What medication management should be added for a 40-year-old patient with uncontrolled diabetes mellitus (DM), elevated urine albumin-to-creatinine ratio (ACR), and a hemoglobin A1c (HbA1c) of 15%, recently initiated on insulin therapy?

From the Guidelines

For this patient with uncontrolled diabetes and elevated urine albumin/creatinine ratio, an SGLT2 inhibitor should be added to their treatment regimen, in addition to the already initiated insulin therapy, to reduce the risk of cardiovascular and kidney events, as recommended by the 2020 KDIGO clinical practice guideline 1. The patient's severely elevated A1c of 15 and elevated urine albumin/creatinine ratio indicate a high risk of cardiovascular and kidney complications, and the addition of an SGLT2 inhibitor, such as canagliflozin, dapagliflozin, or empagliflozin, can help reduce this risk, as shown in several studies 1. Some key points to consider when adding an SGLT2 inhibitor to this patient's treatment regimen include:

• Monitoring for potential adverse effects, such as modest volume contraction, blood pressure reduction, and weight loss, as well as the risk of hypovolemia and low blood pressure, especially in patients at risk for hypovolemia due to concomitant diuretic use 1.
• The SGLT2 inhibitor should be initiated at the lowest dose tested in cardiovascular and renal outcomes trials, and no further dose titration is needed for cardiovascular or renal risk reduction, although dose increases may provide further glucose reduction benefits if indicated 1.
• The patient should be educated on the potential adverse effects of SGLT2 inhibitors and the importance of regular monitoring of kidney function, as well as the need to adjust the dose of the SGLT2 inhibitor based on the patient's eGFR, with a maximum dose of 100 mg daily for canagliflozin and 10 mg daily for dapagliflozin and empagliflozin, and consideration of discontinuation if the eGFR falls below 30 mL/min/1.73 m2 1.
• The addition of an SGLT2 inhibitor to the patient's treatment regimen should be based on the patient's individualized glycemic goals and the potential benefits and risks of the medication, as well as the patient's preferences and values, and should be done in conjunction with ongoing monitoring and adjustment of the patient's treatment plan as needed to achieve optimal glycemic control and minimize the risk of cardiovascular and kidney complications 1.

From the FDA Drug Label

JARDIANCE used in combination with insulin (with or without metformin and/or sulfonylurea) provided statistically significant reductions in HbA1c and FPG compared to placebo after both 18 and 78 weeks of treatment JARDIANCE 10 mg or 25 mg daily also resulted in statistically significantly greater percent body weight reduction compared to placebo A total of 563 patients with type 2 diabetes inadequately controlled on multiple daily injections (MDI) of insulin (total daily dose >60 IU), alone or in combination with metformin, participated in a double-blind, placebo-controlled study to evaluate the efficacy of JARDIANCE as add-on therapy to MDI insulin over 18 weeks JARDIANCE 10 mg or 25 mg daily used in combination with MDI insulin (with or without metformin) provided statistically significant reductions in HbA1c compared to placebo after 18 weeks of treatment

The patient has uncontrolled diabetes with an A1c of 15 and has just been started on insulin. Empagliflozin (JARDIANCE) can be added to the patient's medication management as it has been shown to provide statistically significant reductions in HbA1c when used in combination with insulin.

• The recommended dose is 10 mg or 25 mg daily.
• It is essential to monitor the patient's renal function, as empagliflozin may increase the risk of acute impairment in renal function.
• The patient should also be monitored for signs of hypotension, as empagliflozin may increase the risk of hypotension in patients at risk for volume contraction 2.

From the Research

Medication Management for Uncontrolled Diabetes with Elevated Urine Albumin/Creatinine Ratio

• The patient has uncontrolled diabetes with an A1c of 15 and an elevated urine albumin/creatinine ratio of 8 mmol/L, indicating kidney damage.
• According to the study 3, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are recommended as first-line antihypertensive therapy in patients with albuminuria (urine albumin/creatinine ratio ≥300 mg/g).
• The study 4 suggests that ARBs may be associated with fewer adverse events compared to ACE inhibitors, but the study 5 found that ACE inhibitors may be more effective in reducing the incidence of major adverse cardiac events, cardiac death, and all-cause death in hypertensive patients with acute myocardial infarction.
• Considering the patient's elevated urine albumin/creatinine ratio and uncontrolled diabetes, adding an ACE inhibitor to their medication regimen may be beneficial in reducing kidney damage and improving blood pressure control, as suggested by the study 6.
• The study 7 found that twice-daily dosing of ACE inhibitors may promote added blood pressure-lowering effects, but this should be determined on a case-by-case basis, taking into account the patient's individual needs and potential adherence issues.

Potential Medication Options

• ACE inhibitors, such as lisinopril or enalapril, may be considered as a first-line treatment for this patient, given their potential benefits in reducing kidney damage and improving blood pressure control 6, 3.
• ARBs, such as losartan or valsartan, may also be considered as an alternative to ACE inhibitors, but the study 5 suggests that ACE inhibitors may be more effective in reducing the incidence of major adverse cardiac events.