Diabetes Core Update – March 2026

American Diabetes Association Podcast
Release Date: February 27, 2026
Hosts: Dr. Neal Skolnick & Dr. John J. Russell

Episode Overview

This March 2026 episode of Diabetes Core Update delivers concise, clinically relevant reviews of five recent key articles in diabetes research and practice. The hosts—Dr. Neal Skolnick and Dr. John J. Russell—discuss innovations and implications ranging from AI in screening, advances in GLP-1 medication, FDA regulatory changes, statin safety, and vision risks connected to modern therapies. Each segment analyzes the new data with a focus on real-world applicability for clinicians.

Key Discussion Points & Insights

1. AI in Diabetic Retinopathy Detection

Article: “Real World Prospective Validation and Economic Evaluation of Deep Learning-Based Diabetic Retinopathy Detection from Fundus Photographs: A Systematic Review and Meta-analysis” (Diabetes Care)

• Summary:
  • Reviewed the feasibility and economic impact of AI (deep learning)-based screening for diabetic retinopathy using fundus photographs in diverse global settings.
  • Meta-analysis pooled 47 studies; AI performed exceptionally well in detecting vision-threatening diabetic retinopathy (AUC 0.974) and any retinopathy (AUC 0.959), with cost-effectiveness in high- and some middle-income countries.
• Clinical Takeaways:
  • AI-aided fundus photography can extend access to screening, especially for patients not seeing eye doctors regularly.
  • Real-world application may be best in resource-rich settings; quality assurance and ophthalmologist oversight remain vital.
  • The shift enables ophthalmologists to focus on live or surgical cases rather than screening images.

“The pooled performance was highest in detecting vision-threatening diabetic retinopathy. The area under the receiver operating curve was 0.974... Above 0.9 is considered really good.” — Dr. Neal Skolnick [03:49]

“This is infinitely better for our patients who do not find their way to the eye doctors... I think this is an exciting thing and we are going to see more of this happening, especially for things that are static.” — Dr. John J. Russell [04:08–06:07]

2. Oral GLP-1 Agonist Orforglipron in Type 2 Diabetes & Obesity (ATTAIN-2 Trial)

Article: “Orforglipron, an Oral Small Molecule GLP-1 Receptor Agonist for the Treatment of Obesity in Type 2 Diabetes: The ATTAIN 2 Trial” (Lancet)

• Study Design:
  • 72-week, phase 3, double-blind, placebo-controlled trial across 10 countries (n = 2,800+), BMI ≥27, A1c 7–10%.
  • Randomized to 6mg, 12mg, 36mg orforglipron or placebo; all received lifestyle support.

• Key Results:
  • Mean percentage body weight change at 72 weeks:

  • 6mg: -5.1%
  • 12mg: -7.0%
  • 36mg: -9.6%
  • Placebo: -2.5%
    • All weight and cardiometabolic measures (A1C, waist, BP, lipids) improved with orforglipron.
    • Greater adverse events, mostly GI-related; higher discontinuations during escalation.

• Clinical Implications:
  • Orforglipron is a highly absorbable (70–80%) oral, non-peptide GLP-1, unlike oral semaglutide (~2–3% absorption).
  • No food/water restrictions, easier to transport and store worldwide (non-cold chain). • Anticipated as an accessible alternative to injectables, with significant impact for both diabetes and obesity management.

“This will, if it gets FDA approved... be an excellent option for people with obesity and for people with diabetes and obesity.” — Dr. Neal Skolnick [11:12]

3. FDA Removal of Suicidal Ideation Warning for GLP-1 Agonists

• Background:
  • The FDA reviewed all available clinical and real-world data, finding no increased risk of suicidal ideation or behavior with GLP-1 agonists used for obesity or diabetes.

• Evidence Reviewed:
  • Meta-analysis of 91 placebo-controlled trials (100,000+ patients)—no increased risk found.
  • Administrative claims study (2 million+ patients)—again, no increased risk of intentional self-harm.
  • Consistency across subgroups and observational studies.

• Significance:
  • All evidence supports removing the warning from GLP-1 labels for obesity treatment; reflects ongoing post-marketing vigilance and ensures labeling reflects up-to-date science.

• Broader Context:
  • Label warnings often assigned preemptively; removal only after robust, long-term safety review.
  • Highlights importance of large-scale post-marketing surveillance to detect rare adverse events—essential for medication safety.

“After that comprehensive review, the recommendation to withdraw this warning.” — Dr. Neal Skolnick [16:50]

“If something happens 1 in 10,000 patients, you’re not going to see it in a study that had 3,000 people in the treatment arm. So... post-marketing information is what allows us to be as safe as we can.” — Dr. John J. Russell [19:54]

4. Statins’ Effectiveness & Safety in Type 2 Diabetes by Cardiovascular Risk

Article: “Effectiveness and Safety of Statins in Type 2 Diabetes According to Baseline Cardiovascular Risk: A Target Trial Emulation Study” (Annals of Internal Medicine)

• Study Details:
  • Observational, target trial emulation of >25,000 UK patients (age 25–84) with type 2 diabetes, 2005–2016, without baseline CVD.
  • New statin initiators propensity-matched to non-initiators; stratified by 10-year predicted CV risk: low (<10%), intermediate, high, very high (>30%).

• Findings:
  • Statin initiation reduced all-cause and major CV mortality across all risk strata—absolute risk reduction even in low-risk (~0.5% over 10 years).
  • Small increase in myopathy only in moderate-risk stratum; no liver dysfunction risk elevating.

• Context & Caution:
  • ADA guidelines recommend moderate-intensity statins for all adults ≥40 with diabetes.
  • Target trial emulation tries to mimic randomized control but is still observational—potential for confounding persists (e.g., healthier patients/doctors more likely to prescribe statins).

“I don’t disagree with the conclusion that statins are likely beneficial for people at less than the usual 7.5% ASCVD risk or 10 year risk. But... target trial emulation studies... might have confounding variables.” — Dr. Neal Skolnick [25:04]

5. GLP-1 Agonists and Vision/Optic Nerve Risks

Article: “GLP-1 Receptor Agonists and the Risk of Optic Nerve or Vision-Threatening Events in Patients with Type 2 Diabetes or Cardiometabolic Disease: Meta-analysis of RCTs” (Diabetes Care)

• Scope:
  • Meta-analysis of 20 RCTs (n > 83,000, mean follow-up ~3 years).
  • Primary endpoint: composite of optic nerve or vision-threatening serious adverse events.

• Results:
  • No statistically significant increased risk for vision events (e.g., ischemic optic neuritis, papilledema, ischemic syndrome, blindness, blurred vision, reduced acuity).
  • Odds ratios consistently not significant even for those with preexisting retinopathy.

• Clinical Relevance:
  • Reassuring for clinicians—no evidence that GLP-1s cause vision-threatening events at a detectable rate.
  • Events so rare (e.g., ~1 in 10,000) that even large studies may not detect extremely uncommon risks; ongoing vigilance remains important.

“They found that no one was at increased risk of anything that lost their vision... better glycemic control... is going to lead long term to better retinal health.” — Dr. John J. Russell [30:36]

Notable Quotes & Memorable Moments

• On AI in Retinopathy Screening:

  “Deep learning was something I used to think you and I did, but now it refers to AI...” — Dr. Neal Skolnick [00:29]

• On the promise of oral GLP-1 therapies:

  “Absorption orally is in the rate of 70 to 80%. That's fantastic. Very different than oral semaglutide where the absorption is only about 2 to 3%.” — Dr. Neal Skolnick [11:12]

• On safety signal evolution:

  “It's well—how come they didn't know? Well, if something happens 1 in 10,000 patients, you're not going to see it in a study that had 3,000 people in the treatment arm.” — Dr. John J. Russell [19:54]

• On real-world studies vs. RCTs:

  “It just tries to mimic or emulate a randomized trial. But don’t let that fancy name fool you. It’s still an observational trial.” — Dr. Neal Skolnick [24:19]

• On GLP-1 and vision:

  “They found that no one was at increased risk of anything that lost their vision.” — Dr. John J. Russell [30:36]

Timestamps for Key Segments

• Intro & Article Rundown: [00:02–00:29]
• AI in Retinopathy Detection: [00:29–06:07]
• Orforglipron (ATTAIN-2 Trial): [06:10–11:12]
• FDA Suicidal Ideation Label Removal for GLP-1s: [11:12–17:14]
• Statins and CV Risk in Diabetes: [20:43–25:04]
• GLP-1s and Vision Threat: [25:04–32:37]
• Closing & Further Resources: [32:37–33:29]

Conclusion

This episode offers practicing clinicians clarity on the latest evidence in diabetes care and therapeutics, with practical context and critical appraisal. From AI diagnostic advances to the expanding future of oral GLP-1s, ongoing regulatory revisions, and nuanced safety discussions—this month’s Core Update underscores the dynamic and evidence-based nature of modern diabetes care.

For references and access to the discussed articles, visit:
www.diabetesjournals.org