Can I prescribe saxagliptin (ONGLYZA) for a 38-year-old patient with diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, and diabetic retinopathy?

Saxagliptin Use in a 38-Year-Old Patient with Diabetes, Hypertension, Hyperlipidemia, and Diabetic Retinopathy

Saxagliptin is not recommended for this 38-year-old patient with diabetes, hypertension, hyperlipidemia, and diabetic retinopathy due to increased risk of heart failure hospitalization and lack of cardiovascular benefit compared to alternative agents. Instead, SGLT2 inhibitors or GLP-1 receptor agonists should be prioritized as they offer superior cardiovascular and renal protection.

Rationale Against Saxagliptin Use

Cardiovascular Risk Concerns

• The 2023 European Society of Cardiology (ESC) guidelines specifically state that "saxagliptin is not recommended in patients with T2DM and a high risk of HF" 1
• The SAVOR-TIMI 53 trial demonstrated that saxagliptin was associated with a 27% increased risk of hospitalization for heart failure compared to placebo (3.5% vs. 2.8%, p=0.007) 2
• This patient has multiple cardiovascular risk factors (diabetes, hypertension, hyperlipidemia) that place them at elevated risk

Retinopathy Considerations

• The patient already has diabetic retinopathy, which requires aggressive management of all cardiovascular risk factors
• According to the 2023 Diabetes Care guidelines, optimizing glycemic control, blood pressure, and serum lipid control is key to reducing the risk or slowing the progression of diabetic retinopathy 1
• Saxagliptin does not offer any specific benefits for retinopathy management compared to other diabetes medications

Preferred Alternative Treatments

First-Line Recommendations

1. SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin):

   • Recommended by ESC guidelines to reduce CV events in patients with T2DM and CVD or at high CV risk 1
   • Specifically recommended to lower risk of heart failure hospitalization 1
   • Recommended to reduce progression of diabetic kidney disease 1

2. GLP-1 receptor agonists (liraglutide, semaglutide, or dulaglutide):

   • Recommended for patients with T2DM and CVD or at high CV risk to reduce CV events 1
   • Liraglutide specifically recommended to reduce risk of death in high-risk patients 1

Medication Selection Algorithm

1. First choice: SGLT2 inhibitor (empagliflozin, canagliflozin, or dapagliflozin)

   • Benefits: CV protection, heart failure risk reduction, renal protection
   • Check eGFR before initiating

2. Second choice/Add-on: GLP-1 receptor agonist (liraglutide, semaglutide, dulaglutide)

   • Benefits: CV protection, weight loss, A1C reduction
   • Consider if additional glycemic control needed or if SGLT2 inhibitor contraindicated

3. Base therapy: Continue metformin if already prescribed and tolerated

   • Benefits: Well-established efficacy, safety, and cost-effectiveness

Additional Management Considerations

Retinopathy Management

• Ensure regular comprehensive eye examinations by an ophthalmologist 1
• Optimize glycemic control to reduce risk or slow progression of diabetic retinopathy 1
• Optimize blood pressure and lipid control 1

Cardiovascular Risk Management

• Statin therapy is recommended for this patient (age 38 with diabetes and additional ASCVD risk factors) 1
• Consider high-intensity statin to reduce LDL cholesterol by ≥50% 1
• Optimize blood pressure control, preferably with RAAS blockers 1

Common Pitfalls to Avoid

1. Overlooking heart failure risk: DPP-4 inhibitors, particularly saxagliptin, have been associated with increased heart failure hospitalization risk
2. Focusing only on glucose control: This patient needs medications that address both glycemic control AND cardiovascular/renal protection
3. Ignoring retinopathy progression: Medication choices should consider overall vascular protection to prevent worsening of existing retinopathy
4. Delaying comprehensive management: This patient's multiple comorbidities require prompt, aggressive intervention for all risk factors

In conclusion, saxagliptin should be avoided in this patient due to increased heart failure risk and availability of superior alternatives. SGLT2 inhibitors or GLP-1 receptor agonists would be more appropriate choices given their proven cardiovascular benefits and the patient's risk profile.