Managing Patients With Type 2 Diabetes Poses Challenges

Balancing treatment options and medication safety can be challenging when managing patients with type 2 diabetes (T2D). T2D is considered a major cardiovascular (CV) risk factor, and the updated American Diabetes Association (ADA) guidelines reflect the need to focus on CV risk reduction.¹ Awareness of comorbidities, including established CV diseases, hypertension, and obesity, should help with selecting the best therapeutic agents to improve CV outcomes, and pharmacists can play an important role in this process.² There are also recent safety updates for some antihyperglycemic medications.

Guideline Updates and Pharmacotherapy

Recent CV outcomes trial data demonstrate that individuals with atherosclerotic CV disease should begin with lifestyle modifications and metformin.¹ Pharmacists should continue to recommend exercise for at least 150 minutes per week and smoking cessation. The ADA recommends the following glycemic goals for nonpregnant adults with diabetes: glycated hemoglobin (A1C), <7%; fasting plasma glucose, 80 to 130 mg/dL; and postprandial glucose, <180 mg/dL.¹ There are differences regarding A1C goals among the ADA, the American College of Physicians (ACP), and the American Association of Clinical Endocrinologists (see Figure).^1,3,4 The ACP recommends a target A1C between 7% and 8%, which has sparked controversy with the ADA.^4,5 The ADA recommends reserving less stringent A1C goals for patients with advanced microvascular or macrovascular complications, extensive comorbid conditions, a history of severe hypoglycemia, limited life expectancy, or long-standing diabetes in which the goal is difficult to achieve.¹ Ultimately, it is always important to individualize therapy for patients to help them achieve the best outcomes.

Encourage patients to perform self-monitoring of blood glucose (SMBG) to ensure appropriate pharmacotherapy and optimal T2D management.¹ Blood glucose meters record the values, making it easy for patients to take the readings to the pharmacy and physician appointments. Patients with intensive insulin therapies, such as multiple-dose insulin and insulin pumps, should perform SMBG after treating low blood glucose, at bedtime, before meals and snacks, occasionally 2 hours after eating, and prior to activities like driving and exercise.¹ There is less evidence regarding recommended frequency of blood glucose monitoring in patients on less intensive insulin regimens or oral medications.¹ However, frequent monitoring of fasting and after-meal blood glucose can help patients meet glycemic goals.

Metformin is still considered the initial drug of choice for treating T2D.^1,2 Lifestyle management and monotherapy with metformin are recommended for patients with an A1C of <9%.¹ Because long-term metformin use can cause vitamin B₁₂ deficiency, levels should be monitored periodically. If A1C is ≥9%, dual therapy should be considered.¹ There are 6 treatment options for combination therapy with metformin: basal insulin, a dipeptidyl-peptidase-4 inhibitor, a glucagon-like peptide-1 (GLP-1) receptor agonist, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a sulfonylurea, and a thiazolidinedione.¹ When A1C is ≥10% and blood glucose is at least 300 mg/dL, combination insulin injectable therapy should be used.¹

Randomized controlled trials have reported statistically significant reductions in CV events for 2 SGLT2 inhibitors, canagliflozin (Invokana) and empagliflozin (Jardiance), and 1 GLP-1 receptor agonist, liraglutide (Victoza).^6,7 The studies examined the combination of metformin with these medications. Additionally, there are continuing studies assessing whether other medications in these classes have the same beneficial CV effects.

Safety Updates for SGLT2 Inhibitors

There have recently been serious adverse effects associated with SGLT2 inhibitors, such as foot and leg amputations and genital infections.^8,9 Genital infections are a rare but serious complication that may cause a life-threatening bacterial infection known as Fournier gangrene.⁸ This information has been updated in the FDA’s Medication Guides.¹⁰ Pharmacists should advise patients to seek medical care immediately if they have symptoms, including a fever above 100.4°F, redness, swelling of the genitals and rectum, and tenderness.⁸ Additionally, the SGLT2 inhibitor should be discontinued in patients who develop these symptoms.

A boxed warning discussing the increased risk of foot and leg amputations was added to the prescribing information for canagliflozin.⁹ Risk factors include diabetic foot ulcers, neuropathy, peripheral vascular disease, and prior amputations.⁹ Pharmacists should monitor patients on canagliflozin for the following signs and symptoms: foot and leg infections, sores or ulcers, and tenderness.⁹ If these symptoms occur, canagliflozin should be discontinued. It is also important for pharmacists to report any adverse drug reactions associated with SGLT2 inhibitors to the FDA’s MedWatch program.

Jennifer Gershman, PharmD, CPh, is a drug information pharmacist and Pharmacy Times^® contributor who resides in south Florida.

References

• American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(suppl 1):S73-S85. doi: 10.2337/dc18-S008.
• Carbone S, Dixon DL, Buckley LF, Abbate A. Glucose-lowering therapies for cardiovascular risk reduction in type 2 diabetes mellitus: state-of-the-art review. Mayo Clin Proc. 2018;93(11):1629-1647. doi: 10.1016/j.mayocp.2018.07.018.
• Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2018 executive summary. Endocr Pract. 2018;24(1):91-120. doi: 10.4158/CS-2017-0153.
• Qaseem A, Wilt TJ, Kansagara D, et al. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: a guidance statement update from the American College of Physicians. Ann Intern Med. 2018;168(8):569-576. doi: 10.7326/M17-0939.
• American Diabetes Association deeply concerned about new guidance from American College of Physicians regarding blood glucose targets for people with type 2 diabetes [news release]. Arlington, VA: American Diabetes Association; March 8, 2018. diabetes.org/newsroom/press-releases/2018/ada-acp-guidance-response.html. Accessed November 16, 2018.
• Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi: 10.1056/NEJMoa1504720.
• Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322. doi: 10.1056/NEJMoa1603827.
• SGLT2 (sodium-glucose cotransporter-2) inhibitors for diabetes: drug safety communication - regarding rare occurrences of a serious infection of the genital area. FDA website. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm618908.htm. Published August 29, 2018. Accessed November 15, 2018.
• FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). FDA website. fda.gov/Drugs/DrugSafety/ucm557507.htm. Updated July 2017. Accessed December 14, 2018.
• FDA. Medication guides. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=medguide.page&utm_campaign=FDA%20Launches%20New%20Medication%20Guide%20Database&utm_medium=email&utm_source=Eloqua. Accessed December 14, 2018.