Management of Obesity and Cardiovascular Risk

Medication Selection

• For patients with BMI >35 kg/m², GLP-1 RAs are the preferred second-line drug of choice due to their potential for weight loss, as recommended by the American Diabetes Association 1
• GLP-1 RAs are beneficial for reducing MACE, as recommended by the American College of Cardiology 2
• GLP-1 RAs provide superior weight loss compared to SGLT-2 inhibitors, according to the American College of Cardiology 1
• SGLT2 inhibitors, such as empagliflozin, canagliflozin, and dapagliflozin, are used in clinical practice for the treatment of type 2 diabetes, with their primary site of action being the proximal convoluted tubule in the kidneys, as noted by the American College of Cardiology 3

Dosage and Administration

• The American College of Cardiology recommends starting with the lowest dose and up-titrating slowly to the maximal tolerated dose 3
• For cardiovascular risk reduction, the goal dose for liraglutide is 1.8 mg daily, as recommended by the American College of Cardiology 3
• The recommended dose of canagliflozin is 100 mg orally once daily, with a maximum dose of 300 mg orally once daily, and for patients with renal impairment, the maximum dose is 100 mg daily for those with an eGFR of 30-59 ml/min/1.73 m², as recommended by the American College of Cardiology 2

Side Effects and Considerations

• GLP-1 RAs commonly cause nausea and vomiting initially, which may affect adherence, according to the American Diabetes Association 1
• GLP-1 RAs require subcutaneous injection, which some patients may find challenging, as noted by the American College of Cardiology 3
• Both medication classes can be expensive, and insurance coverage varies significantly, as noted by the American College of Cardiology 3
• SGLT2 inhibitors have an increased risk of lower-limb amputation, genital mycotic infections, and urinary tract infections, as warned by the Food and Drug Administration 4, 2
• Monitor for symptoms of ketoacidosis, consider reducing diuretic doses when initiating SGLT2 inhibitors in patients at risk for volume depletion, as recommended by the American Diabetes Association and National Kidney Foundation, with a moderate strength of evidence 5, 3, 6

Combination Therapy

• The American College of Cardiology suggests that while combination of SGLT-2 inhibitors and GLP-1 RAs may provide synergistic benefits, there are limited data on cardiovascular outcomes with this approach, and cost would likely be prohibitive 3
• The combination of GLP-1 receptor agonists and SGLT2 inhibitors may reduce major adverse cardiovascular events by 12-14%, as recommended by the American College of Cardiology, with a moderate strength of evidence 3

Cardiovascular Benefits

• Empagliflozin showed a 14% relative risk reduction in major adverse cardiovascular events (MACE) and a 38% reduction in cardiovascular death, indicating a strong class effect for SGLT2 inhibitors in reducing cardiovascular risk, as recommended by the American College of Cardiology 3
• SGLT2 inhibitors reduce the risk of cardiovascular death and hospitalization for heart failure by 26% in heart failure with reduced ejection fraction (HFrEF) and 18% in heart failure with preserved ejection fraction (HFpEF), with benefits seen regardless of diabetes status, according to the American Heart Association 7
• SGLT2 inhibitors can reduce hospitalization for heart failure by 26-35%, as noted by the American College of Cardiology 3
• Canagliflozin significantly reduced the composite outcome of cardiovascular death, MI, or stroke versus placebo (HR 0.86 [95% CI 0.75-0.97]) in the CANVAS Program, as noted by the American College of Cardiology 4

Renal Benefits

• SGLT2 inhibitors slow the progression of chronic kidney disease and reduce albuminuria, with benefits seen down to an eGFR of 30 mL/min/1.73 m², as suggested by the National Kidney Foundation 8
• Canagliflozin reduced the risk of the primary composite outcome (end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes) by 30% compared to placebo in patients with diabetic nephropathy, as noted by the American College of Cardiology 4

SGLT2 Inhibitor Comparison

Patient Selection

• SGLT2 inhibitors are recommended for patients with heart failure, providing benefits in reducing hospitalization for heart failure and cardiovascular death, with a moderate to high strength of evidence, as recommended by the American Diabetes Association and European Society of Cardiology 5
• Patients with type 2 diabetes and established cardiovascular disease or high CV risk, heart failure or CKD, are recommended to use SGLT2 inhibitors for cardiovascular benefit, regardless of baseline A1C, according to the American Diabetes Association and the American College of Physicians 9, 10
• Contraindications include severe renal impairment, end-stage renal disease or dialysis, and history of serious hypersensitivity reactions to the drug, as stated by the American College of Clinical Pharmacy 7