Reversal to Normoglycemia by Treating Prediabetes

NCT07392151 | Not Yet Recruiting Phase 3

• 1 other identifier: 2025-522970-35-00
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

Prediabetes is a precursor to diabetes, but compared with diabetes, much less is known about prediabetes. Prediabetes is defined based on a blood sample measuring long-term average glucose levels. In the Danish population, about 7% have prediabetes, and roughly one in five will develop diabetes within five years. In the US, significantly more people have this condition - about 38% of the adult population - and it is reasonable to expect a growing global prevalence over the years. Diabetes is associated with various microvascular diseases, traditionally referred to as diabetic complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. However, it has been shown that some of these conditions are already present in some individuals with prediabetes, even though this condition does not meet the diagnostic criteria for diabetes. Several metabolic changes are often seen in people with prediabetes, including high cholesterol, hypertension, increased inflammatory markers, and obesity. Additionally, there is a possible link between prediabetes and the occurrence of fat accumulation in the liver. These risk factors are also believed to be associated with the development of coronary atherosclerosis. In individuals with coronary atherosclerosis there is an overrepresentation of prediabetes. Therefore, the investigators would like to investigate whether this group of people might benefit from having their long-term average glucose levels reduced to normal from prediabetes using glucose-lowering medication, which is approved for use in people with diabetes and has also shown a cardioprotective effect in individuals without diabetes. The medications that will be used for this purpose are: Semaglutide, administered once weekly as a subcutaneous injection. The dose will be gradually increased at 4-week intervals up to a maximum of 2.4 mg. If this is insufficient, it may be considered to start Dapagliflozin (Forxiga), 10 mg tablet daily. Both treatments are approved for use in Europe but are not currently used to treat prediabetes. A total of 108 individuals with prediabetes and coronary atherosclerosis who consent to participate in the trial will be randomly assigned (1:1) to two groups:

1. 1.Interventional therapy arm: Participants will attend visits at Aarhus University Hospital and begin glucose-lowering treatment. Additionally, any hypertension or high cholesterol will be optimized according to current guidelines. They will be offered lifestyle counselling. Participants will have their blood pressure measured regularly and, if necessary, blood samples are drawn to optimize the above.
2. 2.Conventional therapy arm: Participants will receive standard treatment either at the hospital or from their general practitioner, without any influence from the trial and without starting trial-related medication.

Conditions

Prediabetes; Chronic Coronary Syndrome

Keywords

Prediabetes; Chronic coronary syndrome; Coronary artery disease; Normoglycemia; Semaglutide; Dapagliflozin; Retinopathy; Neuropathy; Nephropathy; MASLD

Outcome Measures

Primary Outcomes (2)

• Presence of a composite of retinopathy, nephropathy, neuropathy, and MASLD

  Baseline

• Incidence of normoglycemia defined as HbA1c <39 mmol/mol

  1-year follow-up

Secondary Outcomes (33)

• Presence of: Retinopathy, Nephropathy, Neuropathy, or MASLD

  Baseline

• Presence of a composite of retinopathy, nephropathy, and neuropathy.

  Baseline

• Incidence of normoglycemia defined as HbA1c <42 mmol/mol

  1-year follow-up

• Change in HbA1c

  1-year follow-up

• Change in eGFR

  1-year follow-up

Study Arms (3)

Prediabetes: Interventional therapy arm

EXPERIMENTAL

Intensified medical follow-up and treatment including cardioprotective glucose-lowering drugs

Drug: Intensified medical follow-up and glucose-lowering drugs

Prediabetes: Conventional therapy arm

NO INTERVENTION

Current practice

Normoglycemia

OTHER

Baseline comparator group

Other: No intervention

Interventions

Intensified medical follow-up and glucose-lowering drugs DRUG

Intensified medical follow-up and treatment including cardioprotective glucose-lowering drugs

Prediabetes: Interventional therapy arm

No intervention OTHER

Baseline comparator group

Normoglycemia

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic coronary syndrome with documented coronary artery disease. In the case of previous myocardial infarction, at least 30 days between the event and randomization is required.
• Prediabetes defined as HbA1c 42-47 mmol/mol (IEC criteria) OR normoglycemia defined as HbA1c \<39 mmol/mol
• Age 18 to 80 years

You may not qualify if:

• eGFR \<30 mL/min/1.73 m2
• Previous diabetes diagnosis, previous HbA1c \>47 mmol/mol, or current/previous usage of diabetes medication
• Anemia, recent bleeding or blood transfusion (\<3 months)
• Previous pancreatitis
• Pregnancy, breastfeeding, or fertile women who do not use highly effective contraception
• Strongly reduced liver function
• Chronic alcohol abuse
• Known hemoglobinopathy and other conditions with effect on erythrocyte lifespan
• Intake of medications with known effect on HbA1c validity such as: antiretroviral medications, trimethoprim, sulfamethoxazole, sulfasalazine hydroxyurea, dapsone, acetylsalicylic acid (\>3 g/daily), high dose vitamin C and E.
• Heart failure with NYHA class III or IV Trial subjects must be capable of giving informed consent as assessed by the investigator.
• Patients with BMI\<25 kg/m2 will be assessed individually by an investigator for eligibility (e.g., whether initiation of a GLP-1 RA with potential weight loss is clinically justifiable).

Sponsors & Collaborators

• Aarhus University Hospital: collaborator
• Michael Mæng: lead
• GCP-unit at Aarhus University Hospital, Aarhus, Denmark: collaborator
• Department of Clinical Epidemiology, Aarhus University, DK-8200 Aarhus N, Denmark: collaborator
• University of Aarhus: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

MeSH Terms

Conditions

Prediabetic State; Coronary Artery Disease; Retinal Diseases; Kidney Diseases

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Eye Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Michael Maeng, MD, PhD

  Aarhus University Hospital, Department of Cardiology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pernille T Tonnesen, MD

CONTACT

+4551316945; pernille.tilma@clin.au.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Professor, FESC

Study Record Dates

• First Submitted: January 23, 2026
• First Posted: February 6, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: February 6, 2026

Record last verified: 2026-01

Locations

DK (1)