JC, a 65-year old male was recently diagnosed with type 2 diabetes. His physician has determined he will need long term therapy and requested your expertise as the pharmacist to decide which medication would be most appropriate to initiate. JC’s laboratory findings and vitals from his appointment yesterday are listed below: 

Past medical history: 

Hypertension

End-stage renal disease (Hemodialysis Mon-Wed-Fri)

Labs/Vitals: 

Ht: 5’11 ft 

Wt: 220 lbs 

BP: 147/87 mmHg 

HR: 72 BPM 

Temp: 98.4 F 

Glucose: 160 mg/dL (70-130 mg/dL) 

HbA1C: 8.3% (<7%)

SCr: 2.4 mg/dL (0.5-1.2 mg/dL) 

Na: 141 mEq/L (135-145 mEq/L) 

Cl: 102 mEq/L (95-105 mEq/L) 

K: 4.9 mEq/L (3.5-5 mEq/L) 

Ca: 8.5 mg/dL (8.5-10.5 mg/dL) 

Mg: 2.1 mg/dL (1.7-2.2 mg/dL)         

He is clinically stable and has no acute management needs for his diabetes. What would be an appropriate initial therapy for JC’s practitioner to prescribe to improve his long-term glycemic control? 

A. Empagliflozin

B. Metformin

C. Dapagliflozin

D. Semaglutide

Answer with rationale: 

Diabetes mellitus is incredibly common, with an estimated 850 million cases worldwide per the World Health Organization. For many years, the initial therapy for type II diabetes, which represents nearly 85-90% of overall diabetes, has been metformin. Metformin offers low risk of hypoglycemia, is very affordable, does not cause weight gain, and overall is well tolerated as long as initial doses are low and slowly titrated to target goals in order to limit gastrointestinal side effects (primarily diarrhea).

In recent years, some Sodium-glucose Cotransporter-2 inhibitors (SGLT-2) as well as Glucagon-like peptide-1 (GLP-1) receptor agonists have become first-line agents along with metformin due to studies demonstrating improved long-term cardiovascular outcomes and therefore more initial options exist.

The key to this case is the patient's history: ESRD (dialysis dependent). Patients with ESRD are assumed to have a eGFR of < 10mL/min. When evaluating medication therapy for nearly every disease state including diabetes, a calculated creatinine clearance is critical to ensure drugs are dosed appropriately or in some circumstances may be contraindicated. 

Answer A is incorrect. Empagliflozin is an SGLT-2 inhibitor that is renally cleared and its efficacy is dependent on renal function. While SGLT-2 inhibitors offer cardiovascular and renal protective effects when used in the early stages of chronic kidney disease, their use would not be recommended in ESRD. Empagliflozin is not recommended in patients with an eGFR < 30 mL/min when managing blood sugar. 

Answer B is incorrect. Metformin use is contraindicated in ESRD (anyone with an estimated eGFR < 30mL/min) because it is eliminated by the kidneys and can accumulate if not properly cleared. Metformin also carries the life-threatening risk of lactic acidosis which while rare has an increased risk in severe kidney disease.

Answer C is incorrect. Similar to answer choice A, dapagliflozin is an SGLT-2 inhibitor that relies on renal function to be efficacious. The patient above has poor renal function and an SGLT-2 inhibitor would not be able to adequately clear glucose renally. Dapagliflozin is not recommended in patients with an eGFR < 45mL/min when managing blood sugar. 

Answer D is correct. Semaglutide is a GLP-1 receptor agonist that is effective for decreasing HbA1c and increasing weight loss. Semaglutide is an appropriate treatment option for this patient because its efficacy is independent from renal filtration. Semaglutide is not eliminated significantly via the kidneys and is a safe diabetes treatment option despite the patient’s ESRD.

Brand/generics Covered: 

Empagliflozin (Jardiance), Metformin (Glucophage), Dapagliflozin (Farxiga)

Naplex Competencies Covered: 

3. A. 2 - Appropriateness of therapy

3. D. 1 - Therapeutic goals

3. D. 3 - Effectiveness