Podcast Summary: Diabetes Core Update – December 2014

Hosts: Dr. Neil Skolnik and Dr. John Russell
Episode Date: November 24, 2014
Main Theme:
This episode covers the most impactful clinical studies published in ADA journals, focusing on the economic costs of diabetes, advancements in pharmacotherapy (notably GLP-1 receptor agonists and weight loss medications), risks of hypoglycemia, and real-world rates of diabetes remission. The discussion emphasizes both the clinical and economic ramifications of diabetes care, the expanding understanding of diabetes’ pathophysiology, and the importance of practical prevention strategies.

Key Discussion Points & Insights

1. The Economic Burden of Diabetes (Diabetes Care)

[01:00 – 03:16]

• Scope: Analysis of the cost implications of diabetes (diagnosed, undiagnosed, gestational, and prediabetes) in 2012.
• Data Sources: Nationwide insurance claims, Medicare files, and inpatient records.
• Findings:
  • Total economic burden in 2012 was over $322 billion: $244B in direct medical costs, $78B in lost productivity.
  • This represents a 48% increase from 2007 ($218B).
  • Nearly half of U.S. adults have diabetes or prediabetes.
  • The cost per American: >$1,000/year, or 5% of median family income.
  • Growth drivers: 27% attributed to increased prevalence and 14% to higher per-case costs.
• Clinical Takeaway:
  • Prevention (lifestyle modification) is vital. Medications matter, but widespread prevention to reduce prediabetes and diabetes onset is essential.
• Quote:
  • “We are in trouble. The increased cost going up over 45% over a five year period of time is not hard but impossible for this country to sustain.” — Dr. Neil Skolnik [03:16]

2. GLP-1 Receptor Agonists and Appetite/Reward Pathways (Diabetes)

[03:17 – 07:10]

• Study Design: Randomized, placebo-controlled fMRI trial on obese type 2 diabetics, obese non-diabetics, and lean individuals.
• Intervention: IV exenatide (GLP-1 RA) with or without a receptor blocker. Brain response to food images measured.
• Findings:
  • Obese subjects had higher activation in brain areas related to appetite and reward in response to food images.
  • Exenatide reduced food intake and decreased related brain activity; effect was blocked by antagonist.
• Clinical Relevance:
  • GLP-1s influence satiety centers, providing a neurobiological rationale for weight and appetite effects.
  • Reinforces the “Ominous Octet” model, in which the brain’s role in diabetes and obesity (satiety/reward) is now recognized.
• Quote:
  • “Now we're starting to see five other parts of the body...and one of those eight now is the brain and satiety...the GLP-1 medications can help impact that a little bit.” — Dr. John Russell [07:10]

3. Phentermine/Topiramate for Weight Loss & Glycemic Control (Diabetes Care)

[07:11 – 10:26]

• Design: 56-week RCT for phentermine/topiramate ER vs. placebo in type 2 diabetics.
• Primary Outcome: Change in A1C; post hoc analysis for a second large cohort.
• Findings:
  • Weight loss: 9.4% (drug) vs. 2.7% (placebo).
  • A1C reduction: -1.6% (drug) vs. -1.2% (placebo).
  • More patients reached A1C targets and needed fewer medications in the drug group.
  • Common side effects: paresthesias, constipation, insomnia.
• Clinical Takeaway:
  • Confirms dual benefit (weight & glycemic control); not just cosmetic, but translates into meaningful clinical changes.
  • Progression from prediabetes to diabetes is also robustly reduced in high-dose groups.
• Quote:
  • “We really are seeing this medicine work well not just to achieve significant weight loss, but also to achieve improvement in metabolic parameters, decreased progression of diabetes in patients with prediabetes as well as improvement in A1C.” — Dr. Neil Skolnik [10:26]

4. Hypoglycemia, Cardiovascular Events, and Inflammatory Markers (Diabetes Care)

[10:27 – 13:54]

• Cohort: >1,000 adults, ages 60–75 with type 2 diabetes, followed for four years.
• Key Data:
  • 8.2% reported severe hypoglycemia in previous year.
  • 9.3% had a new macrovascular event at follow-up.
  • Severe hypoglycemia doubled the odds of macrovascular events (OR 2.1), quadrupled for MI (OR 4).
  • Independent association, even controlling for inflammation (CRP, fibrinogen).
• Clinical Relevance:
  • Emphasis on appropriate medication choices for older adults—minimizing agents prone to hypoglycemia, especially sulfonylureas.
  • Guidelines support statins for all diabetics >40 for their anti-inflammatory and CV benefits, not just lipid lowering.
  • Targets must be individualized, less stringent for seniors.
• Quote:
  • “We need to be very mindful when we are choosing agents in senior citizens...the rate of hypoglycemia of any individual agent we give to a particular patient really needs to be paramount.” — Dr. John Russell [13:54]

5. Real-World Diabetes Remission Rates (Diabetes Care – Diabetes and Aging Study)

[13:55 – 17:58]

• Population: 122,000+ adults with type 2 diabetes in integrated care, tracked for up to seven years.
• Definitions:
  • Partial Remission: ≥1 year of A1C 5.7–6.4% without meds
  • Complete Remission: ≥1 year of A1C <5.7%
  • Prolonged Complete Remission: ≥5 years of A1C <5.7%
• Incidence:
  • Partial: 1.47%, Complete: 0.14%, Prolonged: 0.07% over 7 years.
  • New onset diabetes (<2 years): Higher, but still only 4.6%.
  • Predictors: Age >65, recent diagnosis, low baseline A1C, African American race, off medications.
• Clinical Perspective:
  • Real-world remission (<2%) is far below rates in intensive intervention studies (e.g. Look AHEAD), or after bariatric surgery (~70%).
  • Implies usual care is not effective at promoting lifestyle change or enabling medication withdrawal.
  • Calls for stronger emphasis/motivation in supporting poor lifestyle change in everyday practice; select patients may benefit from considering bariatric surgery.
• Quote:
  • “Remission rates under 2% in a community setting are really disappointing and are very different than what was achieved… in the Look Ahead trial…. I think what it’s saying is that we’re just not doing a terribly good job at promoting lifestyle change in our usual practices.” — Dr. Neil Skolnik [17:58]

Notable Quotes & Memorable Moments

• On Cost Implications: “We are in trouble. The increased cost going up over 45% over a five year period of time is not hard but impossible for this country to sustain.” — Skolnik [03:16]
• Ominous Octet & The Brain: “GLP-1 medications can help impact [satiety and brain response] a little bit… part of the ominous octet and…reasons GLPs have a pleomorphic effect.” — Russell [07:10]
• New Meds, Major Impact: “We really are seeing this medicine work well…significant weight loss…improvement in metabolic parameters, decreased progression of diabetes…” — Skolnik [10:26]
• Hypoglycemia Management in Seniors: “The rate of hypoglycemia… needs to be paramount.” — Russell [13:54]
• On Remission Reality: “Remission rates under 2% in a community setting are really disappointing...” — Skolnik [17:58]

Timestamps of Important Segments

• Economic Burden of Diabetes: [01:00 – 03:16]
• GLP-1 Agonists & Appetite/Reward: [03:17 – 07:10]
• Phentermine/Topiramate for Weight Loss: [07:11 – 10:26]
• Hypoglycemia & Macrovascular Events: [10:27 – 13:54]
• Diabetes Remission in Community Care: [13:55 – 17:58]

Overall Tone & Clinical Emphasis

The conversation is clinical and practical, often underscoring the hard realities of diabetes management—rising costs, under-realized prevention/behavior change, and the importance of evidence-based, patient-centered medication choices. Both Drs. Skolnik and Russell advocate for “prevention first,” careful selection and application of pharmacotherapy, and individualized patient care (especially in the elderly).

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