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

Sponsor
Yangjin
Study ID
NCT05914857
Phase
PHASE2
Status
Unknown

Conditions

  • Impaired Fasting Glucose
  • Impaired Glucose Tolerance
  • Prediabetic State

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin 10mg Tab — DRUG
    Dapagliflozin Tablets, Oral, 10mg, Once daily
  • lifestyle interventions — BEHAVIORAL
    Consisting of 30 minutes of moderate-intensity exercise every day and a reduction of 300 calories in the total diet

Study Details

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.

Key Dates

Start date
Dec 20, 2023
Status verified
Jul 2023
Primary completion
Jun 1, 2025
Completion
Dec 1, 2025

Study Design

Enrollment
120 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Intervention group
    Patients in the intervention group will be administered Dapagliflozin 10 mg/day in addition to lifestyle intervention.
  • Placebo Comparator: Control group
    Patients in the control group will be given lifestyle intervention only.

Primary Outcome Measure

2h plasma glucose on an oral glucose tolerance test (OGTT) [ Time Frame: Change from baseline (time 0) to study end (12 weeks) ]

Central Contacts

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