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(Table). The now vast arsenal of available medications for treating diabetes has made finding a universal treatment plan virtually impossible. Additionally, new drug classes mean new potential adverse effects that have not been investigated thoroughly because of the limited number of long-term studies. Potential adverse effects must be carefully considered before beginning treatment because type 2 diabetes is often accompanied by one or more comorbidities.

Experts contend that there is not now nor ever will be an ideal treatment plan for type 2 diabetes. The ADA suggests that a patient-centered approach will likely yield the most favorable outcomes. Involving patients in developing their treatment plans and carefully considering each person’s medical and lifestyle constraints can increase compliance and subsequently the overall effectiveness of diabetes treatment.

Given the abundance of available noninsulin diabetes medication and the recent shift from an algorithmic to a patient-centered approach, registered dietitian nutritionists (RDNs) will begin seeing modifications in both the types and combinations of drugs being used to treat type 2 diabetes. It is important to note that no single diabetes drug class is superior to another. Each new drug class moves clinicians closer to the goal of providing customized

treatment of type 2 diabetes. Becoming as well-versed in pharmacologic treatment as they are in the nutritional approach to diabetes not only will increase the credibility of RDNs, but it can strengthen their role within the health care team. Using the nutrition care process can equip RDNs with important tools for implementation of the patient-centered approach. They can obtain important information to assist the health care team in developing individualized type 2 diabetes treatment plans.

References:1. Centers for Disease Control and

Prevention. Distribution of first-listed diagnoses among hospital discharges with diabetes as any listed diagnosis, adults aged 18 years and older, United States, 2010. Diabetes Public Health Resource. 2014. http://www.cdc.gov/diabetes/statistics/hosp/adulttable1.htm. Accessed December2014.

2. Inzucchi SE, Bergenstal RM, Buse JB, et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364–1379.

According to the latest data from the National Hospital Discharge Survey, diabetes is the second most common diagnosis among hospital discharges in America (1). This fact not only highlights the grim epidemiologic characteristics of diabetes, but it is a clear indication that the disease is not being effectively managed.

Historically, in an effort to create a standardized treatment approach, type 2 diabetes was treated using a pharmacologic algorithm. With the exception of diet and lifestyle modification being the first step in defense against the disease and metformin being the second line of defense, the algorithmic approach proved ineffective due to the individualized nature of diabetes. A position statement published by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) in 2012 suggested that “Glycemic management in type 2 diabetes mellitus has become increasingly complex and, to some extent, controversial, with a widening array of pharmacological agents now available, mounting concerns about their potential adverse effects and new uncertainties regarding the benefits of intensive glycemic control on macrovascular complications” (2).

Since the introduction of sulfonylureas 60 years ago, many pharmaceutical companies have focused on the development of noninsulin diabetes medications

An Update on Noninsulin Treatment for Type 2 Diabetes

Joline Parer, dietetic studentHarvey, IL

11

Sulfonylureas (United Stated Food and Drug Administration Approval – 1955): glimepiride, glyburide, glipizide

• Mechanism of Action: stimulates beta cells in the pancreas to produce more insulin (long-acting)

• Dosing: once or twice daily with meals• Adverse effects: hypoglycemia, weight gain• May not be suitable for: people at high risk for

hypoglycemia

Meglinitides (1997): repaglinide, nateglinide• Mechanism of Action: stimulates beta cells in the

pancreas to produce more insulin (short-acting)• Dosing: with every meal• Adverse effects: hypoglycemia, weight gain• May not be suitable for: people at high risk for

hypoglycemia

Bigaunides (1994): metformin• Mechanism of Action: decreases glucose production

in the liver• Dosing: once or twice daily with meals OR at bedtime• Adverse effects: gastrointestinal distress (may be

less when taken with meals)• May not be suitable for: people with liver disease

Thiazolidinediones (1997): rosiglitazone, pioglitazone• Mechanism of Action: increases insulin sensitivity in

muscle and fat cells (effects on blood glucose may take 4-6 weeks or more)

• Dosing: once daily • Adverse effects: fluid retention• May not be suitable for: people with heart disease

Alpha-glucosidase Inhibitors (1995): acarbose, miglitol• Mechanism of Action: slows digestion of

carbohydrates by inhibiting alpha-glucosidases in the small intestine, lowers blood glucose concentrations following carbohydrate consumption

• Dosing: with first bite of every meal • Adverse effects: gastrointestinal distress• May not be suitable for: people with gastrointestinal

dysfunction

Glucagon-like peptide-1 (GLP-1) Receptor Agonists (2005): exenatide, exenatide XR, liraglutide, albiglutide, dulaglutide

GLP-1 is an incretin hormone that is released during meals from endocrine cells in the gut. It is responsible for stimulating glucose-induced insulin secretion, suppressing glucagon secretion, inhibiting gastric emptying, and reducing appetite and food intake. Levels of GLP-1 are enzymatically inactivated and reduced to fasting levels by the dipeptidyl peptidase-4 (DPP-4) enzyme. Only 10% to 20% of the GLP-1 hormone that enters the bloodstream is biologically active due to the activity of DPP-4 (4).

• Mechanism of Action: mimics the actions of GLP-1 for an extended period of time (due to resistance to DPP-4)

• Dosing: injected twice daily (exenatide), once daily (liraglutide), or once weekly (exenatide XR, albiglutide, dulaglutide)

• Adverse effects: mild gastrointestinal distress• May not be suitable for: people with gastrointestinal

dysfunction

DPP-4 inhibitors (2006): sitagliptin, saxagliptin, linagliptin, alogliptin

• Mechanism of Action: inhibits the DPP-4 enzyme, allowing the GLP-1 hormone to remain active for an extended period of time

• Dosing: once daily• Adverse effects: no notable adverse effects• May not be suitable for: people with renal

dysfunction

Sodium-glucose cotransporter 2 (SGLT-2) Inhibitors (2013): canagliflozin, dapagliflozin, empagliflozin

• Mechanism of Action: inhibits SGLT-2 (which is responsible for 90% of glucose reabsorption by the kidneys), causing excess glucose to be excreted through urine

• Dosing: once daily• Adverse effects: vaginal yeast infections, urinary

tract infections, diuresis• May not be suitable for: people with renal

dysfunction

Table. Classes of Noninsulin Diabetes Medications (3)

3. Diseases and Conditions. Type 2 Diabetes. Compare Diabetes Medication. Rochester, MN: Mayo Clinic; 2014. http://www.mayo

clinic.org/diseases-conditions/type-2-diabetes/in-depth/diabetes-treatment/art-20051004?pg=2. Accessed December 2014.

4. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368: 1696–1705.