EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES OFFICIAL HIGHLIGHTS

EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES

Conference summaries


PREVENTION

Results from the Anti-CD3 mAb (teplizumab) prevention trial

Presented by: Kevan Herold, MD
Department of Internal Medicine, Yale University, New Haven, CT, USA Peter S. Linsley, PhD
Systems Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA
  • Immune interventions such as the anti-CD3 monoclonal antibody teplizumab are considered promising in delaying decline in beta-cell function.
  • A single two-week course of treatment with teplizumab delayed progression to clinical type 1 diabetes in relatives of patients with type 1 diabetes who were at high-risk for development of disease by a median of 2 years.
  • This is the first trial to demonstrate that immune therapy can delay the onset of type 1 diabetes.

Several immune interventions in patients with recent-onset clinical type 1 diabetes have been reported to delay the decline in beta-cell function. Fc receptor–nonbinding anti-CD3 monoclonal antibodies, such as teplizumab, appear to show promise, and studies in patients with type 1 diabetes have suggested that teplizumab reduces loss of beta-cell function, although it is unclear if interventions at stage 1 or 2 can alter progression to clinical type 1 diabetes.

  • Assess whether treatment with teplizumab treatment can prevent or delay the onset of clinical type 1 diabetes in persons at high-risk.

Type of study, patients, and inclusion criteria

  • Phase 2, randomised, placebo-controlled, double-blind trial.
  • Eligible participants were nondiabetic relatives of patients with type 1 diabetes and at least 8 years of age at the time of randomisation and at high risk for development of clinical diabetes.
  • Participants had to have had two or more diabetes-related autoantibodies detected in two samples obtained within 6 months before randomisation.
  • Participants had to have had evidence of dysglycaemia by oral glucose-tolerance test (fasting glucose 110-125 mg/dL), 2-hour postprandial plasma glucose 140-200 mg/dL, or an intervening postprandial glucose level at 30, 60, or 90 minutes >200 mg/dL on two occasions, within 52 days before enrolment.

Patient population

  • Total patients randomised: 76.
  • Patients were randomly assigned to a single 14-day course of teplizumab or placebo.
  • Teplizumab (n = 44).
  • Placebo (n = 32).

Primary outcome measure

  • Elapsed time from randomisation to clinical diagnosis of type 1 diabetes with American Diabetes Association criteria.
  • Median time to diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group.
  • Type 1 diabetes was diagnosed in 19 (43%) of participants who received teplizumab and in 23 (72%) of those who received placebo.
  • The hazard ratio for diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% CI, 0.22-0.78; P = 0.006).
  • Annualised rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group.
  • As expected, rash and transient lymphopenia were observed.
  • TIGIT+KLRG1+ CD8+ T cells were more common with teplizumab vs placebo.
  • Among participants who were HLA-DR3–negative, HLA-DR4–positive, or anti–zinc transporter 8 antibody–negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed.
  • A single two-week course of treatment with teplizumab delayed progression to clinical diabetes in high-risk relatives of patients with type 1 diabetes.
  • Some subgroups of patients have particularly robust responses to teplizumab.

Key Messages/Clinical Perspectives

  • This is the first trial to show that immune therapy can be used to delay the onset of type 1 diabetes.
  • This has particular significance for children.

 

Trial: NCT01030861



References

References


  1. Herold KC, Bundy BN, Long SA, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. Circulation 2019 Aug 27;140(9):739-50

Presenter disclosure: The presenters has reported the follow relationships: K. Herold: Toleron and Tiziana Pharma, BMS, Lilly, Merck, Semma, Forkhead, GSK, Roche, ProventionBio.  P.S. Linsley: BMS.

Medical writer: Patrick Moore, PhD

Reviewer: Marco Gallo, MD

Local reviewers: Marco Gallo, MD (Italia); Anna Novials Sardá, MD, PhD (España); Eric Renard, MD, PhD (France); Peter Schwarz, MD, PhD (Deutschland) 

Scientific Editor: Florian Toti, MD


CLINICAL TRIALS

T2D & NEPHROPATY

CREDENCE – Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Presented by: Carol Pollock, MBBS, PhD, FRACP, AAHMS; Hiddo Lambers Heerspink, PharmD, PhD; Kenneth W. Mahaffey, MD

PREVENTION

Results from the Anti-CD3 mAb (teplizumab) prevention trial

Presented by: Kevan Herold, MD; Peter S. Linsley, PhD

DIABETES & CVD

DECLARE study: call for action

Presented by: Itamar Raz, MD; Ofri Mosenzon, MD, MSc; Avivit Cahn, MD

T2D TREATMENT

VERIFY – Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes

Presented by: Chantal Mathieu, MD; Michael Stumvoli, MD; David R. Matthews, MD; Stefano del Prato, MD

DIABETES & HF

DAPA-HF: dapagliflozin and prevention of adverse-outcomes in heart failure

Presented by: Mikhail Kosiborod, MD; Silvio Inzucchi, MD

CV SAFETY

Results and implications of CAROLINA (CARdiOvascular Safety of LINAgliptin) comparing linagliptin vs glimepiride

Presented by: Julio Rosenstock, MD; Mark A. Espeland, MD; Steven E. Kahn, MD; Nikolaus Marx, MD; Bernard Zinman, MD; Darren McGuire, MD

T2D & CV PREVENTION

T1D DETERMINANTS

The Environmental Determinants of Diabetes in the Young (TEDDY) study

Presented by: Anette-Gabriele Ziegler, MD; Heikki Hyöty, MD, PhD
 

SYMPOSIA

NAFLD & DIABETES

EASD/EASL Symposium: is NAFLD a risk for health in the context of diabetes?

Presented by: Michael Roden, MD; Stefano Romeo, MD; Elisabetta Bugianesi, MD, PhD

HF & T2D

EASD/ESC Symposium: heart failure in type 2 diabetes

Presented by: M. Louis Handoko, MD; Javed Butler, MD, MPH, MBA

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