Diabetes Core Update: Special Edition – Medical Management of Hyperglycemia (January 2015)

Podcast: Diabetes Core Update
Date: January 30, 2015
Host: Dr. Neil Skolnik
Guest: Dr. Silvio Inzucchi, Co-chair of the ADA/EASD Hyperglycemia Management Position Statement, Yale Diabetes Center

Overview

This special edition of the Diabetes Core Update podcast covers the January 2015 ADA/EASD position statement “Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach.” Dr. Neil Skolnik interviews Dr. Silvio Inzucchi, a co-chair of the committee that authored the update. The episode reviews highlights of the 2015 update, focusing on individualized glycemic goals, the role of lifestyle modification, updates on pharmacologic options, and the rationale behind new recommendations.

Key Discussion Points & Insights

1. Patient-Centered Approach to Glycemic Targets

Timestamps: 03:53–05:46

• The guidelines reinforce individualization of glycemic goals based on patient characteristics.
• Aggressiveness of treatment should consider age, comorbidities, duration of diabetes, and life expectancy.
• For younger, healthier patients, stricter goals (A1c ≈ 7%) are reasonable. For elderly and those with significant comorbidities, less stringent targets are safer.
• The main benefit of glucose control is reduction in microvascular risk. The effect on macrovascular risks remains less certain.
• Special emphasis on avoiding hypoglycemia in high-risk groups.

"The approach in a newly diagnosed individual in their mid-40s will be different from someone who begins treatment in their mid-80s."
— Dr. Silvio Inzucchi (03:57)

2. Role of Lifestyle Modification and Initial Pharmacotherapy

Timestamps: 06:31–07:42

• The 2015 update softens prior recommendations that all patients start metformin immediately upon diagnosis.
• Lifestyle modification is strongly encouraged as first-line when possible.
• If a patient can attain target glycemia with lifestyle alone, pharmacologic therapy may be delayed.

"If you have patients who are doing well with lifestyle changes alone, [there’s] no reason to move to pharmacotherapy until you have to."
— Dr. Silvio Inzucchi (07:28)

3. Metformin Use and Renal Function

Timestamps: 08:55–12:20

• Discussion of metformin’s safety profile in patients with chronic kidney disease (CKD).
• The panel recommends using estimated GFR (eGFR) over creatinine for dosing decisions, aligning with UK’s NICE guidelines.
  • Continue metformin if eGFR >45.
  • Halve dose if eGFR 30–45.
  • Discontinue if eGFR <30.
• FDA guidelines (based on serum Cr) may be too conservative.

"Many of us have petitioned the FDA to reassess these guidelines to see if, number one, could we base them more on estimated GFR as opposed to simply creatinine."
— Dr. Silvio Inzucchi (10:21)

• The risks with metformin are far lower than historic concerns (mainly attributed to the older biguanide, phenformin).

4. Approach to Marked Hyperglycemia

Timestamps: 12:56–15:26

• For newly diagnosed patients with very high A1c (>9%) or significant hyperglycemia, consider dual therapy from the outset.
• Basal insulin is preferred if blood glucose is very high (e.g., >350 mg/dL or A1c >10–11%), or if symptomatic.
• Once stabilized, can attempt to transition to oral agents.

"We don't want people to start metformin monotherapy in patients who present with blood sugars of 400. That just doesn't make sense and it's potentially dangerous."
— Dr. Silvio Inzucchi (15:15)

5. Updates on Specific Drug Classes

Timestamps: 16:35–23:49

a. Thiazolidinediones (TZDs) and Bladder Cancer

• Early data suggested bladder cancer risk with pioglitazone, but more recent long-term studies (Kaiser Permanente, European data) do not support this risk.
• The potential for benefit remains for appropriate patients, especially now that TZDs are generic and affordable.

"So I think at this point there are more papers suggesting no risk at all than those that had indicated a small increase in risk."
— Dr. Silvio Inzucchi (18:42)

b. Incretin Therapies (DPP-4 inhibitors, GLP-1 receptor agonists)

• Recent reviews by the FDA and EMA do not support an increased risk for pancreatic neoplasia or pancreatitis.
• More long-term data pending, but current evidence lessens concern over pancreatic risks.

c. SGLT2 Inhibitors

• Recognized as a class with evidence for A1c reduction, modest weight loss, and blood pressure lowering.
• Now equally considered as an option for dual therapy after metformin, alongside sulfonylureas, TZDs, DPP-4 inhibitors, GLP-1 agonists, and basal insulin.
• Expense and individual patient factors should be weighed.

"Now we have six credible drug choices after metformin."
— Dr. Silvio Inzucchi (22:41)

• Cost remains a significant concern, especially as newer agent classes are 100x more expensive than generics but not 100x more effective.

6. When to Add Insulin, and the Role of Combinations

Timestamps: 23:49–29:59

• Insulin can be considered after metformin (dual therapy), but many patients prefer to exhaust oral options first.
• Basal insulin is the initial recommended insulin strategy.
• For patients uncontrolled on multiple agents, adding basal insulin is usually necessary.
• GLP-1 receptor agonist + basal insulin is now a highlighted combination:
  • Similar (even superior) efficacy to basal-plus-mealtime insulin.
  • Less risk of hypoglycemia.
  • Greater benefit for weight loss.

"Basal insulin plus GLP1 receptor agonist... this combination has now been demonstrated to be as effective and without as many side effects as adding three mealtime insulin injections."
— Dr. Silvio Inzucchi (27:22)

• Practical consideration: high cost for GLP-1 agonists, balanced against reduced complexity (e.g., weekly injections) and improved side effect profile.

7. Summation and Paradigm Shifts

Timestamps: 30:06–31:14

• The 2015 update introduces significant shifts:
  • Reinforced emphasis on individualized care.
  • Expanded options after metformin.
  • Major role for basal insulin/GLP-1 agonist combination in complex cases.
  • Cost and patient preferences are central to all decisions.

Notable Quotes & Memorable Moments

• On patient-centered care:
  "We first have to have a very frank discussion with the patient and their families as to how aggressive to be."
  — Dr. Silvio Inzucchi (03:58)

• On lifestyle:
  "All of us who take care of patients can think of those individuals who really did a marvelous job of finally attending to diet and exercise and were able to control their diabetes without medicines."
  — Dr. Neil Skolnik (07:46)

• On metformin safety:
  "The incidence of lactic acidosis in metformin-treated patients is significantly lower than with phenformin. In fact, most studies have demonstrated that the risk is essentially the same as in untreated diabetic patients."
  — Dr. Silvio Inzucchi (10:58)

• On evolving drug options:
  “They [SGLT2 inhibitors] are about 100 times more expensive, and they're certainly not 100 times more effective... but I think we just have to be very realistic and incorporate these financial issues into our treatment decisions.”
  — Dr. Silvio Inzucchi (23:18)

• On GLP-1 and basal insulin combination:
  "The hemoglobin A1C reductions were essentially identical. In fact, in some studies there was a slight favor to the A1C reductions with the GLP1 basal insulin combination. In addition, there seem to be less hypoglycemia, which makes sense and also marked differences in weight."
  — Dr. Silvio Inzucchi (28:13)

Recommended Listening Segments (Timestamps)

• Patient-centered goal setting: 03:53
• Lifestyle therapy vs. immediate metformin: 06:31
• Metformin and renal function: 08:55
• Managing marked hyperglycemia: 12:56
• Drug safety updates (TZDs, incretins, SGLT2i): 16:35
• Advanced pharmacologic options and paradigm shifts: 24:20
• New strategies after basal insulin: 27:22

Conclusion

This episode provides a practical, current overview of the 2015 ADA/EASD hyperglycemia management guidelines, highlighting a patient-centered, flexible approach. It acknowledges the expanded armamentarium of diabetes medications, the need for individualized care, the newfound role of the basal insulin/GLP-1 agonist combination, and a frank discussion on the realities of cost and flexibility in therapy.

For more details, the full position statement is available at the American Diabetes Association’s website.