What are the recommended newer antidiabetic medications, such as Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors or Glucagon-Like Peptide-1 (GLP-1) receptor agonists, for patients with type 2 diabetes?

Newer Antidiabetic Medications for Type 2 Diabetes

SGLT2 inhibitors and GLP-1 receptor agonists should be added to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control due to their proven benefits in reducing mortality and cardiovascular events. 1

First-Line Recommendations

The American College of Physicians (ACP) provides clear guidance on newer antidiabetic medications:

• Metformin remains the first-line medication (unless contraindicated) along with lifestyle modifications 1
• When additional therapy is needed, SGLT2 inhibitors or GLP-1 receptor agonists should be added 1
• DPP-4 inhibitors should NOT be added to reduce morbidity and mortality (strong recommendation with high-certainty evidence) 1

Benefits of SGLT2 Inhibitors

SGLT2 inhibitors (like empagliflozin) provide significant benefits:

• Reduce all-cause mortality (high certainty of evidence) 1
• Reduce major adverse cardiovascular events (MACE) (moderate to high certainty) 1
• Reduce progression of chronic kidney disease (high certainty) 1
• Reduce hospitalization due to heart failure (high certainty) 1
• Reduce serious adverse events and severe hypoglycemia compared to usual care 1
• FDA-approved indications include glycemic control and cardiovascular risk reduction 2

Benefits of GLP-1 Receptor Agonists

GLP-1 receptor agonists (like semaglutide) offer these advantages:

• Reduce all-cause mortality (high certainty of evidence) 1
• Reduce major adverse cardiovascular events (MACE) (moderate to high certainty) 1
• Specifically reduce stroke risk (high certainty) 1, 3
• Promote weight loss 1
• FDA-approved indications include glycemic control and reduction of major adverse cardiovascular events 4

Patient-Specific Medication Selection Algorithm

Based on the highest quality evidence, choose between these medication classes as follows:

1. Prioritize SGLT2 inhibitors when the patient has:

   • Heart failure, particularly with reduced ejection fraction 1
   • Chronic kidney disease 1
   • High risk for hospitalization due to heart failure 1

2. Prioritize GLP-1 receptor agonists when the patient has:

   • Increased risk for stroke 1, 3
   • Weight loss as an important treatment goal 1
   • Established atherosclerotic cardiovascular disease 1, 3

Important Clinical Considerations

• Both medication classes reduce severe hypoglycemia compared to sulfonylureas and insulin 1
• The European Society of Cardiology (ESC) recommends classifying patients according to cardiovascular risk levels to guide treatment decisions 1
• Consider these medications independent of baseline HbA1c when cardiovascular risk reduction is the primary goal 1, 3
• Target HbA1c levels between 7% and 8% in most adults with type 2 diabetes 1

Potential Pitfalls and Caveats

• SGLT2 inhibitors: Monitor for genitourinary infections, volume depletion, and diabetic ketoacidosis 2
• GLP-1 receptor agonists: Not studied in patients with history of pancreatitis 4
• Neither class is indicated for type 1 diabetes or diabetic ketoacidosis 4, 2
• Patients with foot ulcers or at high risk for amputation should only be treated with SGLT2 inhibitors after careful consideration of risks and benefits 1
• Consider reducing doses of insulin or sulfonylureas when adding these medications to reduce hypoglycemia risk 1

The evidence strongly supports adding either an SGLT2 inhibitor or GLP-1 receptor agonist to metformin therapy in patients with type 2 diabetes requiring additional glycemic control, with specific selection guided by the patient's comorbidities and cardiovascular risk profile.