In this section, you can review descriptions of medication classes that are currently available for the management of high blood glucose levels in the US, including information about mechanism of action, route of administration, and how current guidelines recommend each medication be introduced for treatment intensification in the progression of type 2 diabetes.
Patients with type 1 diabetes are treated with one basal insulin injection and 3-4 injections/day of prandial (mealtime) insulin or continuous subcutaneous insulin infusion (CSII).1 Mealtime insulin is matched to carbohydrate intake, premeal blood glucose, and anticipated physical activity.1 Patients at high risk of hypoglycemia should receive insulin analogs. Patients with frequent nocturnal hypoglycemia and/or hypoglycemia unawareness may benefit from a sensor-augmented low glucose threshold suspend pump for CSII.
More information about the various types of insulin can be found in the Insulin section.
In patients with type 2 diabetes, pharmacologic therapy is determined using a patient-centered approach and is combined with lifestyle changes necessary to achieve the overall diabetes management goals that have been defined. As the disease progresses, treatment is intensified using a guidelines-based algorithm (Figure 1).1 A downloadable version of this algorithm is available in the Guidelines Quick Reference.
Figure 1. Medications for type 2 diabetes. Adapted from American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2017;40(Suppl 1):S1-S135.
When lifestyle changes are unable to achieve or maintain glycemic goals, patients with type 2 diabetes typically receive biguanide monotherapy as their first pharmacologic treatment option unless there are contraindications or intolerance.1
Biguanides act on the AMP kinase pathway in the liver to lower glucose production.1 They are associated with gastrointestinal side effects and a risk of vitamin B12 deficiency, and there are multiple contraindications to their use, for example, in patients with chronic kidney disease (CKD) with an estimated glomerular filtration rate of <30 mL/min/1.73 m2.1
If the A1C target is not achieved after approximately 3 months of biguanide monotherapy, it can be combined with one of six treatment options to work towards achieving the established glycemic goals.1 These options include both oral and injection therapeutic options: Sulfonylureas, Thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, or Insulin.
The sulfonylureas act by closing potassium channels on pancreatic β-cell plasma membranes to stimulate insulin secretion.1 Sulfonylureas can cause hypoglycemia and weight gain.
These compounds work by activating the transcription factor PPARγ, which increases the sensitivity of the body’s tissues to insulin and improves glucose uptake.1 TZDs are associated with weight gain, edema, heart failure, and bone fractures, and rosiglitazone has been associated with increased LDL-C.
DPP-4 breaks down incretins (GLP-1 or GIP). GLP-1 is released after a meal and increases glucose-dependent insulin secretion, but is then quickly degraded. By inhibiting DPP-4 activity, these agents prolong the activity of GLP-1. Thus, DPP-4 inhibitors increase glucose-dependent insulin secretion and inhibit glucagon secretion. DPP-4 inhibitors have been associated with angioedema/urticaria and other immune-mediated dermatological side effects.1
The SGLT2 inhibitors act on the proximal nephron of the kidney to block glucose reabsorption, resulting in glycosuria (elimination of excess glucose via the urine).1 SGLT2 inhibitors have been associated with genitourinary infections, polyuria, volume depletion/hypotension/dizziness, increased LDL-C, and transient increases in creatinine.
There are several diabetes medications that are offered in combination. For information about other oral glucose-lowering agents, meglitinides, bile acid sequestrants, amylin mimetics, and dopamine-2 agonists, please refer to ADA recommendations.
By activating GLP-1 receptors, these agents increase glucose-dependent insulin secretion, decrease glucose-dependent glucagon secretion, slow gastric emptying, and increase feelings of satiety. GLP-1 receptor agonists have been associated with gastrointestinal side effects such as nausea, vomiting and diarrhea, and increased heart rate. Because GLP-1 receptor analogs are administered by injection, patient education and training is needed in order to ensure correct injection technique and dose adjustment.1
All human insulins or insulin analogs work by engaging insulin receptors to increase glucose uptake and decrease glucose secretion by the liver.1 Insulins are categorized based on how quickly they start to work, when the effect reaches its peak, and how long the effect lasts. Insulins are described as rapid-acting, short-acting, intermediate-acting, long-acting, and premixed.5
In patients with newly diagnosed type 2 diabetes and highly elevated blood glucose levels or A1C, consider initiating insulin therapy with or without additional agents.
Fast-acting insulins are used postprandially to control glucose from meals, whereas the long-acting insulins are used as basal insulins to control glucose levels throughout a 24-hour period.6 Depending on the type, insulin is administered by injection through a syringe, pen, pump, or inhalation.
Patients with type 2 diabetes who require insulin will start with basal insulin, which will need to be titrated to the correct dose.1 The most recent Standards of Medical Care in Diabetes guidelines include an algorithm for starting and adjusting insulin in patients with type 2 diabetes (Figure 2).1 It is important to have the insulin titrated appropriately in order to fully benefit from the insulin and thus help the patient reach the established glycemic goal.
Figure 2. Approach to starting and adjusting insulin in type 2 diabetes. Adapted from American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2017;40 (Suppl 1):S1-S135.
Basal insulin is usually added to oral agents, and usually one other noninsulin agent.1 If basal insulin has been titrated to the recommended fasting blood glucose range, but A1C remains above target, there are several options. These options include adding a GLP-1 receptor agonist or mealtime insulin, consisting of 1-3 injections of rapid-acting insulin analog administered at mealtime.1 When complex insulin regimens are used, noninsulin agents may be continued, although sulphonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists are typically stopped.
One of the key areas of concern when initiating insulin therapy is hypoglycemia. Insulin therapy is also associated with weight gain. Because insulin is administered as an injection and requires careful titration and administration in order to optimize glycemic control and minimize hypoglycemia, patient education and training is crucial.1
Tools for helping patients who are starting on insulin can be found here:
Diabetes management could be modified for patients in long-term care settings, due to patient factors such as age, comorbid conditions, polypharmacy, diminished functionality, and life expectancy.7 Glycemic goals for some older adults can be relaxed to avoid hypoglycemia.7 Hyperglycemia should also be avoided in all long-term care residents.7
Adapted from: Zettervall DK. In: Hass LB, Burke SD, eds. Diabetes Management in Long-Term Settings. Alexandria, VA: American Diabetes Association; 2014.
The healthcare provider should help minimize risk to the patient while attaining the recommended glycemic goals.7 As medications are reviewed upon a patient’s arrival and throughout the patient’s long-term stay, changes should be made accordingly if the patient is not meeting their glucose targets.7
If a patient is on <3 noninsulin medications, the Nurse Practitioner determines the target A1C value and chooses agents to provide appropriate A1C lowering based on the patient’s health status.7 When changing or adding medications, consider targeting different mechanisms of action.7 If the blood glucose targets are not met with ≤3 noninsulin medications, algorithms recommend initiating insulin therapy.7