Consensus Statement Updated on Management of Hyperglycemia in Type 2 Diabetes

From Medscape Medical News
Laurie Barclay, MD

Diabetologia. Published online October 22, 2008.

Clinical Context

Good glycemic control can significantly lower morbidity rates related to type 2 diabetes and is therefore a vitally important treatment goal. Lowering and keeping glucose levels as close to the normal range as possible has been shown to reduce microvascular complications of diabetes, including retinopathy, nephropathy, and neuropathy.

In August 2006, the ADA and EASD published a consensus algorithm for the medical management of type 2 diabetes. An update in January 2008 specifically highlighted safety concerns regarding the thiazolidinediones, whereas this current update focuses on new classes of medications for which more clinical data and wider experience are now available.

Study Highlights

In type 2 diabetes, an important therapeutic goal is to achieve and to maintain hemoglobin A1c levels of less than 7.0%.

For most patients with type 2 diabetes, the initial treatment approach (tier 1, step 1) with well-validated therapies should include lifestyle intervention and use of metformin, titrated to its maximally effective dose at 1 to 2 months.

Lifestyle changes should aim to improve glucose levels, blood pressure, lipid levels, and weight control.

When tier 1, step 1 fails to achieve or maintain target glycemic goals, other medications should be added rapidly, and new regimens should be started.

If target hemoglobin A1c level is not achieved with step 1, or if metformin is contraindicated or poorly tolerated, step 2 is to add another medication, either insulin or a sulfonylurea.
Insulin, typically a basal (intermediate- or long-acting) insulin, is preferred for patients who have a hemoglobin A1c level of more than 8.5% or hyperglycemic symptoms.
Insulin plus metformin is a particularly effective means to lower glycemia while limiting weight gain.
In step 3, insulin therapy is started or intensified by giving additional injections, usually a short- or rapid-acting insulin given before selected meals, to reduce postprandial glucose levels.
Once insulin injections are started, insulin secretagogues (sulfonylurea or glinides) should be discontinued, or tapered and then discontinued.
In selected clinical settings, the tier 2 algorithm, which consists of less well-validated therapies, may be considered.
For patients with hazardous jobs that would make hypoglycemia particularly dangerous, exenatide or pioglitazone may be added, but rosiglitazone is not recommended.
Exenatide may be considered for patients who need to lose weight and in whom hemoglobin A1c level is close to target (< 8.0%).
If these interventions do not achieve target hemoglobin A1c levels or are not tolerated, tier 2 interventions should be stopped and basal insulin started.
The amylin agonists, alpha-glucosidase inhibitors, glinides, and dipeptidyl peptidase 4 inhibitors may be appropriate for selected patients.
However, they are not included in the 2 tiers of preferred agents because their efficacy to lower glucose is less or equivalent vs the first- and second-tier agents, they are relatively expensive, and clinical data regarding their use are limited.
Selecting individual agents should be based on their efficacy to lower glucose and on other characteristics.
When adding second antihyperglycemic medications, the synergy of particular combinations and other drug interactions should be considered.
Antihyperglycemic drugs with different mechanisms of action typically have the greatest synergy.

Pearls for Practice

In type 2 diabetes, an important therapeutic goal is to achieve and to maintain hemoglobin A1c levels less than 7.0%. For most patients, step 1 is lifestyle intervention and metformin. When this fails to achieve or maintain target glycemic goals, other medications should be added rapidly, and new regimens should be started. Step 2 is to add another medication, either insulin or a sulfonylurea. In step 3, insulin therapy is started or intensified.

The tier 2 algorithm using less well-validated therapies may be considered in selected patients. For those in whom hypoglycemia would be particularly dangerous, exenatide or pioglitazone may be added, but rosiglitazone is not recommended. Exenatide may be considered for patients who need to lose weight and in whom hemoglobin A1c level is close to target (< 8.0%),