What is the best add-on treatment for a 71-year-old male with type 2 diabetes mellitus (T2DM) on Jardiance (empagliflozin) 25 mg daily and metformin 1000 mg twice daily with a hemoglobin A1c (HbA1c) level of 7.4%?

GLP-1 Receptor Agonist is the Best Add-on Treatment for This Patient

For a 71-year-old male with type 2 diabetes on empagliflozin and metformin with an A1c of 7.4%, a GLP-1 receptor agonist is the best add-on treatment option due to its cardiovascular benefits, weight reduction effects, and low hypoglycemia risk.

Assessment of Current Therapy and Patient Factors

The patient is currently on:

• Empagliflozin (Jardiance) 25 mg daily - an SGLT2 inhibitor
• Metformin 1000 mg twice daily
• A1c is 7.4% (above target)
• Non-obese 71-year-old male

Rationale for GLP-1 Receptor Agonist as Add-on Therapy

Cardiovascular Benefits

• GLP-1 receptor agonists have proven cardiovascular benefits, which is particularly important for this older patient 1
• The ADA/EASD consensus report recommends GLP-1 RAs for patients with T2DM with A1c >7% 1
• The European Heart Journal guidelines recommend GLP-1 RAs with proven CV benefit in patients with T2DM and peripheral arterial disease 1

Complementary Mechanism of Action

• GLP-1 RAs work through a different mechanism than the patient's current medications:
  • Metformin: decreases hepatic glucose production
  • Empagliflozin: increases urinary glucose excretion
  • GLP-1 RA: increases glucose-dependent insulin secretion, decreases glucagon, slows gastric emptying 1

Weight Management

• GLP-1 RAs provide weight reduction benefits, which is advantageous even for non-obese patients 1, 2
• This complements the weight reduction effects already provided by empagliflozin

Low Hypoglycemia Risk

• The combination of metformin, SGLT2 inhibitor, and GLP-1 RA has a low risk of hypoglycemia 1, 2
• This is particularly important for an older patient (71 years) where hypoglycemia could have serious consequences

Alternative Options and Why They're Less Optimal

DPP-4 Inhibitors

• While DPP-4 inhibitors have a good safety profile, they provide less robust A1c reduction compared to GLP-1 RAs 1, 3
• DPP-4 inhibitors are weight neutral rather than weight-reducing 1
• DPP-4 inhibitors should not be used in combination with GLP-1 RAs as they work through related pathways 1

Sulfonylureas

• Associated with hypoglycemia risk and weight gain, making them less desirable for elderly patients 1
• Do not offer cardiovascular benefits like GLP-1 RAs 1

Thiazolidinediones

• Associated with weight gain, fluid retention, and increased risk of heart failure 1, 2
• Not ideal for elderly patients due to increased risk of fractures 1

Insulin

• Should be considered when A1c is significantly elevated (>10%) or when the patient is symptomatic 1
• This patient's A1c of 7.4% does not warrant insulin as the next step, especially given the hypoglycemia risk in an elderly patient

Implementation Considerations

1. Start with a lower dose of the selected GLP-1 RA and titrate up as tolerated
2. Monitor for gastrointestinal side effects (nausea, vomiting) which are common with GLP-1 RAs but typically transient
3. Reassess A1c after 3 months to evaluate efficacy
4. Consider once-weekly formulations for improved adherence if available

Potential Pitfalls to Avoid

• Failing to consider renal function when combining metformin with SGLT2 inhibitors and adding a GLP-1 RA
• Not educating the patient about potential gastrointestinal side effects of GLP-1 RAs, which could lead to discontinuation
• Overlooking the need to monitor for volume depletion with the combination of SGLT2 inhibitor and GLP-1 RA

In summary, a GLP-1 receptor agonist represents the optimal add-on therapy for this patient based on efficacy, cardiovascular benefits, weight effects, and safety profile, particularly considering the patient's age and current medication regimen.