What medication should be recommended for a 48-year-old woman with type 2 diabetes mellitus (T2DM), hypertension (HTN), and new-onset edema, currently taking lisinopril (angiotensin-converting enzyme inhibitor, ACEI), hydrochlorothiazide (diuretic), metoprolol (beta-blocker), insulin glargine (long-acting insulin), and metformin (biguanide), with normal cardiac function, impaired renal function (eGFR 51 mL/min/1.73 m2), and proteinuria (urine protein-to-creatinine ratio 1.2 mg/mg)?

From the Guidelines

Dapagliflozin is the most appropriate medication to recommend for this patient. This 48-year-old woman with long-standing type 2 diabetes, hypertension, and new-onset edema would benefit from adding dapagliflozin to her current regimen. Her laboratory values show poor glycemic control with an HbA1c of 7.9%, mild renal impairment with an elevated creatinine of 1.30 mg/dL and reduced eGFR of 51 mL/min/1.73 m², and significant proteinuria with a urine protein-to-creatinine ratio of 1.2 mg/mg. Dapagliflozin, an SGLT2 inhibitor, offers multiple benefits for this patient: it improves glycemic control, reduces proteinuria, and provides cardiovascular and renal protection, as supported by the KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease 1.

The medication has been shown to slow progression of diabetic kidney disease and reduce heart failure hospitalizations, which is relevant given her edema despite normal ejection fraction, as demonstrated in the DAPA-CKD study 1. Dapagliflozin would address her poor glycemic control while simultaneously providing organ protection that other antihyperglycemic agents like sitagliptin cannot offer. Additionally, unlike amlodipine which may worsen edema, dapagliflozin has a diuretic effect that could help alleviate her fluid retention. While losartan (an ARB) would provide some renal protection, she is already on lisinopril (an ACE inhibitor) which works through a similar mechanism, making dapagliflozin the superior choice for comprehensive management of her diabetes, kidney disease, and edema.

Key benefits of dapagliflozin in this patient include:

• Improved glycemic control
• Reduced proteinuria
• Cardiovascular and renal protection
• Diuretic effect to alleviate edema
• Slowing progression of diabetic kidney disease
• Reduction in heart failure hospitalizations, as supported by recent studies 1.

From the FDA Drug Label

Patients with Renal Impairment At steady-state (20 mg once daily dapagliflozin for 7 days), adult patients with type 2 diabetes with mild, moderate, or severe renal impairment (as determined by eGFR) had geometric mean systemic exposures of dapagliflozin that were 45%, 100%, and 200% higher, respectively, as compared to patients with type 2 diabetes mellitus with normal renal function

• The patient has an eGFR of 51, which indicates moderate renal impairment.
• According to the drug label, the systemic exposure of dapagliflozin is 100% higher in patients with moderate renal impairment.
• The drug label does not provide a clear recommendation for dose adjustment in patients with moderate renal impairment, but it does mention that higher systemic exposure of dapagliflozin in patients with type 2 diabetes mellitus with renal impairment did not result in a correspondingly higher 24-hour urinary glucose excretion.
• Considering the patient's renal impairment and the potential increased exposure to dapagliflozin, dapagliflozin (B) may not be the best option.
• However, the FDA label does not directly answer the question of which medication to recommend, and the information provided is not sufficient to make a conclusive decision. The FDA drug label does not answer the question.

From the Research

Patient Profile

• The patient is a 48-year-old woman with type 2 diabetes mellitus for 15 years and hypertension.
• She is currently taking lisinopril, hydrochlorothiazide, metoprolol, insulin glargine, and metformin.
• Her BMI is 35, and she has 1+ pitting edema bilaterally.
• Laboratory studies show a hemoglobin A1c of 7.9%, blood urea nitrogen of 20 mg/dL, serum creatinine of 1.30 mg/dL, and eGFR of 51 mL/min/1.73 m2.

Medication Recommendation

• Based on the patient's profile and laboratory results, dapagliflozin is a suitable medication option.
• Dapagliflozin has been shown to improve glycemic control, reduce body weight and blood pressure, and have cardioprotective and renoprotective effects 2, 3, 4, 5.
• The DAPA-CKD trial demonstrated that dapagliflozin reduced the risk of kidney failure and cardiovascular events in patients with chronic kidney disease 3, 6.
• The patient's eGFR of 51 mL/min/1.73 m2 and presence of proteinuria (urine protein-to-creatinine ratio of 1.2) suggest that she may benefit from dapagliflozin's renoprotective effects.

Potential Benefits

• Dapagliflozin may help improve the patient's glycemic control and reduce her risk of kidney failure and cardiovascular events.
• It may also help with weight reduction and blood pressure control.
• The medication has a low risk of hypoglycemia and can be used in combination with other glucose-lowering agents, including insulin.

Potential Risks

• Dapagliflozin may increase the risk of genital and urinary tract infections, as well as ketoacidosis.
• However, the benefits of dapagliflozin are expected to outweigh the potential risks in this patient.