Diabetes Core Update October 2016 – Detailed Summary

Podcast: Diabetes Core Update
Hosts: Dr. Neil Skolnik & Dr. John Russell
Date: September 25, 2016
Episode Theme:
A review and discussion of recent clinically relevant articles published by ADA journals, providing insights for healthcare professionals who manage patients with diabetes. This episode focuses on dietary interventions, drug combination therapies, novel delivery forms for injectables, prevention in high-risk groups, the metabolic impact of bed rest, and the emerging use of combination injectable agents.

Main Discussion Points & Insights

1. Dietary Fat Composition in Type 2 Diabetes

Source: Diabetes Care, August Edition
Summary:

• Discussed a meta-analysis comparing high monounsaturated fatty acid (MUFA) diets versus high-carbohydrate and high-polyunsaturated fatty acid diets in patients with type 2 diabetes.
• 24 studies (over 1,400 participants) compared high MUFA to high-carb diets; additional 4 studies compared to high PUFA diets.
• Findings:
  • High MUFA diets significantly reduced fasting plasma glucose, triglycerides, body weight, and systolic blood pressure.
  • Significant increases in HDL cholesterol.
  • Compared to high polyunsaturated fat diets, high MUFA diets notably reduced fasting plasma glucose.

Notable Quote:

"So a low fat diet that does not really look at carbs does not do as well as a Mediterranean diet, which is going to emphasize certain fatty acids."
— John Russell [03:24]

2. Initial Combination Therapy: Empagliflozin and Metformin

Source: Diabetes Care
Study Design:

• Drug-naive patients (A1C 7.5–12%, mean 8.6–8.9), randomized (n >1,300), 24-week study.
• Compared various combinations/doses of empagliflozin and metformin monotherapy vs. combination therapy.

Key Outcomes:

• Combination therapy reduced A1C by –1.9 to –2.1% (twice daily dosing) vs. –1.2 to –1.8% with metformin monotherapy.
• Weight reductions were also greater (–2.8 to –3.8 kg for combo vs. –0.5 to –1.3 kg for metformin alone).
• Adverse event rates similar; no severe hypoglycemia.

Clinical Implications:

• Early, aggressive combination therapy may prevent prolonged periods of uncontrolled hyperglycemia (metabolic memory/legacy effect).
• Reflects emerging paradigm toward initial combo therapy to achieve and sustain glycemic targets.

Notable Quotes:

"The idea of having better control early on that is more sustainable is very important here."
— Neil Skolnik [05:57]
"...Keeping people in good control early on with combination therapy is the beginning of what may become a new paradigm of care."
— Neil Skolnik [07:08]

3. Exenatide Once-Monthly Suspension: New Injectable Option

Source: Diabetes Care
Study Design:

• Phase 2 RCT, patients randomized to exenatide (2mg weekly or 5/8/11mg monthly) for 20 weeks.

Key Findings:

• All exenatide regimens reduced A1C significantly; differences among monthly doses were not significant.
• Weight reductions seen with all.
• No increase in adverse events, even with monthly dosing.

Clinical Takeaway:

• Once-monthly injectable potentially aids patients who are reluctant to self-inject or fail to adhere to daily/weekly regimens.
• Could facilitate provider-administered injections during office visits, improving access and adherence.

Notable Quote:

"You could imagine something that...you come into the office and...we give you a shot in the office once a month. So suddenly all these people who really couldn't bring themselves to give a shot...suddenly we can capture them."
— John Russell [10:12]

4. Pioglitazone to Prevent Diabetes in Post-CVA/TIA, Insulin-Resistant Patients

Source: Diabetes Care
Study Design:

• 3,800 patients post-ischemic stroke/TIA, insulin resistance but no diabetes, randomized to pioglitazone or placebo for ~4.8 years.

Key Outcomes:

• Pioglitazone group: 3.8% developed diabetes vs. 7.7% on placebo (Hazard Ratio: 0.48).
• Effect most pronounced in those with impaired fasting glucose.

Extended Context:

• The prior IRIS trial showed pioglitazone in this population also reduced recurrent stroke/MI by 25%.

Clinical Implication:

• For post-stroke/TIA patients with prediabetes, pioglitazone reduces progression to diabetes and offers CV protection; may guide post-event pharmacologic strategies.

Notable Quote:

"So for essentially the group included in this study, patients who are post CVA or TIA with prediabetes, I don't see any reason not to...use pioglitazone."
— Neil Skolnik [12:54]

5. Bed Rest’s Impact on Muscle, Insulin Resistance, and Recovery

Source: Diabetes
Study Design:

• 10 healthy young males, 1 week of strict bed rest; measures pre- and post-immobilization: muscle mass, strength, VO2 peak, insulin sensitivity.

Key Results:

• Lean muscle mass down 1.4 kg (2.5% decrease), quadriceps area down 3%.
• VO2 peak and muscle strength declined ~6–7%.
• Marked 30% decrease in whole-body insulin sensitivity (akin to 30–40 years of pancreatic aging).

Clinical Perspective:

• Even brief immobility spells in young, healthy patients lead to significant metabolic/functional changes.
• Extrapolated implications for elderly/hospitalized or immobilized patients: may emerge with increased insulin needs due to acquired resistance.

Notable Quotes:

"You lose about 2% of your muscle mass every day you lie in bed. And this reinforces this."
— John Russell [15:47]
"That level of insulin resistance...is equivalent to 30 to 40 years of aging of our pancreas."
— John Russell [16:50]

6. Basal Insulin + GLP-1 Receptor Agonists: A Complementary Combination

Source: Diabetes Spectrum (Review Article)
Summary:

• Basal insulin and GLP-1RAs have complementary mechanisms:
  • Basal insulin: Reduces fasting glucose, increases weight, hypoglycemia risk.
  • GLP-1RA: Lowers fasting/postprandial glucose (agent-dependent), reduces weight, GI side effects, minimal hypoglycemia.
• Meta-analysis (15 studies, 4,300+ patients): Adding GLP-1 RA to basal insulin further lowered A1C (by 0.44%) and reduced weight (by 3.2 kg), without higher hypoglycemia risk vs. insulin alone.

Emerging Therapies:

• Fixed-ratio co-formulations (insulin degludec/liraglutide, insulin glargine/lixisenatide) pending FDA review.

Clinical Relevance:

• Many patients on insulin don’t achieve glycemic targets; combo treatments offer:
  • Greater efficacy
  • Weight control or loss instead of gain
  • No increase in hypoglycemia
  • Fewer GI side effects vs. GLP-1 alone
• May be optimal for patients failing oral therapy or those not controlled on either class alone.

Notable Quotes:

"The concept of combination therapy with basal insulin and a GLP1 is really an incredibly exciting thing..."
— Neil Skolnik [20:14]
"Using this as a combination potentially allows us an opportunity to have better efficacy with less side effects than we would have using either one alone."
— Neil Skolnik [21:07]

Key Timestamps for Important Segments

• [00:55] Overview of articles discussed
• [03:24] Mediterranean vs. low-fat diet for type 2 diabetes
• [05:57] Combination empagliflozin/metformin therapy and its practice implications
• [10:12] Exenatide once-monthly: addressing injectable therapy barriers
• [12:54] Prevention of diabetes with pioglitazone after stroke/TIA
• [15:47] Impact of bed rest on muscle mass & insulin resistance
• [19:41] Basal insulin + GLP-1RA: complementary mechanisms, clinical synergy
• [20:14] Future of fixed-ratio combination injectables

Memorable Moments & Notable Quotes

• "A low fat diet that does not really look at carbs does not do as well as a Mediterranean diet, which is going to emphasize certain fatty acids." — John Russell [03:24]
• "The idea of having better control early on that is more sustainable is very important here." — Neil Skolnik [05:57]
• "You could imagine something...we give you a shot in the office once a month. So suddenly all these people who really couldn't bring themselves to give a shot...suddenly we can capture them." — John Russell [10:12]
• "For...patients who are post CVA or TIA with prediabetes, I don't see any reason not to...use pioglitazone." — Neil Skolnik [12:54]
• "You lose about 2% of your muscle mass every day you lie in bed. And this reinforces this." — John Russell [15:47]
• "The concept of combination therapy with basal insulin and a GLP1 is really an incredibly exciting thing..." — Neil Skolnik [20:14]

Conclusion

This episode of Diabetes Core Update provides actionable insights into diet composition, the value of earlier and more strategic combination pharmacotherapy, emerging long-acting injectables and new fixed-ratio combinations, as well as the crucial metabolic consequences of hospitalization-related immobility. Each article discussion not only bridges research with clinical application but also anticipates coming changes in diabetes management paradigms.

For links to full articles and more information, visit: www.diabetesjournals.org