Diabetes Core Update – December 2015

Podcast: Diabetes Core Update
Host: American Diabetes Association
Episode Date: November 24, 2015
Presented by: Dr. Neil Skolnik & Dr. John Russell

Episode Overview

In this December 2015 episode, Drs. Neil Skolnik and John Russell highlight and discuss several recent clinically relevant articles from the American Diabetes Association’s journals. The main topics include new research on SGLT2 inhibitors in type 1 and type 2 diabetes, comparative effectiveness of injectable therapies, depression in youth with diabetes, nuances in insulin administration, and emerging science on the microbiome’s role in diabetes risk and management.

This episode is intended for practicing clinicians, with practical takeaways that can inform real-world diabetes management.

Article Discussions & Key Insights

1. SGLT2 Inhibitors as Add-On to Insulin in Type 1 Diabetes

[00:55-03:40]

• Study: 18-week, double-blind phase 2 study evaluating canagliflozin (100 mg and 300 mg) vs. placebo in 351 adults with type 1 diabetes on insulin.
• Key Findings:
  • A1C reduction ≥4% and no weight gain: 41% (canagliflozin) vs. 14% (placebo) at week 18
  • Both doses improved A1C, decreased body weight and insulin dose.
  • Adverse Effects: Increased diabetic ketoacidosis (DKA): 4.3% (100mg), 6% (300mg), 0% (placebo)

Dr. Russell [03:16]: “The whispers that we had heard about this ketoacidosis that happens with SGLT2…not only does it happen, it happens a pretty significant amount of time… So certainly the juice is not worth the squeeze.”

Clinical Takeaway:
Cautious approach urged—benefits are modest and risk for DKA is significant in type 1 diabetes.

2. Once-Weekly Dulaglutide vs. Insulin Glargine in Type 2 Diabetes (on Metformin & Glimepiride)

[03:41-06:03]

• Population: 810 patients; mean baseline A1C 8.1%, randomized to dulaglutide or glargine + metformin/glimepiride; 78-week trial.
• Outcomes:
  • A1C reduction higher with dulaglutide (-1.08% high dose, -0.76% low dose) vs. glargine (-0.63%)
  • Weight decreased with dulaglutide, increased with glargine.
  • Lower total hypoglycemia and severe hypoglycemia minimal in both groups.
  • More GI side effects (nausea, diarrhea) with higher dulaglutide doses.

Dr. Skolnik [06:04]: “This further supports the recommendations of GLP1s as an option instead of insulin as add on to oral hypoglycemics… We see again that there is weight loss instead of weight gain and a low incidence of hypoglycemia.”

Clinical Takeaway:
Supports GLP-1 agonists (e.g., dulaglutide) as preferable third-line injectables over basal insulin in patients inadequately controlled on metformin + sulfonylurea.

3. History and Mechanism of SGLT2 Inhibitors: From Bench to Bedside

[06:04-11:20]

• Content: A narrative review tracing the origins of SGLT2 inhibitors from the discovery of phlorizin in apple bark 200 years ago to modern FDA-approved drugs (dapagliflozin, canagliflozin, empagliflozin).
• Mechanistic Highlights:
  • SGLT2 inhibitors block renal glucose reabsorption, leading to glucosuria and lower blood glucose.
  • SGLT2 is kidney-specific; SGLT1 also found in intestine, heart, muscle—SGLT1 inhibition causes diarrhea.
  • Low hypoglycemia risk due to action only when hyperglycemic.

Dr. Russell [11:21]: “The category of our oldest diabetes medicine is now one that we’re finding new and interesting ways to incorporate into our patients’ care for type 2 diabetes.”

Clinical Takeaway:
SGLT2 inhibitors are foundational in diabetes management after metformin; fascinating history; ongoing evolution in their clinical utility.

4. Depressive Symptoms in Youth with Type 1 or 2 Diabetes

[11:21-13:22]

• Study: Screening 600 children (ages 10–17) for depression using the Children’s Depression Inventory.
• Results:
  • 13% of type 1, 22% of type 2 diabetes youth had depressive symptoms.
  • Only small fractions received treatment (4% T1D, 9% T2D).
  • In T1D, depressive symptoms correlated with lower income and obesity.

Dr. Skolnik [13:23]: “This is important because this expands the information that we have about depression in patients with diabetes in adults to the pediatric population…most of the patients with depression…are not identified.”

Clinical Takeaway:
Emphasizes the need for routine depression screening in pediatric diabetes care.

5. Inhaled Insulin (Technosphere) vs. Subcutaneous Aspart in Type 1 Diabetes

[13:22-16:22]

• Study: Open-label, 24-week non-inferiority trial comparing inhaled technosphere insulin to injectable aspart (both with basal insulin).
• Key Results:
  • Similar A1C reduction (technosphere: -0.21%; aspart: -0.4%).
  • More aspart patients reached A1C <7% (31% vs 18%).
  • Inhaled insulin associated with weight loss, lower hypoglycemia rate.
  • Main adverse effect: mild cough (32% technosphere; 2% aspart); 5% discontinuation.

Dr. Russell [16:22]: “Figuring out a way to do it [deliver insulin] without having to cause a little pain for the patients… is a little bit of the holy grail of diabetes research.”

Clinical Takeaway:
Inhaled insulin offers a needle-free, portable option with weight loss and less hypoglycemia, though minor cough and slightly less A1C efficacy versus aspart.

6. Importance of Proper NPH Insulin Resuspension

[16:22-19:25]

• Study: Compared NPH insulin absorption/action following proper resuspension vs. various non-resuspended positions.
• Findings:
  • Huge variability in pharmacokinetics/dynamics if pens/vials are not resuspended properly.
  • Correct technique: at least 20 gentle turns (1.5 minutes), which most patients likely don’t do.

Dr. Skolnik [19:26]: “…A large difference in insulin delivery depending on whether patients resuspended their medicines correctly…Reminds me of the importance of having patients see a certified diabetes educator…”

Clinical Takeaway:
Meticulous preparation of NPH insulin is essential for consistent glucose control; reinforce technique with patients.

7. Diabetes and the Microbiome—Symposium Review

[19:26-23:08]

• Overview: Review of symposium data showing microbiome-gut interactions’ role in type 1 & type 2 diabetes.
• Key Points:
  • Probiotics can modify T1D course in mice; increased antibiotic use may be linked to diabetes.
  • Mouse studies: gut microbiota transfer can affect insulin resistance, glucose signaling, and obesity.
  • Gender, hormones and microbiota interaction can affect autoimmunity.
  • Manipulating microbiome could become a future therapeutic avenue.

Dr. Russell [23:09]: “It’s a little bit scary. It seems like I’ve seen enough sci-fi movies that kind of started this way… But it certainly seems to be a new frontier that is just opening up.”

Clinical Takeaway:
Emerging science; be mindful of microbiome health in practice (e.g., judicious use of antibiotics). Potential for future microbiome-targeted diabetes interventions.

Notable Quotes & Memorable Moments

• “The juice is not worth the squeeze.” — Dr. John Russell on SGLT2 inhibitors’ risk/benefit in type 1 diabetes [03:32]
• “We see again that there is weight loss instead of weight gain and there's a low incidence of hypoglycemia.” — Dr. Neil Skolnik on GLP1s vs. insulin [06:04]
• “This is a real issue for many of our patients with diabetes… most of the patients with depression and pediatrics are not identified.” — Dr. Neil Skolnik [13:23]
• “It’s a little bit scary… but it certainly seems to be a new frontier that is just opening up.” — Dr. John Russell on the microbiome [23:09]

Timestamps for Key Segments

• 00:55–03:40 — SGLT2 inhibitors in type 1 diabetes
• 03:41–06:03 — Dulaglutide vs. glargine as third-line injectables
• 06:04–11:20 — SGLT2 inhibitors: origin and mechanism
• 11:21–13:22 — Depression in youth with diabetes
• 13:22–16:22 — Inhaled insulin vs. subcutaneous aspart
• 16:23–19:25 — NPH insulin: significance of proper resuspension
• 19:26–23:08 — Microbiome and diabetes: research symposium

Clinical Takeaways

• Be cautious with SGLT2 inhibitors in type 1 diabetes due to risk of DKA.
• GLP-1 agonists as third-line therapy can outperform basal insulin for A1C and weight outcomes with less hypoglycemia.
• Ask about depression routinely in youth with diabetes; most with depressive symptoms are untreated.
• Inhaled insulin offers a promising, convenient alternative to injections.
• Reinforce proper insulin handling and injection techniques with all patients, especially those on NPH.
• Microbiome research is rapidly expanding—future diabetes management may include gut-targeted strategies.

For full article access and more, visit: www.diabetesjournals.org