Diabetes Core Update – Episode Summary (10/10/2013)

Overview

In the October 10, 2013 episode of Diabetes Core Update, Dr. Neil Skolnik and Dr. John J. Russell review and discuss recent clinically relevant articles from ADA’s journals, focusing on their application in diabetes management for health professionals. Key topics include head-to-head medication trials, new delivery technologies, mechanisms of drug-induced hyperglycemia, trends in diabetes prevalence, and the impact of calorie restriction versus surgery in diabetes remission.

Key Discussion Points & Insights

1. Canagliflozin vs. Sitagliptin in T2D Patients Uncontrolled on Metformin + Sulfonylurea

[02:03–04:00]

• Study Summary:

  • Year-long, randomized, double-blind, placebo-controlled trial of 755 patients.
  • Patients on stable metformin and sulfonylurea received either canagliflozin (300 mg) or sitagliptin (100 mg).
  • Primary Endpoint: A1C change at 52 weeks.
  • Outcomes:
    • Canagliflozin showed non-inferiority and subsequent superiority to sitagliptin in A1C reduction: −1.03% vs. −0.66%.
    • Greater reductions in fasting plasma glucose, systolic BP, and weight with canagliflozin.
    • Adverse events similar, but higher genital mycotic infections and osmotic diuresis with canagliflozin.
    • Hypoglycemia rates were similar.

• Clinical Relevance & Commentary:

  • "Both these classes of agents are on the map as a what next choice... A good way to look at what to use when we choose our medicines is to reflect back on the ADA statement about treatment of hyperglycemia, where they said we ought to think about individualizing therapy according to five criteria: the effect of the medicines on weight, efficacy, hypoglycemia, side effects and cost.” – Dr. Neil Skolnik [04:00]
  • Canagliflozin showed a slightly better profile in weight loss and efficacy, though both meds remain valid options.

2. Implantable Exenatide Delivery (ITCA 650) vs. Twice-Daily Exenatide Injections

[04:01–08:19]

• Study Summary:

  • 24-week, open-label, phase 2 study in T2D patients on metformin.
  • Compared continuous exenatide delivery via the ITCA 650 implant (20/40/60/80 mcg/day) vs. standard injections.
  • Findings:
    • Similar, significant A1C reductions across all methods; up to 63% achieved A1C <7%.
    • The implant could deliver effective therapy over 6–12 months with a single application.

• Clinical Relevance & Commentary:

  • “This certainly has a James Bond type quality to it... it’s going to stay there for six to 12 months and it's going to bring your A1C down a point and a half.” – Dr. John Russell [08:19]
  • Discussion of procedural simplicity compared to prior implantable systems, potential for improved adherence and tolerability.

3. Antipsychotic-Induced Hyperglycemia Independent of Weight Gain

[08:19–11:13]

• Study Summary:

  • 9-day, controlled inpatient study with olanzapine, aripiprazole, or placebo in healthy adults.
  • Evaluated insulin sensitivity and glucose regulation after antipsychotic exposure.
  • Results:
    • Olanzapine (associated with weight gain): caused significant postprandial insulin, GLP-1, and glucagon elevations, plus insulin resistance.
    • Aripiprazole (metabolically sparing): induced insulin resistance, no effect on postprandial hormones.
    • Effects were present independent of weight change or psychiatric disease.

• Clinical Relevance & Commentary:

  • "It's not just the weight gain associated with antipsychotics that cause hyperglycemia, but it's a direct effect of the compounds on causing insulin resistance." – Dr. Neil Skolnik [11:13]
  • The widespread use of these drugs (5+ million in U.S., >$17B market) and expanding indications highlight importance of understanding these independent metabolic risks.

4. Lixisenatide as Add-On to Insulin in Uncontrolled T2D

[11:13–13:46]

• Study Summary:

  • Double-blind, placebo-controlled trial of lixisenatide (20 mcg) vs. placebo in 495 patients on long-term basal insulin.
  • Results:
    • Mean diabetes duration: 12.5 years; mean A1C: 8.4%.
    • A1C reduced by −0.4% compared to placebo, resulting mean A1C ~7.8% at 24 weeks.

• Clinical Relevance & Commentary:

  • “It really doesn't seem super duper exciting when you look at the numbers as an add-on agent on what it really did to A1Cs.” – Dr. John Russell [13:46]
  • Note: Manufacturer Sanofi withdrew the FDA application for further study, planning for resubmission.

5. Secular Trends in U.S. Adult Diabetes Prevalence (NHANES, 1988–2010)

[13:46–16:12]

• Study Summary:

  • Analysis of over 22,000 adults across periods (1988–1994, 1999–2004, 2005–2010).
  • Diabetes prevalence increased by 75% over two decades across all age groups.
  • Adjusted prevalence ratios highest in older adults.
  • After adjusting for BMI/waist/weight-to-height, increase significant only in adults 65+.

• Clinical Relevance & Commentary:

  • “There's an epidemic of obesity and diabetes occurring in this country... about a 10 year lapse between increase in obesity and diabetes.” – Dr. Neil Skolnik [16:12]
  • Influences include reduced physical activity, increased average calorie intake (+400 kcal/day vs. 20 years ago), and food environments.

6. Gastric Bypass vs. Diet Alone: Rapid Improvement in Diabetes

[16:12–19:26]

• Study Summary:

  • Patients scheduled for Roux-en-Y gastric bypass underwent controlled feeding pre- and post-surgery.
  • Pre-operative, calorie-restricted diet yielded greater daily glycemic improvement (weight loss: 7.5kg) than post-surgical matched-diet (weight loss: 4kg).
  • Suggests diet/caloric restriction might explain much of the rapid diabetes improvement usually attributed to surgery.

• Clinical Relevance & Commentary:

  • “Well, maybe that people take in less calories and... eating less calories and losing weight can actually have a big effect on their diabetes, but certainly this proves that it does.” – Dr. John Russell [19:26]
  • Highlights the challenge of replicating surgical benefit via lifestyle changes in real-world settings due to issues of adherence.

Notable Quotes & Memorable Moments

• On Individualizing Therapy Choices:

  • "We ought to think about individualizing therapy according to five criteria: the effect of the medicines on weight, efficacy, hypoglycemia, side effects and cost." – Dr. Neil Skolnik [04:00]

• On Device Advancements:

  • “A James Bond type quality to it... just think, put medicine under the skin and it stays there for six to twelve months and brings A1C down a point and a half.” – Dr. John Russell [08:19]

• On Antipsychotic Risks:

  • "It's not just the weight gain... it's a direct effect of the compounds on causing insulin resistance." – Dr. Neil Skolnik [11:13]

• On the Diabetes Epidemic:

  • “Currently about a third of adults are obese, another third are overweight... Projections of diabetes currently are such that of every three infants born this year, one... will develop diabetes at some point during their lifetime.” – Dr. Neil Skolnik [16:12]

• On Caloric Restriction vs. Surgery:

  • “Maybe... eating less calories and losing weight can actually have a big effect on their diabetes, but certainly this proves that it does.” – Dr. John Russell [19:26]

Important Segment Timestamps

• Introduction & Article Overview: 00:56–02:03
• Canagliflozin vs. Sitagliptin: 02:03–04:00
• Implantable Exenatide Delivery: 04:01–08:19
• Antipsychotic-Induced Hyperglycemia: 08:19–11:13
• Lixisenatide Add-On: 11:13–13:46
• Secular Trends in Diabetes Prevalence: 13:46–16:12
• Gastric Bypass vs. Diet: 16:12–19:26

Conclusion

This episode offers key updates for clinicians on diabetes pharmacotherapy, technological advancements, drug safety considerations, and shifting epidemiology. The hosts emphasize the importance of individualized care, highlight the complex interplay between lifestyle, medication, and surgical intervention, and stress ongoing vigilance regarding the broader trends fueling the diabetes epidemic.