What are the contraindications for weight loss medications in patients with a history of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM)?

Contraindications for Weight Loss Medications in Patients with CVD and T2DM

Sympathomimetic agents such as phentermine and phentermine/topiramate extended-release are contraindicated in patients with cardiovascular disease, including those with T2DM and CVD. 1, 2, 3

Specific Contraindications by Medication Class

Sympathomimetic Agents

• Phentermine and phentermine/topiramate ER:
  • Absolutely contraindicated in patients with history of cardiovascular disease 2
  • This includes coronary artery disease, stroke, arrhythmias, congestive heart failure, and uncontrolled hypertension 2
  • Should not be prescribed in patients with T2DM who have CVD 1

Thiazolidinediones

• Pioglitazone, rosiglitazone:
  • Contraindicated in patients with heart failure 1
  • Not recommended for weight loss in patients with T2DM and CVD due to risk of fluid retention and worsening heart failure 1

DPP-4 Inhibitors

• Saxagliptin:
  • Not recommended in patients with T2DM and high risk of heart failure 1
  • Other DPP-4 inhibitors may be used with caution

Safer Alternatives for Weight Management in CVD and T2DM

Preferred Options

1. GLP-1 Receptor Agonists (liraglutide, semaglutide, dulaglutide):

   • Recommended for patients with T2DM and CVD 1, 4
   • Demonstrated cardiovascular benefits in reducing CV events 1
   • Liraglutide specifically recommended to reduce risk of death in T2DM patients with CVD 1, 4
   • Provide significant weight loss (5-15% of body weight) 5

2. SGLT2 Inhibitors (empagliflozin, canagliflozin, dapagliflozin):

   • Recommended for patients with T2DM and CVD 1
   • Reduce CV events and mortality 1, 4
   • Empagliflozin specifically recommended to reduce risk of death in T2DM patients with CVD 1
   • Provide moderate weight loss (3-5% of body weight) 5

3. Orlistat:

   • Safe alternative for patients with CVD 1, 3
   • Works by inhibiting pancreatic lipase, reducing fat absorption 1
   • Not associated with adverse cardiovascular effects 3, 6
   • Modest weight loss effect (3-4% of body weight) 7

Clinical Decision Algorithm for Weight Loss Medication Selection

1. First, assess cardiovascular status:

   • If patient has established CVD (coronary artery disease, stroke, heart failure, arrhythmias):
     • Avoid all sympathomimetic agents (phentermine, phentermine/topiramate) 2
     • Avoid thiazolidinediones 1
     • Avoid saxagliptin 1

2. For patients with T2DM and CVD, prioritize medications with proven CV benefit:

   • GLP-1 RAs (liraglutide, semaglutide, dulaglutide) 1, 4
   • SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) 1, 4

3. If additional weight loss is needed:

   • Consider orlistat as an adjunct therapy 1, 3
   • Target weight loss of at least 5% to improve glycemic parameters 7

4. Monitor effectiveness:

   • Evaluate weight loss at 3 months 1
   • If <5% weight loss is achieved, consider discontinuing or changing medication 1
   • If ≥5% weight loss is achieved, continue therapy 1

Important Considerations and Caveats

• Weight loss medications should always be used as adjuncts to lifestyle modifications including diet, physical activity, and behavioral counseling 1
• Medication selection should consider effects on glycemic control, blood pressure, and lipid parameters 4
• Minimize medications for comorbid conditions that are associated with weight gain (certain antipsychotics, some antidepressants, glucocorticoids) 1
• For patients with T2DM, consider antidiabetic agents that promote weight loss rather than weight gain 1
• Long-term cardiovascular outcomes studies are still needed for many weight loss medications 6, 8
• Regular monitoring of cardiovascular parameters is essential when using any weight loss medication in patients with T2DM and CVD 4

By following these guidelines, clinicians can safely manage weight loss in patients with T2DM and CVD while minimizing cardiovascular risks and potentially improving cardiovascular outcomes.