Diabetes Core Update – August 2014 – Podcast Summary
Hosted by Dr. Neil Skolnik & Dr. John Russell – American Diabetes Association
Release Date: July 20, 2014
Duration: ~15 minutes

Overview

This episode of Diabetes Core Update reviews the latest research articles from ADA journals pertinent to front-line diabetes care. The hosts focus on new GLP-1 receptor agonists (albiglutide and dulaglutide), the evolving role of pharmacogenomics in metformin therapy, risks of diabetes with statin use, and methods for initiating and titrating prandial insulin in type 2 diabetes. The discussion emphasizes clinical relevance and applicability for healthcare professionals treating diabetes.

Key Discussion Points & Insights

1. Albiglutide – A Weekly GLP-1 Receptor Agonist

Sources: Two studies from Diabetes Care
Timestamps: [00:55]–[04:42]

• Efficacy/Safety Study:

  • 104-week randomized, double-blind trial in type 2 diabetics on metformin; compared albiglutide (30 mg), sitagliptin (100 mg), glimepiride (2 mg), and placebo.
  • A1C Reductions Over 104 Weeks:
    • Albiglutide: -0.9% vs. placebo, -0.4% vs. sitagliptin, -0.3% vs. glimepiride.
    • Baseline A1C was 8.1% across all groups.
  • Weight Change:
    • Albiglutide: -1.2kg; placebos and other arms saw less weight loss or weight gain (glimepiride: +1.17kg).
  • Side Effects: Diarrhea, nausea most common with albiglutide.

• Basal Insulin Add-On Study:

  • Compared adding weekly albiglutide to patients on basal insulin (glargine) vs. adding prandial insulin lispro three times daily.
  • At 26 weeks:
    • Albiglutide: -0.82% A1C; Lispro: -0.66%.
    • Albiglutide met non-inferiority; led to weight loss (vs. weight gain with lispro).

Notable Commentary:

• John Russell [04:42]:
  “If you ask our patients would you rather do something every Sunday versus take three shots a day... you could really see that people would want to do this. And also you see, you know, you could take a medicine that's going to help you lose weight versus taking more insulin that's going to make you put on weight. … A very exciting study for this newer medicine.”

2. Pharmacogenomics and Metformin Response

Source: Workshop review article from Diabetes
Timestamps: [06:46]–[10:30]

• Genetic variation significantly affects individual response to metformin.
• Today Study: adolescents have higher metformin failure rates than adults.
• GWAS (DARTS Study): Wide interindividual response; A1C reduction ranges from -4% to increased A1C post-treatment; strongest link with ATM gene variant (chromosome 11).
• Uptake of pharmacogenomic testing is low among US physicians (13% ordered in 6 months; only 29% trained during their education).
• Practical clinical application not yet feasible—interesting but not yet actionable.

Notable Commentary:

• Neil Skolnik [10:30]:
  “The bottom line for US clinicians is that this is interesting, will likely someday be important, but still is relegated to that future world of ideas that that really is not ready for implementation with our patients in the office.”

3. Statins and the Risk of Diabetes

Source: Large cohort study from Diabetes Care
Timestamps: [10:30]–[13:09]

• Followed over 100,000 new statin users in Italy, 2003–2010; outcome: new-onset diabetes.
• Higher statin adherence = higher diabetes risk:
  • Low, intermediate, high adherence: HRs 1.12, 1.22, 1.32.
  • Absolute risk: Treat 250 patients for 4 years = 1 extra diabetes case.
• The cardiovascular benefits of statins heavily outweigh diabetes risk.

Notable Commentary:

• John Russell [13:09]:
  “...patients come in here and say, I don’t want to take this medicine because it’s going to cause diabetes, but it certainly would be throwing the baby out with the bathwater.”

4. Dulaglutide – Another Weekly GLP-1 Receptor Agonist

Sources: Three studies from Diabetes Care
Timestamps: [13:09]–[18:55]

• Monotherapy vs. Metformin:

  • Dulaglutide superior to metformin for A1C reduction (~-0.78% vs. -0.56%); no severe hypoglycemia.

• Dulaglutide vs. Sitagliptin:

  • Dulaglutide (high dose): -1.1% A1C; sitagliptin: -0.39%.
  • Weight loss better with dulaglutide.

• Dulaglutide (add-on) vs. Exenatide:

  • Superior A1C lowering and less hypoglycemia with dulaglutide.
  • GI side effects (especially nausea) more common with higher dulaglutide dose.

Notable Commentary:

• Neil Skolnik [18:55]:
  “...dulaglutide versus metformin—dulaglutide has better A1C control. Dulaglutide versus sitagliptin—a DPP4 inhibitor—dulaglutide has better A1C control. And ... in a head to head trial with another weekly GLP1 receptor agonist ... dulaglutide has better A1C control... large numbers of patients. Well done trials. Impressive results... An exciting class to begin to get experience with.”

5. Titration of Prandial Insulin – Patient-Driven Algorithms

Sources: Randomized trial from Diabetes Care
Timestamps: [18:56]–[22:15]

• Compared two self-titration approaches for adjusting insulin lispro: daily vs. every-three-days.
• Both regimens achieved similar and significant reductions in A1C (~1%), with comparable hypoglycemia rates.
• Patient empowerment and intensive monitoring equally effective.

Notable Commentary:

• John Russell [22:15]:
  “Anytime we can empower our patients to be part of the decision making process about their own disease is clearly patient centered, and it’s clearly what we want to do for our patients.”

Memorable Quotes

• John Russell, on weekly GLP-1s [05:00]:
  “If you ask our patients would you rather do something every Sunday versus take three shots a day... you could really see that people would want to do this.”
• Neil Skolnik, on metformin pharmacogenomics [10:30]:
  “This is interesting, will likely someday be important, but still is relegated to that future world of ideas that that really is not ready for implementation with our patients in the office.”
• John Russell, on statin risk [13:09]:
  “[Stopping statins] would certainly be throwing the baby out with the bathwater.”
• Neil Skolnik, on dulaglutide [18:55]:
  “Well done trials. Impressive results, head to head with a number of different medications. An exciting class to begin to get experience with.”
• John Russell, on insulin self-titration [22:15]:
  “Anytime we can empower our patients to be part of the decision making process about their own disease is clearly patient centered, and it’s clearly what we want to do for our patients.”

Important Timestamps

• Albiglutide studies: [00:55]–[04:42]
• Metformin pharmacogenomics: [06:46]–[10:30]
• Statins and diabetes: [10:30]–[13:09]
• Dulaglutide studies: [13:09]–[18:55]
• Prandial insulin titration: [18:56]–[22:15]

Takeaway for Clinicians

• Weekly GLP-1 agonists (albiglutide, dulaglutide) are effective, promote weight loss, and have lower hypoglycemia risk; ease of use is attractive.
• Pharmacogenomics is rapidly advancing, yet clinical application in metformin selection remains on the horizon.
• Statins increase diabetes risk modestly, but benefits for cardiovascular disease overwhelmingly prevail.
• Empowering patients in insulin titration is safe and effective; frequent adjustment (daily or every three days) works.
• The field is rapidly evolving—new agents and head-to-head trials are critically shaping practice.