Pharmacologic Agents Used to Treat Type 2 Diabetes

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Q: I have several patients with type 2 diabetes and they're all on different medications. What medications are used now to manage type 2 diabetes and how do they work?
There are currently 12 classes of glucose lowering agents available to treat type 2 diabetes. The American Diabetes Association (ADA) (2017) provides useful information in the ADA Standards of Medical Care in Diabetes—2017 that help clinicians understand the physiological actions, advantages, and disadvantages of each. It's important to remember that all medications should be used with lifestyle management considerations.
First-line therapy for newly diagnosed type 2 diabetes is often lifestyle modifications to improve health, along with metformin (a biguanide); however, this will be determined based on patient-specific factors such as current A1C results, symptoms, medication characteristics, and patient preference. Metformin works by decreasing hepatic glucose production, which means hypoglycemia is rare. Other benefits include a reduced risk of cardiovascular events, ability to use in patients with an estimated glomerular filtration rate as low as 30 mL/min/1.73 m2, and it is inexpensive. There are a few disadvantages to be aware of, for example, some patients experience gastrointestinal side effects, vitamin B12 deficiency, and rarely lactic acidosis (ADA, 2017).
For patients with an A1C between 9% and 10% or if target A1C is not achieved after 3 months on metformin alone, then combination therapy is often considered with one of the following available options: sulfonylurea, meglitinide, thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor, glucagon-like peptide 1 (GLP-1) receptor agonist, sodium-glucose co-transporter-2 (SGLT2) inhibitor, or basal insulin. Again, the drug of choice will be determined based on patient preference, disease, and drug characteristics. For example, sulfonylureas work by increasing insulin secretion; therefore, hypoglycemia is a risk. Also, any time you increase circulating insulin there is a risk for weight gain. The benefits of sulfonylureas include reduced microvascular risk and they are relatively inexpensive. For patients with sulfa allergies, meglitinides (which also increase insulin secretion) may be used. This class of medication also has a risk for hypoglycemia and weight gain, but reduces postprandial hyperglycemia and offers more dosing flexibility; however, it is more expensive (ADA, 2017).
Thiazolidinediones work primarily by increasing insulin sensitivity, rather than insulin secretion, so the risk for hypoglycemia is low. Another benefit is the lower cost, and for patients using pioglitazone, a reduction in triglycerides. The disadvantages of this medication include an increased risk for weight gain, heart failure, bone fractures, and for patients taking rosiglitazone, an increase in LDL-C levels (ADA, 2017).
DPP-4 inhibitors decrease glucagon secretion and increase insulin secretion, but both are dependent on the blood glucose level; therefore, hypoglycemia is rare. Disadvantages include angioedema/urticaria and other immune-mediated dermatological effects and a potential increase in heart failure. Plus, the cost for this medication is high (ADA, 2017).
GLP-1 receptor agonists also decrease glucagon secretion and increase insulin secretion, but like DPP-4 inhibitors, this response is glucose dependent so the risk for hypoglycemia is low. This medication also slows gastric emptying and increases satiety, which can help with weight loss. Other benefits include decreased postprandial hyperglycemia, a reduction in some cardiovascular risk factors, and for patients taking liraglutide, lower cardiovascular disease (CVD) event rates and mortality have been noted in patients with CVD. Disadvantages include gastrointestinal side effects, increased heart rate, and the potential for acute pancreatitis. Like insulin, this medication must be injected, so training requirements must be considered (ADA, 2017).
SGLT2 inhibitors block glucose reabsorption by the kidney, resulting in increased glucosuria. The benefits of this medication include weight loss, decreased blood pressure, and for patients taking empagliflozin, the potential for lower cardiovascular events and mortality in patients with CVD.

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