ADA Updates Standards of Care to Include Teplizumab for Delaying T1D, Reflect Emphasis on NAFLD

Robert Gabbay, MD, PhD
Credit: LinkedIn

The American Diabetes Association (ADA) has released updates to the organization’s Standards of Care in Diabetes—2023 to provide the community with guidance around a pair of topics: Teplizumab for Type 1 Diabetes and Nonalcoholic Fatty Liver Disease (NAFLD).

Announced on June 25, 2023, the updates, which were debuted during the 83rd Scientific Sessions of the ADA (ADA 2023), endorse the use of teplizumab (Tzield) for delaying the onset of type 1 diabetes and also emphasize the importance of early detection of NAFLD in people with diabetes as well as appropriate management modalities.^1,2

“ADA is committed to preventing and curing diabetes, a complex, chronic illness that requires continuous medical care. For more than 30 years, ADA has been actively involved in the development of clinical practice recommendations that clinicians, researchers, health plans, policymakers, and others can rely on to guide diabetes care,” said Robert Gabbay, chief scientific and medical officer at the ADA.²

Teplizumab for Delaying Onset of Type 1 Diabetes

The approval of teplizumab in November 2022 was a landmark moment for the diabetes community. The first agent to receive approval from the US Food and Drug Administration for delaying the onset of type 1 diabetes, but, even during the celebration of this achievement, many in the community knew they faced an uphill battle.

As with any novel agent, pertains to educating clinicians and patients on the drug itself becomes a focal point, but, for teplizumab, the hurdles to optimal use are multifaceted because of a lack of awareness around screening and staging of type 1 diabetes. In fact, one of the most significant changes to the Standards of Care, as it pertains to teplizumab, is the title of the section itself, with the writing committee dropping the term Type 2 from the section title to read: Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2023.³

The approval of teplizumab was based on data from the TN10 trial. A randomized double-blind, placebo-controlled clinical trial, TN10 enrolled 76 patients and randomized them in a 1:1 ratio to teplizumab or placebo therapy. Upon analysis, results of the trial suggested the median time to diagnosis in the intervention arm was 48.4 months compared to 24.4 months in placebo arm. In a median of 2 years of follow-up, type 1 diabetes was diagnosed in 43% of teplizumab arm and 72% of placebo arm (HR, 0.41; 95% CI, 0.22-0.78; P = .006). Extended follow-up data from this trial suggests the median time to clinical type 1 diabetes diagnosis was 59.6 months with teplizumab arm and 27.1 months in the placebo arm. In a median of 2.5 years of follow-up, type 1 diabetes was diagnosed in 50% of the teplizumab arm and 78% of the placebo arm (HR, 0.457; P= .01).⁴

Before section 2 concludes, the final paragraph outlines the importance of screening programs and their availability in the US as well as the potential detrimental effect of delayed screening and identification of type 1 diabetes autoantibodies.³

The specific updates to recommendations in sections 2 and 3 are as follows:

Recommendation 2.5: Screening for presymptomatic type 1 diabetes may be done by detection of autoantibodies to insulin, glutamic acid decarboxylase (GAD), islet antigen 2, or zinc transporter 8. B³

Recommendation 2.6: Multiple confirmed islet autoantibodies is a risk factor for clinical diabetes. Testing for dysglycemia may be used to further forecast near-term risk. When multiple islet autoantibodies are identified, referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes should be considered. B³

Recommendation 3.14 Teplizumab-mzwv infusion to delay the onset of symptomatic type 1 diabetes should be considered in selected individuals aged ≥8 years with stage 2 type 1 diabetes. Management should be in a specialized setting with appropriately trained personnel. B⁵

"Type 1 diabetes is a devastating disease that affects millions of people worldwide, and there is a great need for effective treatments," said Nuha El Sayed, MD, MM Sc, chair of the Professional Practice Committee and overseer of ADA’s Standards of Care in Diabetes.¹

Renewed Emphasis on Nonalcoholic Fatty Liver Disease

With NAFLD present in up to 70% of people with type 2 diabetes, but no FDA-approved treatments, NAFLD poses a significant challenge for endocrinologists, hepatologists, and primary care. Although treatments are not specifically indicated for treatment of NAFLD, studies have suggested some therapies such as GLP-1 receptor agonists could provide benefit in some patients with type 2 diabetes and NAFLD.

As part of the updates released during the ADA 2023 meeting, recommendation 4.10 has been replaced by new recommendations 4.11a, 4.11b, 4.12, and 4.13. In addition to replacing prior recommendations, the standards also feature 9 additional recommendations following recommendation 4.13. Some of these new recommendations are highlighted below:⁶

Recommendation 4.14 Adults with type 2 diabetes or prediabetes particularly with overweight or obesity with nonalcoholic fatty liver disease should be recommended lifestyle changes that promote weight loss, ideally within a structured nutrition plan and physical activity program for cardiometabolic benefits B and histological improvement. C⁶

Recommendation 4.15 For adults with type 2 diabetes particularly with overweight or obesity with nonalcoholic fatty liver disease, consider using a glucagon-like peptide 1 receptor agonist with demonstrated benefits in nonalcoholic steatohepatitis as an adjunctive therapy to lifestyle interventions for weight loss. B⁶

Recommendation 4.19a Consider metabolic surgery in appropriate candidates as an option to treat nonalcoholic steatohepatitis in adults with type 2 diabetes and nonalcoholic steatohepatitis B and improve cardiovascular outcomes. B⁶

Recommendation 4.19b Metabolic surgery should be used with caution in adults with type 2 diabetes with compensated cirrhosis from nonalcoholic fatty liver disease B and is not recommended in decompensated cirrhosis. B⁶

“Diabetes and liver disease are closely linked, and it is essential that healthcare professionals have the most current information to effectively detect and manage this disease,” ElSayed said.²

1. American Diabetes Association releases updates to the 2023 standards of care in diabetes on the use of teplizumab in delaying the onset of type 1 diabetes. American Diabetes Association Releases Updates to the 2023 Standards of Care in Diabetes on the Use of Teplizumab in Delaying the Onset of Type 1 Diabetes | ADA. June 25, 2023. Accessed June 25, 2023. https://diabetes.org/newsroom/press-releases/2023/american-diabetes-association-releases-updates-2023-standards-of-care-diabetes-use-teplizumab-delaying-onset-type-1-diabetes.
2. American Diabetes Association releases a guideline update in NAFLD (non-alcoholic fatty liver disease) and diabetes. American Diabetes Association Releases a Guideline Update in NAFLD (Non-Alcoholic Fatty Liver Disease) and Diabetes | ADA. June 25, 2023. Accessed June 25, 2023. https://diabetes.org/newsroom/press-releases/2023/american-diabetes-association-releases-guideline-update-NAFLD-diabetes.
3. ElSayed NA, Aleppo G, Aroda VR, et al. Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S19–S40. Diabetes Care 2023; dc23ad08. https://doi.org/10.2337/dc23-ad08
4. Campbell P. Teplizumab receives FDA approval for delaying type 1 diabetes. HCP Live. https://www.hcplive.com/view/teplizumab-receives-fda-approval-for-delaying-type-1-diabetes. Published November 20, 2022. Accessed June 25, 2023.
5. ElSayed NA, Aleppo G, Aroda VR, et al. Addendum. 3. Prevention or Delay of Type 2 Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S41–S48. Diabetes Care 2023; dc23ad08a. https://doi.org/10.2337/dc23-ad08a
6. ElSayed NA, Aleppo G, Aroda VR, et al. Addendum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S49–S67. Diabetes Care 2023; dc23ad09. https://doi.org/10.2337/dc23-ad09