Navigating Recent Clinical Trial Results: Cardiovascular Risk Reduction in a Patient with Clinical ASCVD and Diabetes-Associated Microvascular Complications
Medications:
alendronate 70 mg PO weekly
aspirin 81 mg PO daily
atorvastatin 40 mg po daily
chlorthalidone 25 mg PO daily
insulin glargine 20 units daily
lisinopril 40 mg PO daily
metformin 1000 mg PO twice daily
sulfamethoxazole/trimethoprim 400 mg-80 mg PO three times per week
Vitals: BP: 130/80 mm Hg, P: 68 beats per minute, BMI 31.1 kg/m2
Labs: eGFR 50 mL/min/1.73m2, liver function normal, A1C: 8.5%
The patient states adherence with appropriate lifestyle habits.
During the clinician-patient discussion at today's visit, you express concern about the patient's high atherosclerotic cardiovascular disease risk. The patient states she is willing to take additional medications to lower her risk.
Which ONE of the following medications will be the safest addition to the patient's current regimen to reduce her cardiovascular risk and blood glucose?
Show Answer
The correct answer is: B. Liraglutide.
Option B, liraglutide, is the safest option for this patient. In LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results), liraglutide was associated with ~20% reduction in the risk of poor renal outcomes regardless of baseline eGFR and 26% reduction in persistent macroalbuminuria. Liraglutide was not associated with retinopathy. There are other things to consider when prescribing liraglutide. The risk of hypoglycemia increases when an insulin secretagogue (e.g., sulfonylurea) or insulin is given with liraglutide, so it may be necessary to reduce the dose of insulin glargine for this patient before initiating liraglutide. In addition, the patient will likely lose weight with liraglutide use.
Option A, canagliflozin, is not the best option for this patient for several reasons. The most common adverse reactions reported with canagliflozin were UTIs, increased urination, and female genital mycotic infections. This patient has a past medical history of frequent UTIs and takes sulfamethaxazole/trimethoprim for UTI prophylaxis. In addition, canagliflozin use has been associated with increased fracture risk, and this patient has osteoporosis that may increase her risk for fractures. There are other things to consider when prescribing canagliflozin. The risk of hypoglycemia increases when an insulin secretagogue (e.g., sulfonylurea) or insulin is given with canagliflozin, so it may be necessary to reduce the dose of insulin glargine for this patient before initiating canagliflozin. Canagliflozin may reduce blood pressure, so it will be important to monitor for signs and symptoms of hypotension if canagliflozin is used for this patient. The patient may lose weight with the use of canagliflozin.
Option C, pioglitazone, is not the best option for this patient for several reasons. Pioglitazone use has been associated with increased fracture risk in women (5.1% pioglitazone vs. 3.2% placebo), and this patient has osteoporosis that may increase her risk for fractures. Pioglitazone use has been associated with fluid retention that may exacerbate or lead to congestive heart failure. The risk is increased patients with NYHA Class I and II heart failure who are taking insulin and pioglitazone. In addition, the risk of hypoglycemia increases when an insulin secretagogue (e.g., sulfonylurea) or insulin is given with pioglitazone, so it may be necessary to reduce the dose of insulin glargine for this patient before initiating pioglitazone. The patient may gain weight with pioglitazone.
Option D, semaglutide, is not the best option for this patient. In SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes), in patients who already had retinopathy, semaglutide was associated with an increased risk of severe retinal complications, including vitreous hemorrhage, diabetes-related blindness, and the need for an intravitreal medication or photocoagulation (HR 1.76, 95% CI 1.11-2.78; p = 0.02). Patients who have a history of diabetic retinopathy should be monitored for diabetic retinopathy progression. Semaglutide was associated with 36% reduction in the risk of persistent macroalbuminuria, persistent doubling of the SCr accompanied by an eGFR of less than or equal to 45 mL/min/1.73 m2, or the need for continuous renal-replacement therapy. The patient may lose weight with semaglutide.
U.S. Food & Drug Administration. FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin to include updates on bone fracture risk and new information on decreased bone mineral density. https://www.fda.gov/Drugs/DrugSafety/ucm461449.htm.
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