What is the next step in managing diabetes for patients not at goal on metformin (biguanide)?

Next Steps in Diabetes Management After Metformin

For patients not at glycemic goal on metformin, add a sodium-glucose cotransporter 2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1 RA) with demonstrated cardiovascular benefit, particularly in patients with established cardiovascular disease, kidney disease, or heart failure. 1

Patient Assessment and Decision Algorithm

When a patient on maximum tolerated metformin therapy is not meeting glycemic targets, follow this structured approach:

1. Evaluate current status:

   • Confirm adherence to maximum tolerated metformin dose (typically 2000 mg/day)
   • Check A1C level and determine how far from target
   • Assess for presence of:
     • Established atherosclerotic cardiovascular disease (ASCVD)
     • High ASCVD risk indicators
     • Chronic kidney disease (CKD)
     • Heart failure

2. Select appropriate add-on therapy based on comorbidities:

   • If patient has ASCVD, high ASCVD risk, CKD, or heart failure:

     • First choice: SGLT2 inhibitor with proven cardiovascular benefit
     • Alternative: GLP-1 RA with proven cardiovascular benefit
     • These recommendations apply regardless of A1C level 1

   • If patient has no cardiovascular/renal comorbidities:

     • Consider patient-specific factors:

       • Hypoglycemia risk
       • Impact on weight
       • Side effect profile
       • Cost
       • Route of administration
       • Patient preferences

     • Choose from: SGLT2 inhibitor, GLP-1 RA, DPP-4 inhibitor, thiazolidinedione, sulfonylurea, or basal insulin 1

Timing of Intensification

Treatment intensification should not be delayed when glycemic targets aren't met. The ADA recommends reassessing and adjusting therapy every 3-6 months 1. If monotherapy at maximum tolerated dose doesn't achieve or maintain A1C target after 3 months, promptly add a second agent 1.

Special Considerations

For patients with very high A1C:

• If A1C ≥9% but patient is not acutely symptomatic, consider initiating dual combination therapy 1
• If A1C ≥10% or blood glucose ≥300 mg/dL with symptoms (polyuria, polydipsia, weight loss), consider insulin-based therapy 1

For patients with cardiovascular disease:

• SGLT2 inhibitors and GLP-1 RAs have demonstrated cardiovascular risk reduction in clinical trials
• These agents should be prioritized even if A1C is at target 1

Practical Implementation Tips

• When adding a GLP-1 RA, start at the lowest dose and titrate up to minimize gastrointestinal side effects
• When adding an SGLT2 inhibitor, counsel patients about genital mycotic infections and urinary tract infections
• Continue metformin when adding other agents unless contraindicated 1
• Monitor for vitamin B12 deficiency in long-term metformin users, especially those with anemia or peripheral neuropathy 1, 2

Common Pitfalls to Avoid

1. Therapeutic inertia: Delaying intensification despite suboptimal glycemic control
2. Overlooking cardiovascular benefits: Failing to prioritize agents with proven cardiovascular benefit in appropriate patients
3. Discontinuing metformin: Metformin should generally be continued when adding other agents 1
4. Ignoring patient preferences: Not considering factors like injection aversion, cost concerns, or side effect profiles when selecting therapy

By following this evidence-based approach to treatment intensification after metformin, you can optimize both glycemic control and reduce long-term cardiovascular and renal complications in patients with type 2 diabetes.