Podcast Summary: Preventing Type 1 Diabetes? Dr. Michael Haller on ATG Research (Plus, Afrezza for Kids)

Diabetes Connections | Type 1 Diabetes
Host: Stacey Simms
Guest: Dr. Michael Haller, Professor and Chief of Pediatric Endocrinology, University of Florida
Date: December 2, 2025

Overview

In this rich, information-packed episode, Stacey Simms sits down with Dr. Michael Haller—a leading pediatric endocrinologist—to discuss cutting-edge research on two of the most anticipated subjects in the Type 1 diabetes community:

• The promise of low-dose ATG (antithymocyte globulin) for preventing or delaying Type 1 diabetes
• The state of Afrezza (inhaled insulin) for kids and its journey through FDA approval

Dr. Haller provides both clinical insight and personal perspective, making this episode essential listening for anyone tracking advances in Type 1 diabetes prevention, treatment, and the potential for altering the disease’s course.

Key Topics & Discussion Points

1. Dr. Haller’s Background and the Exciting Era in Type 1 Research

• Timestamp: [05:20]
• Dr. Haller is a professor and chief of pediatric endocrinology at the University of Florida, leading clinical trials and advocacy in the Type 1 diabetes research space.
• Noted the field is witnessing major momentum: advances in prevention, new pumps, CGMs, and the emergence of inhaled insulin for kids.

2. Low-dose ATG (Antithymocyte Globulin): What Is It and How Does It Work?

• Timestamp: [06:44]

• What is ATG?

  • Long-used in transplantation to suppress/adjust the immune system.
  • The research team explored if a low dose could be immunomodulating (not fully suppressing), providing a “Goldilocks” therapeutic effect for new-onset Type 1 diabetes with remaining beta cell function.

• Key Early Trials:

  • Pilot trial: Low dose ATG plus GCSF showed preservation of beta cell function, leading to a larger, multicenter TrialNet study.
  • In TrialNet, low-dose ATG alone outperformed ATG+GCSF and placebo, preserving C-peptide (marker of beta cell function) and reducing A1C for two years after only a two-day infusion.

• Patient Success:

  • Amber Vandenhoovel, trial participant, retained beta cell function five years post-infusion.

  "Low dose ATG actually by itself...provided a highly significant preservation of C peptide out to two years after a simple two day infusion of this drug and reduced hemoglobin A1C compared to placebo."
  — Dr. Haller [08:25]

3. Type 1 Diabetes Staging and the Push Towards Prevention

• Timestamp: [10:12]
• Stages explained:
  • Stage 1: Multiple antibodies, no symptoms, long preclinical phase.
  • Stage 2: Positive antibodies and abnormal glucose metabolism but not yet insulin-dependent.
  • Stage 3: Clinical onset of diabetes (classic symptoms, insulin dependency).
• ATG trials have evolved to target Stage 2—possibly preventing/delaying full onset—and new trials are being planned.

4. ATG Dose Optimization—The "Therapeutic Window"

• Timestamp: [12:12]

• Three-arm trial demonstrated ATG alone is most effective; GCSF has been dropped from future protocols.

• The MEld-ATG study (Europe):

  • "Minimally Effective Low Dose" as low as 0.5 mg/kg also preserved beta cell function.
  • Ongoing research to personalize which dose is optimal.

  "Now we need to figure out which doses work best for which patients and which situations...we're moving into this era of hopefully personalized immunotherapy."
  — Dr. Haller [13:50]

5. ATG vs. Tzield (Teplizumab): Key Differences and Comparative Trials

• Timestamp: [14:28]

• Tzield (teplizumab): The first FDA-approved immunotherapy to delay Type 1 onset—works via different mechanism (anti-CD3 monoclonal antibody).

• Contrast with ATG:

  • ATG: Older, cheaper, two-day outpatient infusion (as opposed to Tzield’s 14-day regimen and ~$194,000 cost).
  • Both work to modulate the immune attack, but through different targets and protocols.

• Studies are transitioning to head-to-head comparative effectiveness trials (no more placebo arms), enrolling children as young as 4.

  "Low dose ATG...has some significant advantages. But we have to, you know, first do the studies to see if it works as well as teplizumab...That's a good thing. Our space is going to absolutely need more than one...induction agent."
  — Dr. Haller [18:10]

6. The Path to Trial Participation & The Importance of Screening

• Timestamp: [20:01]

• TrialNet: The premier pathway for screening and eligibility for prevention trials.

• Any first- or second-degree relatives of people with Type 1 should get screened—fast, free, via mailed kits or clinics.

• Clinical guidelines now recommend antibody screening even outside research.

  "My big PSA for today is if you have a family member with type 1 diabetes...please get them screened."
  — Dr. Haller [20:01]

7. The Future of Immunotherapy: Will We Ever "Cure" or Permanently Prevent?

• Timestamp: [22:33]

• The field aspires for true prevention—perpetually delaying, or completely stopping, Type 1 onset.

• Most likely path: repeated induction/maintenance therapy (as is done in rheumatology, allergy, cancer).

• The last decade’s progress: moving from symptom management (insulin) to addressing root autoimmunity.

  "It's a bit naive to assume that we can give a drug once and walk away...We're just at the end of the beginning of immunotherapies."
  — Dr. Haller [24:12]

8. Science-Fiction Made Real: Fully Human ATG from "Humanized" Cows

• Timestamp: [24:59]

• Traditional ATG made with rabbit serum—some patients develop serum sickness.

• SAB Bio now produces fully human ATG by immunizing genetically engineered cows (so-called “humanized” cows).

• This eliminates serum sickness risk and could enable repeated treatments.

  "You can now immunize these cows...and the cows see those thymocytes as being foreign and they make antibodies...fully human...eliminates that serum sickness."
  — Dr. Haller [25:32]

9. Inhaled Insulin (Afrezza) for Kids: Rapid-Action, Study Results, and What’s Next

• Timestamp: [27:14]

• Afrezza advantages: True “ultra-rapid” action—peaks in 5–10 mins, gone by 45 mins (vs. hours for subcutaneous insulins).

• INHALE-1 Study (published in Diabetes Care): Non-inferior to injected insulin in kids/adolescents; no major safety issues.

  • Some patients excel with inhaled, others do better on injections—personalization is key.
  • Most effective as adjunct (e.g., for pizza, stubborn highs, or with automated insulin delivery).

  "It's the fastest insulin we have available...can help patients achieve better control, especially in specific situations—around hard meals or sports or activity or correcting, you know, right before bed."
  — Dr. Haller [35:50]

• Approval for pediatrics anticipated in 2026; future studies planned on using Afrezza at diagnosis and with hybrid closed-loop systems.

• Safety: In pediatric studies (and adults), no negative pulmonary function signals; those with primary lung disease are not candidates.

10. Notable Quotes & Inspiring Moments

• On the acceleration of progress:

  "The pace, the acceleration that we're seeing, does make me excited for the future...I think we will eventually get there."
  — Dr. Haller [36:53]

• On his personal connection:

  "My grandfather had type 1 diabetes. Even though I'm now bald and getting old myself, I'm not so old that I don't remember...when we didn't have glucose meters...to think how far the field has come."
  — Dr. Haller [36:53]

• On what keeps him motivated:

  "Hopefully improving the lives of kids and adults living with Type one, hopefully meaningfully preventing disease and hopefully one day reversing it."
  — Dr. Haller [37:20]

Time-Stamped Highlights

• [05:20] Introduction of Dr. Haller and the current state of T1D research
• [06:44] What is ATG, and how did the initial prevention trials work?
• [08:25] Major findings from the early and later ATG studies
• [10:12] Understanding the new stages of Type 1 diabetes and screening
• [12:12] Dose optimization and the move towards personalized immunotherapy
• [14:28] Comparison: ATG vs. Tzield (Teplizumab)—mechanism, access, cost, logistics
• [18:10] Study design evolution—no more placebo, comparative effectiveness
• [20:01] TrialNet screening and ‘why’ everyone at risk should do it
• [22:33] The (realistic) future: repeated/maintenance therapy for lasting diabetes prevention
• [24:59] Humanized cows and new, more tolerable forms of ATG on the horizon
• [27:14] Afrezza in children—what did the pediatric trials show?
• [35:50] Afrezza’s advantages, safety profile, and practical use-cases in pediatrics
• [36:53] Dr. Haller’s passion, personal family history, and continued hope for the field
• [39:06] Diabetes organizations that shaped Dr. Haller’s career

Resources & Organizations Cited

[36:53; 39:06] Dr. Haller’s recommended organizations for support, research, and advocacy:

• Breakthrough T1D (formerly JDRF)
• TrialNet
• Helmsley Charitable Trust
• American Diabetes Association (ADA)
• International Society for Pediatric and Adolescent Diabetes (ISPAD)

Closing Thoughts

Dr. Haller gives a hopeful, realistic, and deeply informed overview of where T1D prevention research stands—offering practical advice for families and an inspiring sense of progress. Both low-dose ATG and inhaled insulin represent real, actionable advances, and participation in screening and research is vital to accelerating discoveries.

Memorable Closing Quote:

"We're just at the sort of end of the beginning of immunotherapies...hopefully the next hundred years will see us convert [type 1 diabetes] to something we identify before anybody ever needs insulin and then can kick the can down the road indefinitely by way of safe and effective therapies."
— Dr. Haller [24:12]

For more information:

• TrialNet clinical studies and screening: trialnet.org
• Detailed notes and resources linked in the episode show notes

Summary prepared for listeners seeking actionable insights and the state of the art in T1D prevention and treatment.