Evaluation of the Safety and Efficacy of SGLT2 Inhibitors in Pre-diabetic Patients

NCT05914857 | Unknown Phase 2

• 1 other identifier: 80497
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Pre-diabetes is a state characterized by subclinical impairment in glycemic variables that is intermediate between normal glucose tolerance (NGT) and diabetes. There are two frequently used definitions for pre-diabetes, one from the American Diabetes Association (ADA) and another from the World Health Organization (WHO), and both include impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and a calibrated hemoglobin A1c (HbA1c) of between 5.7 and 6.4%. More than 30 % of the global population demonstrated one or more forms of prediabetic dysglycaemia. In general, approximately 70 % of individuals with IFG and/or IGT can expect to go on to develop clinical type 2 diabetes at some time in the future, and the risk increases with higher HbA1c levels and with higher BMI. Worse still, the prevalence of pre-diabetes is increasing worldwide, with a growing number of patients progressing to diabetes. Identification and treatment of pre-diabetic individuals is therefore crucial. Recent evidence suggested that preventing progression of pre-diabetes to diabetes is possible, and thus efficacious interventions for pre-diabetic individuals are the cornerstone of diabetes prevention. The current paradigm for diabetes prevention in high-risk individuals focuses on achieving moderate weight loss via dietary change and increasing physical activity. However, lifestyle-based weight-loss strategies may initially be successful, but difficult to achieve or maintain. In many cases, pharmacologic treatments may be needed to regulate blood glucose. Randomized clinical trials (RCTs) have verified the efficacy of metformin in preventing insulin resistance syndrome, along with the progression of microvascular diseases and heart attacks. Meanwhile, clinical experience and trial data have yielded almost no significant safety concerns for metformin. Nonetheless, it may cause discomfort for up to 25% of patients who experience diarrhea and nausea subsequent to its administration. For patients with a contraindication or intolerable adverse effects to metformin, Sodium Glucose Cotransporter 2 (SGLT-2) inhibitors with novel mode of action may be another alternative. Large clinical trials have not yet identified a substantial elevation in the frequency of adverse reactions related to SGLT-2 inhibitors when compared to the placebo group. Inhibition of SGLT-2 has some extra advantages for diabetes management over other therapeutic approaches. Firstly, the SGLT-2 is exclusively expressed in renal proximal tubules, and thus selective inhibitors will exert a glucose-lowering effect, independently of insulin secretion. Therefore, SGLT-2 inhibitors can cause weight loss without inducing major hypoglycemic events. Secondly, the cardiovascular benefits of SGLT-2 inhibitors was supported by large clinical trials in the modern context of antiplatelet, statin, and blood pressure management, which may match many of the advantages of metformin. Thirdly, SGLT-2 inhibitors have also been proven to prevent nephropathy for its restriction on albuminuria and inflammatory processes, and to subsequently dampen the deterioration in renal function. Overall, SGLT-2 inhibitors have demonstrated safety in non-diabetic patients, particularly in those afflicted with heart or kidney failure, and have shown to provide additional benefits. At present, the overall effectiveness and safety of SGLT-2 inhibitors in improving metabolism of pre-diabetic patients are still unclear. The purpose of this experiment is to evaluate the effect of SGLT-2 inhibitor on pre-diabetic patients.

Conditions

Prediabetic State; Impaired Fasting Glucose; Impaired Glucose Tolerance

Keywords

Prediabetic State; Impaired Fasting Glucose; Impaired Glucose Tolerance; Sodium-glucose co-transporter 2 inhibitor; Dapagaliflozin

Outcome Measures

Primary Outcomes (1)

• 2h plasma glucose on an oral glucose tolerance test (OGTT)

  2h-PG change

  Change from baseline (time 0) to study end (12 weeks)

Secondary Outcomes (8)

• Change in HbA1c

  Change from baseline (time 0) to study end (12 weeks)

• Change in Body Weight

  Change from baseline (time 0) to study end (12 weeks)

• Change in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

  Change from baseline (time 0) to study end (12 weeks)

• Change in Waist Circumference (WC)

  Change from baseline (time 0) to study end (12 weeks)

• Glycemic control including Fasting Blood Glucose (FBG) and Glycosylated Hemoglobin (HbA1C)

  Change from baseline (time 0) to study end (12 weeks)

Study Arms (2)

Intervention group

EXPERIMENTAL

Patients in the intervention group will be administered Dapagliflozin 10 mg/day in addition to lifestyle intervention.

Drug: Dapagliflozin 10mg Tab; Behavioral: lifestyle interventions

Control group

PLACEBO COMPARATOR

Patients in the control group will be given lifestyle intervention only.

Behavioral: lifestyle interventions

Interventions

Dapagliflozin 10mg Tab DRUG

Dapagliflozin Tablets, Oral, 10mg, Once daily

Also known as: Dapagliflozin Tablets

Intervention group

lifestyle interventions BEHAVIORAL

Consisting of 30 minutes of moderate-intensity exercise every day and a reduction of 300 calories in the total diet

Control group; Intervention group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 \~65 years old;
• OGTT received within half a year and were diagnosed with prediabetes In accordance with the gout classification criteria of the American Diabetes Association: ① Fasting blood glucose (FPG)≥6.1 mmol/L and \< 7.0 mmol/L; ② The blood glucose (2h-PG) concentration at OGTT 2h was ≥7.8 and \< 11.1mmol/L; ③ Glycosylated hemoglobin (HbA1c) ≥5.7% and \< 6.4%;
• No antidiabetic drugs (including traditional Chinese medicine) were taken within 6 months before screening;
• Sign the informed consent form.

You may not qualify if:

• Diagnosed with diabetes;
• Taking medications that affect glucose and lipid metabolism (excluding thiazide diuretics at a daily dose of ≤ 12.5 mg);
• Taking weight-loss drugs (including traditional Chinese medicine) within 6 months before screening;
• Patients with acute infection, surgery, acute alcoholism, mental illness, etc;
• Patients with liver and kidney dysfunction, severe chronic gastrointestinal disease, uncontrolled thyroid disease, cancer, and ventilator use;
• Systolic blood pressure ≥180 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure ≥110 mmHg at screening;
• Electrocardiogram within 12 weeks before screening indicating arrhythmia requiring urgent diagnosis or treatment (e.g., clinically newly identified severe arrhythmia or conduction disturbance), myocardial infarction, unstable angina, or stroke requiring cardiovascular and cerebrovascular intervention;
• A history of traumatic amputation within the past year, or active skin ulcers, osteomyelitis, gangrene, or critical lower limb ischemia within the past 6 months;
• Enrolled in drug/device clinical studies (including vaccines) within 12 weeks before screening;
• Pregnant, lactating women, or those planning a recent pregnancy;
• Allergic constitution or multi-drug allergy;
• Receiving bariatric surgery within the past 2 years.

Sponsors & Collaborators

• Yangjin: lead
• Peking University Third Hospital: collaborator

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Related Publications (1)

• Zhu X, Xia L, Yin D, Yang J, Wei R. Evaluating the Safety and Efficacy of Sodium-Glucose Co-transporter 2 Inhibitors in Subjects with Prediabetes: A Protocol for a Randomized Controlled Trial. Diabetes Ther. 2024 May;15(5):1231-1244. doi: 10.1007/s13300-024-01560-3. Epub 2024 Mar 18.

  PMID: 38494571 DERIVED

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Study Officials

• Jin Yang, doctorate

  Peking University Third Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Yang, Associate chief physician

CONTACT

82122515; yangjin@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate chief physician

Study Record Dates

• First Submitted: May 6, 2023
• First Posted: June 22, 2023
• Study Start: December 20, 2023
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)