Diabetes Core Update – December 10, 2013

Episode Overview

This episode of Diabetes Core Update centers on key new research articles from the American Diabetes Association's main journals, focusing on advances in the management of Type 2 diabetes and addressing pivotal changes to cholesterol guidelines. Hosted by Dr. Neil Skolnik and Dr. John Russell, the discussion delivers clinically relevant insights for primary care physicians, covering:

• The inpatient use of sitagliptin for hyperglycemia
• Efficacy and safety data for empagliflozin (an SGLT2 inhibitor) as add-on therapy
• The problem of "clinical inertia" in intensifying diabetes treatment
• Significant changes in cholesterol management per the newest guidelines

Key Discussion Points and Insights

1. Sitagliptin for Inpatient Hyperglycemia

[01:31–03:07]

• Study Overview:
  A randomized, multi-center trial assessed sitagliptin (alone or with glargine) vs. basal-bolus insulin in 90 inpatients with Type 2 diabetes (controlled on diet, orals, or low-dose insulin).

  • Primary outcomes: Glycemic control (mean daily blood glucose), treatment failures, hypoglycemia rates.
  • Result: All regimens achieved similar glycemic control. Sitagliptin groups needed significantly less insulin and had no more hypoglycemia than the traditional basal-bolus regimen. Length of stay and treatment failures were similar.

• Clinical Context (Dr. Neil Skolnik):

  • Early 2000s studies on aggressive inpatient blood sugar management (notably in ICUs) sparked protocols for intensive insulin use. Later research, including the NICE-SUGAR trial, found intensive control increased risk—leading to ADA recommendations (blood glucose <180 mg/dL as a reasonable inpatient target).
  • This study suggests sitagliptin may have a role in inpatients (“it’s on the map to keep an eye out for future studies”) but is not ready to replace standard insulin therapy (“for now, I probably wouldn’t be using this in place of our usual insulin regimens”).

• Notable Quote:
  “Sitagliptin is a potentially attractive agent for inpatient hyperglycemia because of its lack of hypoglycemic effects, which might be the issue that leads to poor outcomes when patients are managed to try to achieve intensive blood sugar control.”
  — Dr. Neil Skolnik [04:27]

2. Empagliflozin as Add-on to Metformin + Sulfonylurea

[03:07–06:59]

• Study Design:

  • Patients inadequately controlled (A1C 7–10%) on metformin+SU received empagliflozin (10mg/25mg) or placebo for 24 weeks.
  • Empagliflozin groups saw A1C reductions: −0.82% (10mg), −0.77% (25mg), vs. −0.17% for placebo; five-pound weight loss was noted; significant systolic BP lowering.

• Side Effects:

  • Increase in urinary tract infections (esp. women), and genital infections (4x rise in women).

• Clinical Pearls (Dr. John Russell):

  • SGLT2 inhibitors likely to be used as third-line agents.
  • “About 0.8 A1C reduction… so not necessarily as potent as some other things, not as weak as some other things.”
  • These agents do not alone cause hypoglycemia, but the risk is increased when added to a sulfonylurea.
  • Cost and insurance coverage remain a challenge.

• Notable Quote:
  “This newer class of medicine... probably looked at it in the method that I think in primary care we would end up using this medicine and probably as a third line agent...”
  — Dr. John Russell [06:59]

3. Clinical Inertia in Type 2 Diabetes Management

[06:59–10:31]

• Study Data:

  • Retrospective cohort (81,000+ UK patients, 2004–2011).
  • Mean time to therapy intensification after uncontrolled A1C (>7%):
    • On 1 agent: 2.9 years
    • On 2 agents: 7.2 years
    • Insulin added on average 6–7 years after ongoing oral therapy, at high A1C thresholds (8.7–9.7%).

• Clinical Insight (Dr. Neil Skolnik):

  • Parallels “therapeutic inertia” seen in hypertension management: “People had six or more elevated blood pressure readings before their physician would increase antihypertensives.”
  • “We try to assess blood sugar control and we don't fool ourselves that further desire will lead to a better outcome. It often requires further changes in medications.”
  • Encourages shorter timeframes before intensifying therapy instead of prolonged observation.

• Notable Quote:
  “For patients who are on a single medicine, takes about two years of being out of control until we add a medicine. For patients on two or more oral agents, it’s over seven years... and clearly that’s too long.”
  — Dr. Neil Skolnik [10:31]

4. New Cholesterol Guidelines

[10:31–17:42]

• Key Updates:

  • The NIH has delegated guideline production to the American Heart Association (AHA); new AHA guidelines published ~10 days prior.

  • Randomized trials support statins but not specific LDL targets; so the new guidelines abandon LDL goals.

  • Instead, they recommend statin use in four groups:

    1. Clinical atherosclerotic CVD (including CAD, stroke, PVD).
    2. LDL ≥190 mg/dL.
    3. Diabetes, ages 40–75, LDL 70–189 mg/dL.
    4. Non-diabetics, no established disease, LDL 70–189 mg/dL, with 10-year ASCVD risk >7.5% (per new AHA calculator, not Framingham).

  • Statin therapy is stratified by intensity, not by an LDL target.

• Diabetes-Specific Implication (Dr. John Russell):

  • Not all diabetics automatically qualify for statin therapy anymore—age and LDL now limit eligibility.
  • High-dose statins (like atorvastatin, rosuvastatin) favored for diabetic patients fitting criteria.
  • Consideration of statin-induced diabetes: new-onset diabetes risk for high-potency statins is 1 in 200; weigh risk for primary prevention in low-risk diabetics.

• Notable Quotes:

  • “There are no more LDL targets. We’re not aiming for an LDL less than 130 or 170, but rather the decision is to use a moderate potency statin or a high potency statin.”
    — Dr. Neil Skolnik [14:45]
  • “That person who is 35 or has an LDL of 50, you wouldn’t necessarily put them on a statin, which is different from before.”
    — Dr. John Russell [15:40]

Memorable Moments

• On therapeutic inertia:
  “We don't fool ourselves that further desire will lead to a better outcome. It often requires further changes in medications.”
  — Dr. Neil Skolnik [11:25]

• On cholesterol guidelines:
  “If you have someone with diabetes...that would be a significant risk group that you would put them on a high potency statin, expect to get around a 50% reduction.”
  — Dr. John Russell [16:05]

Timestamps for Important Segments

• [01:31] Sitagliptin in hospitalized Type 2 diabetes patients
• [03:07] Empagliflozin as add-on to metformin/sulfonylurea
• [06:59] SGLT2 inhibitor clinical implications and safety
• [06:59] Clinical inertia in diabetes pharmacotherapy
• [10:31] Commentary on inertia and parallels with hypertension management
• [10:31] New cholesterol guidelines and diabetes
• [15:26] Discussion on diabetes-specific statin recommendations

Conclusion

This concise update highlights how new evidence around diabetes medications and cholesterol management guidelines will directly impact everyday practice. The hosts repeatedly stress the need for proactive therapy intensification in diabetes, careful assessment of new pharmacologic options (weighing efficacy, safety, and patient context), and adapting to guideline shifts—especially the move away from LDL targets in cholesterol management.

For further reading, the discussed articles can be found at www.diabetesjournals.org.