Hyperglycemia Management in Diabetic Patients

Key Points

Glycemic targets and treatments to lower glucose must be individualized according to specific patient characteristics. The mainstay of any type 2 diabetes treatment program is still diet, exercise, and education. Metformin is the preferred first-line drug, in the absence of contraindications. Data are limited regarding use of agents other than metformin. A reasonable approach is combination therapy with 1 to 2 additional oral or injectable agents, with the goal of minimizing side effects to the extent possible. To maintain glycemic control, many patients will ultimately need insulin monotherapy or in combination with other medications. Whenever possible, the patient should participate in all treatment decisions, focusing on their preferences, needs, and values. A major treatment goal must be comprehensive cardiovascular risk reduction.

Highlights

Current guidelines suggest that the goal HbA1c level should be less than 7%. This goal can be achieved with fasting glucose levels of less than 130 mg/dL and postprandial glucose levels of less than 180 mg/dL. More strict HbA1c targets may be considered among patients with long life expectancy and no history of cardiovascular disease. Although all patients with diabetes should receive instruction on a healthy lifestyle, this advice should be personalized to account for a patient's personal and cultural preferences. Advice on exercise should target a minimum of 150 minutes per week of activity that might include aerobic, resistance, and flexibility training. Metformin is the mainstay of oral therapy for type 2 diabetes because it effectively lowers serum glucose levels without raising body weight or the risk for hypoglycemia. It should be initiated at a low dose to reduce the incidence of gastrointestinal adverse effects. Patients with poor glycemic control at baseline, as characterized by an HbA1c level of 9% or more, may receive combination therapy at the outset of treatment. Insulin therapy should be considered as the initial therapy for patients with plasma glucose levels of more than 300 mg/dL or HbA1c levels greater than 10%. Adding a second agent is associated with an average additional reduction of HbA1c levels of 1%. The choice of a second agent should be based not only on improving HbA1c values but also on improving the treatment's adverse effect profile and cost. Patients with an HbA1c value exceeding 8.5% with 2-drug therapy should receive insulin as opposed to a third antidiabetic agent.

Insulin is usually started at a low dose of 0.1 to 0.2 unit/kg/day. It is reasonable to have patients slowly titrate up their insulin dose once or twice weekly if glycemic targets are not met. The addition of prandial to basal insulin is usually necessary when the dose of insulin climbs to 0.5 to 1 unit/kg/day. Insulin secretagogues such as sulfonylureas may be continued during treatment with basal insulin only but should be stopped when prandial insulin is prescribed. HbA1c targets up to 8% may be acceptable among older and frail patients with diabetes. Older adults are at higher risk for severe complications related to hypoglycemia, and this complication should be assiduously avoided among these patients. There are no sex-based differences in response to treatment with antidiabetic drugs. Although Latinos tend to have greater insulin resistance and persons of East Asian descent are more likely to have beta-cell dysfunction, these broad traits should not necessarily influence treatment decisions for the individual. Metformin may be used among patients with mild heart failure, and current practice standards regarding the use of metformin in the setting of chronic kidney disease are too restrictive. Metformin can be used until the estimated glomerular filtration rate decreases to 30 mL/minute or less. Some evidence exists that pioglitazone may be particularly advantageous for patients with mild steatohepatitis.

Clinical Implications

Strict glycemic control appears to reduce the risk for microvascular complications of diabetes, such as retinopathy and nephropathy, to a greater extent than reducing the risk for cardiovascular disease. The current position statement from the ADA/EASD endorses metformin as the initial therapy for most patients with type 2 diabetes. Metformin should be initiated at a low dose to avoid adverse effects and can be continued even in cases of moderate chronic kidney disease. Patients with an HbA1c value exceeding 8.5% with 2-drug therapy should receive insulin as opposed to a third antidiabetic agent.