SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes

Summary

More than 50% of patients with type 2 diabetes develop micro- and/or macrovascular complications during the course of the disease. Additionally, many patients at risk for diabetes develop metabolically driven complications including kidney and heart disease. Thus, it is of utmost importance to improve prevention of T2D and with this complications. Remission of prediabetes, i.e. normalization of hyperglycemia by means of lifestyle intervention is one of the most effective ways to prevent the development of T2D and complications. Novel sub-phenotyping analysis identified clusters of risk for diabetes associated with different complications, opening opportunities to new therapeutic approaches, despite and in addition to lifestyle changes. So far, pharmacological therapy is not indicated for patients with prediabetes. Remission of hyperglycemia associated with prediabetes during lifestyle interventions not only prevents T2D but is also linked with reduced albuminuria and lower microvascular and kidney complications. Thus, reaching normoglycemia (i.e. prediabetes remission) is important for reducing the risk of (pre-)diabetes-associated complications including micro- and even macrovascular disease. In patients with T2D, recent data show that dapagliflozin can improve diabetes remission, and thus, likely complications. However, to date no data have assessed whether or not this is also true in patients with hyperglycemia related to prediabetes which, as outlined above, already causes different complications.

Subphenotyping of patients with newly onset diabetes suggests that for some individuals, it would be too late to start interventions against dagainst complications at the time of diagnosis of type 2 diabetes. Therefore, individuals at elevated risk to develop T2D and complications should receive preventive measures well before the diagnosis of T2D. This study will provide evidence whether such an early intervention contributes to the remission of hyperglycemia related to prediabetes to protect from associated complications such as renal disease. The studied population will comprise individuals who have hyperglycemia in the range of prediabetes and are thus prone to not only develop T2D, but also early nephropathy but in clinical practice do not receive medical treatment due to the early stage of the disease. These subjects will receive Dapagliflozin 10 mg or Placebo for 6 months. The placebo treatment arm reflects current practice. In order guarantee a benefit the patients in the placebo arm will receive a lifestyle intervention.

Conditions

• Type2diabetes
• PreDiabetes
• Renal Failure

Interventions

DRUG

Dapagliflozin (Forxiga®)

Dapagliflozin 10 mg once daily for 6 months. Route of administration: oral.

DRUG

Placebo matching Dapaglifolzin

Placebo matching Dapaglifolzin once daily for 6 months. Route of administration: oral.

BEHAVIORAL

Lifestyle Intervention

Patients receive a conventional lifestyle intervention (one in depth individual session at the beginning and standard care information on a healthy lifestyle at every visit thereafter).

Sponsors & Collaborators

• German Federal Ministry of Education and Research

  collaborator OTHER_GOV

• German Center for Diabetes Research

  collaborator OTHER

• AstraZeneca

  collaborator INDUSTRY

• University Hospital Tuebingen

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

35 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-10-26

Primary Completion

2027-06-30

Completion

2027-09-30

Countries

• Germany

Study Locations