Traditional type 2 diabetes medications often have untoward effects, such as gastrointestinal adverse reactions, weight gain, hypoglycemia, and cardiovascular risks, in addition to suboptimal glycemic control. Recently, researchers have discovered three new ways to interfere with metabolic pathways to improve glycemic control.

Incretins-gut hormones secreted in response to food ingestion that are partially responsible for the postprandial production of insulin-were found to have beneficial effects on blood glucose regulation, specifically glucagon-like peptide-1 (GLP-1). One hindrance encountered by researchers was that natural GLP-1 has a half-life of less than 2 minutes. This short half-life was addressed in two ways: 1) a synthetic GLP-1 agonist with a longer half-life was created and 2) a second substance was discovered that inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), which metabolizes GLP, thus extending its half-life.

A third new diabetes medication category, sodium-glucose cotransporter-2 (SGLT2) inhibitors, also shows promise for glycemic control. SGLT2 inhibitors reduce renal glucose reabsorption, which increases urinary glucose excretion.

Let's take a closer look at these three medications and what you need to know if your patients are taking them.

GLP-1 agonists

GLP-1 agonists are injectable medications with dosing schedules that correlate with their varying half-lives. Exenatide has a half-life of 2 to 4 hours and a twice-a-day dosing schedule. Sustained-release exenatide has once-weekly dosing. Liraglutide has a 13-hour half-life and is administered once a day.

Studies show significant reduction in hemoglobin A1C levels associated with the use of GLP-1 agonists. Postprandial fullness can promote weight loss with GLP-1 agonists because of delayed gastric emptying. Other clinical advantages of GLP-1 agonists may include decreased systolic BP, reduction of triglycerides, and low incidence of hypoglycemia because of glucose-dependent functioning. Adverse reactions include nausea, diarrhea, headaches, and dizziness.

DPP-4 inhibitors

DPP-4 inhibitors are administered orally once daily. There are several medications approved by the FDA, including sitagliptin-one of the original DPP-4 inhibitors-now marketed in combination form with metformin.

Advantages of DPP-4 inhibitors include increased insulin secretion with meals, weight neutrality, and decreased hypoglycemia. Weight neutrality with effective glycemic control is a major breakthrough for patients with type 2 diabetes. Until the advent of DPP-4 inhibitors, the most effective treatment was insulin, which is associated with weight gain. Adverse reactions of DPP-4 inhibitors include upper respiratory infections and headaches. Patients may also experience stomach discomfort and diarrhea.

Evaluation of GLP-1 agonists and DPP-4 inhibitors shows higher levels of glycemic control and hemoglobin A1C improvement with the use of GLP-1 agonists. Additionally, the weight loss associated with GLP-1 agonists is better than the weight neutrality of DPP-4 inhibitors. For these reasons, GLP-1 agonists are typically the first choice of treatment. However, both GLP-1 agonists and DPP-4 inhibitors are associated with an increased risk of pancreatitis.

SGLT2 inhibitors

Administered orally once a day, canagliflozin is the most popular SGLT2 inhibitor. This category of medication is associated with decreased weight, BP, and triglycerides, as well as improved hemoglobin A1C. Adverse reactions may include urinary tract infections, genital yeast infections, increased bone resorption, and increased low-density lipoprotein and high-density lipoprotein levels. Another possible adverse reaction of this medication category is ketosis. Symptoms associated with ketosis include difficulty breathing, nauseas, vomiting, abdominal pain, confusion, and fatigue.

Nursing implications

Patient teaching for GLP-1 agonists includes instruction on subcutaneous injection site locations and preparation, injection technique, and the importance of injection site rotation. A return demonstration of injection technique by the patient will confirm and reinforce his or her understanding. Redness, swelling, pain, and discharge at the injection site must promptly be reported to the healthcare provider. Compliance with dosing schedules is imperative for optimal results. Also educate patients about possible adverse reactions, such as headaches, dizziness, diarrhea, and transient nausea. Dosing schedule compliance may minimize adverse reactions.

For patients taking DPP-4 inhibitors, explain adverse reactions, such as upper respiratory infections (stuffy, runny nose and sore throat), headache, stomach discomfort, and diarrhea. Over-the-counter remedies may be used, but only after discussion with the healthcare provider. Also teach patients about the signs and symptoms of hypoglycemia if he or she is concurrently taking a sulfonylurea.

Patient education for SGLT2 inhibitors includes informing the patient that he or she may have increased urination, which increases the risk of dehydration. Teach the patient the signs and symptoms of dehydration, such as dry mouth and thirst, dizziness, weakness, palpitations, confusion, sluggishness, and fainting. Encourage patients to increase fluid intake to prevent dehydration. Female patients taking SGLT-2 inhibitors are at increased risk for mycotic vaginal infections; teach them to recognize signs and symptoms such as vulvar and vaginal erythema and irritation, and unusual and/or malodorous discharge. If an infection is suspected, the patient may need to be treated with antifungals such as fluconazole.

For all of these medications, vital signs, blood glucose, lipids, hemoglobin A1C, and weight should be closely monitored. It's also essential to teach patients about blood glucose monitoring, diet, and exercise.

A+ patient education

The education of patients with diabetes is often a task assigned to nurses. We must be well versed on the benefits and risks associated with diabetes medications. With the current prevalence of GLP-1 agonists, DPP4 inhibitors, and SGLT-2 inhibitors, we need to have a comprehensive understanding of these medications to impart clear instructions to our patients.

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