Management of Hyperglycemia in Type 2 Diabetes
The new joint position statement from the American Diabetes Association and the European Association for the Study of Diabetes emphasizes an individualized, patient-centered approach that is less prescriptive and algorithmic than previous guidelines.
Goals
The guidelines recommend lowering HbA1c to less than 7% in most patients. More important, however, is establishing an individual goal for each patient, taking into account the benefit and risk of tight glycemic control, and the patient’s ability to comply with recommended regimens.
For example, a patient who is newly diagnosed with type 2 diabetes, is highly motivated, is at low risk of hypoglycemic complications, and has a long life expectancy with no significant comorbidities may be encouraged to achieve an HbA1c of less than 6.5%.
Conversely, a patient with longstanding disease, at high risk of hypoglycemic complications, with a short life span, and having established vascular complications should have a goal of 7.5%-8.0%, or even higher. The guidelines discourage using the percentage of patients with an HbA1c of less than 7% as a quality indicator, because it undermines individualization of treatment goals.
Therapeutic Options
Lifestyle intervention forms the foundation of treatment for all patients with type 2 diabetes. Weight loss, or at least weight maintenance, should be encouraged through dietary, medical, or surgical means. Weight loss of 5%-10% can contribute to glycemic control. The physical activity goal is at least 150 minutes of moderate activity per week, or as much as possible – noting that any increase in activity level is beneficial.
Metformin is recommended as the usual first-line medical therapy for diabetes. It decreases hepatic gluconeogenesis, is generally weight neutral, and has a low risk of hypoglycemia. Sulfonylureas stimulate insulin release from the pancreas and carry a risk of weight gain and hypoglycemia. The meglinitides, also secretagogues, have less risk of hypoglycemia. Thiazolidinediones (TZDs) improve insulin sensitivity in muscle tissue and decrease hepatic gluconeogenesis. Side effects include weight gain, edema and heart failure, increased risk of bone fractures, and a possible increased risk of bladder cancer.
The injectable GLP-1 (glucagon-like peptide 1) receptor agonists increase insulin and decrease glucagon secretion, slow gastric emptying, and decrease appetite. They stimulate weight loss but also can cause nausea and vomiting. The DPP-4 (dipeptidyl peptidase 4) inhibitors decrease breakdown of GLP-1 and similarly lead to increased insulin and decreased glucagon secretion. Insulin, having many forms and regimens, becomes an option for patients with more severe disease; but it carries the risk of hypoglycemia and weight gain.
Implementation
Newly diagnosed patients near their HbA1c goal who are highly motivated can be offered a 3- to 6-month period of lifestyle-only intervention before starting pharmacologic therapy. Lifestyle intervention will not be enough for most patients to achieve target HbA1c goals, however, and oral, noninsulin injectable therapies and insulin therapies should then be added.
Initial drug monotherapy with metformin is appropriate for most patients. If target goals have not been reached after 3 months of titrating up from a low dose, then a second agent from a different class should be added, followed after another 3 months by a third agent.
Because of a relative lack of comparative long-term data about other oral and noninsulin injectable therapies, the next agent to be added will be determined based on the characteristics of a given class of medication, along with how those characteristics match a patient’s needs.
To help choose an individualized regimen, the guidelines outline five factors for each of the other drug categories: efficacy, risk of hypoglycemia, weight change, major side effects, and cost.
For example, sulfonylureas have high efficacy, a moderate risk of hypoglycemia, and low cost, while the TZDs have high efficacy, side effects of heart failure and edema, and high cost.
Adding a second agent will decrease HbA1c an average of 1%. If a medication has been added as a second- or third-line agent, and there has been no noticeable decrease in glycemic measures after 3 months, the patient should be considered a nonresponder. A drug from a different class should then be substituted.
If a patient has a high initial HbA1c (9.0%-10%), dual drug therapy may be appropriate from the start. If hyperglycemia is severe (fasting plasma glucose is greater than 300 mg/dL or HbA1c is greater than 10%), strong consideration should be given to starting therapy with insulin.
Transitioning to insulin often will be required, as progressive beta-cell destruction is a hallmark of the disease. The simplest approach is adding once-daily basal insulin, with patients taught to uptitrate their own insulin in a small incremental manner once or twice weekly based on the results of their daily fasting blood glucose values.
