 mmol/l, PPG<11.1 mmol/l, and HbA1c<6.5%
3. obesity: BMI≥28 kg/m2
4. Stable weight: weight change less than 5kg in the past 3 months
5. Ability to understand and sign the informed consent form

Exclusion Criteria:

1. Allergies to Henagliflozin or its formulations;
2. Participants have been definitely diagnosed with diabetes;
3. HbA1c≥6.5 % or FPG≥7.0 mmol/l, or PPG≥11.1 mmol/l;
4. Participants have used glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose linked transporter-2 (SGLT-2) inhibitors, or other weight loss related drugs within the past 3 months;
5. History of bariatric surgery;
6. Untreated or uncontrolled hypothyroidism/hyperthyroidism;
7. High risk of urinary tract infection;
8. Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome);
9. Diagnosis of congenital glucose-galactose malabsorption or familial renal glycosuria
10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 times the upper limit of the normal range (UNL); Total bilirubin (TBIL) ≥ 2.0 times the upper limit of the normal range;
11. estimated glomerular filtration rate (eGFR)<30 mL/min/1.73 m2 or end-stage kidney disease, or requiring dialysis;
12. History of major depressive disorder or other severe psychiatric disorders, e.g. schizophrenia, bipolar disorder within the last 2 years;
13. Uncontrolled treated/untreated hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg)
14. myocardial infarction, unstable angina, revascularization surgery, or cerebrovascular diseases within the past 3 months;
15. Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer) or other severe diseases, which in the investigator's opinion could interfere with the results of the trial;
16. Females of child-bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) within 24 months;
17. Participation in a clinical trial within the last 3 months prior to screening;
18. Previous history of gestational diabetes;
19. Previous history of eating disorders;
20. Current or history of treatment with medications that may cause significant weight gain, within 3 months prior to screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium);
21. Diet attempts using herbal supplements or over-the-counter medications within 3 months before screening
22. Any lifetime history of a suicidal attempt or a history of any suicidal behavior in the last month prior to randomization;
23. Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the investigator
24. Known or suspected abuse of alcohol or narcotics
25. Subjects from the same house hold participating in the trial
26. Other situations which were inappropriate to the trial, at the discretion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Placebo and diet-exercise therapy	Drug: Placebo; Placebo and diet-exercise therapy; Other Names: diet-exercise therapy
Experimental: Intervention group; 10mg of Henagliflozin and diet-exercise therapy	Drug: Henagliflozin; 10mg of Henagliflozin and diet-exercise therapy; Other Names: diet-exercise therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight change	Proportion of weight change from baseline	3 months (12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of ≥5% weight loss	Proportion of patients who lost at least 5% of their body weight from baseline	3 months (12 weeks)
Incident diabetes	New-onset diabetes during follow up	1 month (4 weeks), 2 months (8 weeks), 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute weight change	Absolute value of weight change from baseline for each group at the 3rd month	3 months (12 weeks)
BMI change	Change in BMI from baseline for each group at the 3rd month. BMI was defined as weight (kg) divided by height squared (m2), weight and height will be combined to report BMI in kg/m^2.	3 months (12 weeks)
Change of waist circumference	Change of waist circumference at the 3rd month	3 months (12 weeks)
Change of waist-to-hip ratio	Change of waist-to-hip ratio at the 3rd month. Waist-to-hip ratio will be defined as waist circumference (cm) to hip circumference (cm).	3 months (12 weeks)
Change of FPG	Change of FPG from baseline	3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Change of PPG	Change of PPG from baseline	3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Changes of insulin levels	Changes of fasting and oral glucose tolerance test-2h insulin level from baseline	3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks)
Changes of C-peptide levels	Changes of fasting and oral glucose tolerance test-2h C-peptide levels from baseline	3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks)
Changes of HbA1c	Changes of HbA1c levels from baseline	3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Changes of triglyceride	Changes in triglyceride from baseline	6 months (24 weeks), 12 months (48 weeks)
Changes of total cholesterol	Changes in total cholesterol from baseline	6 months (24 weeks), 12 months (48 weeks)
Changes of LDL-c	Changes in LDL-c from baseline	6 months (24 weeks), 12 months (48 weeks)
Changes of HDL-c	Changes in HDL-c from baseline	6 months (24 weeks), 12 months (48 weeks)
Change of urinary albumin-to-creatinine ratio	Change of urinary albumin-to-creatinine ratio from baseline in each group	6 months (24 weeks), 12 months (48 weeks)
Changes of C-reactive protein	Changes of C-reactive protein in each group relative to baseline	6 months (24 weeks), 12 months (48 weeks)

Collaborators and Investigators

• Sponsor: The First People's Hospital of Changzhou
• Collaborators: The First Affiliated Hospital of Soochow University; Second Affiliated Hospital of Soochow University; Affiliated Hospital of Jiangsu University; The Affiliated Hospital of Xuzhou Medical University; The First People's Hospital of Lianyungang; Wuxi People's Hospital; The Second Hospital of Nanjing Medical University; Northern Jiangsu People's Hospital; The fourth affiliated hospital of nantong university
• Investigators: Principal Investigator: Ling Yang, MD, Affiliated Hospital of Jiangsu University; Principal Investigator: Yu Liu, PHD, Sir Run Run Hospital, Nanjing Medical University; Principal Investigator: Bimin Shi, PHD, First Affiliated Hospital of Soochow University; Principal Investigator: Ji Hu, Second Affiliated Hospital of Soochow University; Principal Investigator: Xiaowei Zhu, PHD, Wuxi People's Hospital; Principal Investigator: Zhenwen Zhang, PHD, Northern Jiangsu People's Hospital; Principal Investigator: Hongwei Ling, MD, The Affiliated Hospital of Xuzhou Medical University; Principal Investigator: Ning Xu, Bachelor, The First People's Hospital of Lianyungang; Principal Investigator: Yanmei Liu, MD, Yancheng No.1 People's Hospital

Publications and helpful links

General Publications

• Wang Y, Zhao L, Gao L, Pan A, Xue H. Health policy and public health implications of obesity in China. Lancet Diabetes Endocrinol. 2021 Jul;9(7):446-461. doi: 10.1016/S2213-8587(21)00118-2. Epub 2021 Jun 4.
• WHO Guidelines on Physical Activity and Sedentary Behaviour. Geneva: World Health Organization; 2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK566045/
• Wang Y, Mi J, Shan XY, Wang QJ, Ge KY. Is China facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in China. Int J Obes (Lond). 2007 Jan;31(1):177-88. doi: 10.1038/sj.ijo.0803354. Epub 2006 May 2.
• Wang Y, Xue H, Sun M, Zhu X, Zhao L, Yang Y. Prevention and control of obesity in China. Lancet Glob Health. 2019 Sep;7(9):e1166-e1167. doi: 10.1016/S2214-109X(19)30276-1. No abstract available.
• Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITYEXECUTIVE SUMMARYComplete Guidelines available at https://www.aace.com/publications/guidelines. Endocr Pract. 2016 Jul;22(7):842-84. doi: 10.4158/EP161356.ESGL.
• American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S17-S38. doi: 10.2337/dc22-S002.

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Obese; Weight loss; Glucose; Henagliflozin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight Changes; Diabetes Mellitus; Weight Loss; Prediabetic State; Body Weight
• Other Study ID Numbers: 2023-science-150

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data in the current study arisen from a dataset of Department of Endocrine and Metabolic Diseases, the First People's Hospital of Changzhou, Third Affiliated Hospital of Soochow University, are not publicly available due to security consideration, but are available from the corresponding author on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No