Diabetes Core Update – September 2025

American Diabetes Association | Hosts: Dr. Neil Skolnik & Dr. John J. Russell | Release Date: September 4, 2025

Brief Overview

This episode of Diabetes Core Update provides a thorough review of recent high-impact studies on obesity treatment, diabetes therapy innovations, and practical nutrition guidance for patients on GLP-1 agonists. Special attention is given to combining new weight loss medications, advancements in insulin therapy, optimizing GLP-1 regimens, and the essential but often overlooked topic of protein intake and resistance training for patients losing weight. The episode is fast-paced, evidence-focused, and notable for its practical, clinic-ready insights.

Key Discussion Points & Insights

1. Cagrolintide and Semaglutide Combination for Obesity

[01:38 – 04:03]

• Study Design:
  Phase 3, 68-week, double-blind, placebo- and active-controlled trial in adults with overweight/obesity (no diabetes).
• Intervention:
  Four-arm randomization: combination of cagrolintide and semaglutide 2.4mg, semaglutide alone 2.4mg, cagrolintide alone 2.4mg, and placebo; all received lifestyle interventions.
• Results:
  • Combo group achieved an average 20.4% weight loss from baseline, vs. 3% with placebo.
  • Greater likelihood of achieving ≥5%, ≥20%, ≥25%, ≥30% weight loss vs. placebo.
  • 79.6% of combo group experienced GI side effects (mostly mild/transient), vs. 39.9% for placebo.
• Memorable Quote:
  • “Wow, this is exciting. Another medicine that we are now seeing that has over 20% weight loss…” – Neil [04:03]
  • “Amylin… is a satiety hormone… released from the pancreas in response to nutrient intake and it works in the hypothalamus to dampen appetite.” – Neil [04:46]
• Metabolic Impact:
  • 87% of prediabetic, obese subjects achieved normoglycemia.
  • Mean systolic BP reduction: 9.9 mmHg; diastolic: 5 mmHg.
  • In people with diabetes (Redefine 2), 13.7% weight loss and 73% achieved A1c <6.5%.

2. Once-Weekly Icosama vs. Multiple Daily Insulin for Type 2 Diabetes

[04:08 – 12:41]

• Study Design:
  Phase 3, open-label, 52-week non-inferiority trial comparing once-weekly icosama (combo of weekly basal insulin icodec + semaglutide) vs. standard basal-bolus insulin (daily glargine + 2-4x daily aspart).
• Key Outcomes:
  • A1c reduction: -1.47% with icosama vs. -1.40% with basal-bolus (non-inferior).
  • Body weight: icosama users lost ~15 pounds more.
  • Hypoglycemia episodes: 0.21/year (icosama) vs. 2.23/year (basal-bolus), p<0.0001.
  • Injection burden: ~8 injections/week (icosama) vs. 28/week (basal-bolus); saving approx. 1,400 injections/year.
• Memorable Quote:
  • “...to get down to eight shots a week from 28 shots a week. Right? So you're saving over a thousand shots a year.” – John [10:26]
  • “...you’re losing 15 pounds at the back end, you’re having less hypoglycemia…” – John [11:58]
• Practical Application:
  An encouraging development for simplifying intensive insulin regimens and improving adherence in poorly controlled T2D.

3. Nutrition Priorities for GLP-1 Therapy: Expert Interview with Aaron Skolnick, PTA, CPT

[12:41 – 20:08]

• Background:
  Focus on patients using GLP-1s for obesity—20–30% of Aaron’s training clients are on GLP-1s.
• Protein Intake & Sarcopenia:
  • Most clients (especially older adults) consume less than the recommended protein, at increased risk for muscle loss during weight loss.
  • “...when you’re in a caloric reduction, this is going to lead to even more severe muscle loss.” – Aaron [13:53]
• Practical Nutrition Guidance:
  • Nutrient deficiencies (esp. protein) are a key risk as calorie intake drops; most lack sufficient protein.
  • “All you need to do is just eat smart. Just veggies, fruits, variety colors, enough protein, that's helpful.” – Aaron [16:01]
  • Supplements are helpful, but “they are indeed supplements.” [16:44]
  • Absolute protein intake recommendation: 80–120g per day for most during weight reduction (vs. standard 0.8g/kg/d); nutrient-dense, high protein food lists provided.
• Muscle Mass Preservation:
  • Resistance training is essential. Not all exercise is sufficient (“aqua aerobics... that's not going to help you maintain muscle mass” [18:06]).
  • New exercisers face effort/motivation barriers; motivational interviewing is key.
  • “Copious amounts of caffeine, they will not be able to sit still. But on a serious note, motivational interviewing. Getting down to the why, that's really the biggest thing...” – Aaron [19:54]
• Clinical Application:
  Nutrition and exercise counseling is crucial for patients on GLP-1s to maintain function and long-term metabolic health.

4. Gradual vs. Standard Titration of Semaglutide

[20:09 – 22:04]

• Study Design:
  26–week RCT; flexible, much slower titration schedule vs. label-recommended titration for semaglutide in T2D.
• Key Findings:
  • Discontinuation due to GI side effects: only 2% (flexible) vs. 19% (standard), p=0.005.
  • Less reported nausea and weakness.
  • Glycemic (A1c, BMI) outcomes similar between both groups.
• Memorable Quote:
  • “If you can slowly kind of put your foot in the ocean a little bit... you're going to have maybe a better time than jumping right in.” – John [22:04]
• Clinical Relevance:
  Patient-centered titration can keep people on GLP-1s longer with better tolerance, offering shared control over dosing.

5. Tirzepatide vs. Semaglutide for Obesity—Head-to-Head Study

[22:04 – 25:07]

• Study Design:
  Phase 3B, open-label, 72-week trial in adults with obesity (no T2D), comparing maximal tolerated doses of tirzepatide vs. semaglutide.
• Results:
  • Average weight loss: 20.2% (tirzepatide) vs. 13.7% (semaglutide).
  • Waist reduction: 18.7cm (tirzepatide) vs. 13cm (semaglutide).
  • More tirzepatide participants reached clinically significant weight-loss milestones.
  • GI events common but generally mild/moderate.
• Memorable Quote:
  • “...what an amazing journey it has been. We're actually comparing two medicines that are both far more powerful at weight loss than we ever would have thought we would see just a decade ago.” – Neil [25:07]
• Context & Regulatory Updates:
  • Semaglutide now FDA-approved for MASH with advanced fibrosis and for overweight/obesity with coronary artery disease.
  • Tirzepatide recently approved for OSA; studies ongoing for more indications.

Notable Quotes & Memorable Moments

• On innovations in insulin therapy:
  “A really exciting way to get our patients back to being euglycemic and maybe much earlier.” – John [12:05]

• On resistance training basics:
  “...when you’re looking to maintain muscle mass, you’re looking to work in a repetition range and effort range that is going to have you getting quite fatigued, somewhere between 6 and 10 repetitions.” – Aaron [18:06]

• On making behavior change stick:
  “Motivational interviewing. Getting down to the why, that's really the biggest thing that's so helpful.” – Aaron [19:54]

Important Timestamps

• [01:38] — Cagrolintide + Semaglutide: trial design, major findings
• [04:03] — Mechanisms of action; discussion of amylin
• [04:08] — Once-weekly ICOSAMA vs. basal-bolus insulin
• [10:26] — Reducing injection burden and clinical relevance
• [12:41] — Nutritional guidance for GLP-1 users (interview)
• [13:53–16:44] — Protein intake, vitamin/mineral supplementation
• [17:49–18:49] — Effective resistance training explained
• [19:54] — Motivational strategies for initiating exercise
• [20:09] — Gradual semaglutide titration: benefits for side effect reduction and adherence
• [22:04] — Tirzepatide vs. semaglutide: direct comparison results
• [25:07] — Reflections on head-to-head trial learning
• [27:00+] — Regulatory updates on approvals for obesity, MASH, and OSA

Clinical Takeaways

• New combinations and head-to-head trials are pushing the boundaries of obesity and diabetes treatment, offering greater efficacy and easier regimens than ever before.
• Nutrition—particularly protein intake—and real resistance training are essential adjuncts to medical weight loss.
• Gradual dose titration empowers patients and reduces discontinuation from side effects.
• Direct drug comparisons (tirzepatide vs. semaglutide) are now guiding therapy choices on efficacy and tolerability.
• The podcast will rebrand to Diabetes, Obesity and Cardiometabolic Update (DOC) to reflect its evolving content focus.

For article links and more details, visit diabetesjournals.org.