What medications should be considered as adjunct therapy for a patient with hypertension (HTN) on Lisinopril, diabetes mellitus (DM) on Metformin, hyperlipidemia (HLD) on statin, with a body mass index (BMI) of 35 and elevated hemoglobin A1C (HbA1C) levels?

Adjunct Medication Recommendations for Patient with HTN, DM, HLD, Eczema, and Elevated A1C

For a patient with hypertension on Lisinopril, diabetes on metformin, hyperlipidemia on statin, eczema using topical steroids, BMI 35, and elevated A1C levels, an SGLT2 inhibitor should be added as the preferred adjunct therapy. 1, 2

Primary Recommendation: SGLT2 Inhibitor

• SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are recommended as first-line adjunct therapy for patients with T2DM who have not achieved glycemic targets on metformin alone 1, 2
• SGLT2 inhibitors reduce risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization for heart failure 2
• For patients with elevated BMI (35 in this case), SGLT2 inhibitors provide additional benefit through weight reduction 3
• The combination of metformin with SGLT2 inhibitors has demonstrated superior efficacy in HbA1c and body weight reduction compared to metformin monotherapy 3

Alternative Option: GLP-1 Receptor Agonist

• If SGLT2 inhibitors are not tolerated or contraindicated, GLP-1 receptor agonists (liraglutide, semaglutide, or dulaglutide) should be considered 1
• GLP-1 RAs reduce risk for all-cause mortality, major adverse cardiovascular events, and stroke 2
• GLP-1 RAs may be particularly beneficial for patients who are overweight or obese (BMI 35 in this case) 1
• Semaglutide has demonstrated significant reductions in HbA1c and body weight when added to existing therapy 4

Clinical Decision Algorithm

1. First choice: SGLT2 inhibitor (empagliflozin preferred)

   • Benefits: Cardiovascular protection, renal protection, weight loss, low hypoglycemia risk 1, 5
   • Monitor: Renal function, genital mycotic infections, risk of diabetic ketoacidosis 6

2. Second choice: GLP-1 receptor agonist (if SGLT2 inhibitor not tolerated)

   • Benefits: Significant weight loss, cardiovascular protection, low hypoglycemia risk 1, 4
   • Consider: Injectable administration (except oral semaglutide), gastrointestinal side effects 7

3. Consider combination of both if single agent inadequate after 3 months

   • The combination of SGLT2 inhibitor and GLP-1 RA may have synergistic effects on glucose reduction, weight reduction, and cardiovascular risk reduction 8, 7

Hypertension Management Considerations

• Current regimen with Lisinopril (ACE inhibitor) is appropriate as RAS blockers are recommended first-line in patients with diabetes and hypertension 1
• If blood pressure remains uncontrolled, consider adding a calcium channel blocker as recommended combination therapy 1
• SGLT2 inhibitors provide modest additional blood pressure lowering effects, which would be beneficial for this patient 1

Special Considerations

• For this patient with BMI 35, medications that promote weight loss (SGLT2 inhibitors or GLP-1 RAs) are particularly advantageous 1, 2
• The patient's eczema requiring topical steroids is not a contraindication to either SGLT2 inhibitors or GLP-1 RAs 9
• Avoid thiazolidinediones as they can cause fluid retention and weight gain, which would be detrimental for this patient with elevated BMI 2
• DPP-4 inhibitors are not recommended as they have neutral effects on weight and lack cardiovascular benefits 2

Monitoring Recommendations

• Reassess HbA1c after 3 months of therapy 2
• Monitor renal function when using SGLT2 inhibitors (dose adjustments required with eGFR <60 mL/min/1.73m²) 2
• Evaluate for genital mycotic infections with SGLT2 inhibitors 5
• If using GLP-1 RA, monitor for gastrointestinal side effects which typically improve over time 4