When can semaglutide (glucagon-like peptide-1 receptor agonist) be stopped in a patient with type 2 diabetes mellitus (T2DM) who is on metformin and has a hemoglobin A1c (HbA1c) level of 7.0%?

When Can Semaglutide Be Stopped in T2DM Patients

Consider stopping or deintensifying semaglutide when HbA1c falls below 6.5% in this patient already on metformin with an HbA1c of 7.0%. 1

Primary Recommendation Based on Current HbA1c

Since your patient has achieved an HbA1c of 7.0% on metformin plus semaglutide, this falls within the optimal target range of 7-8% recommended for most adults with type 2 diabetes. 1, 2 At this HbA1c level, you should maintain current therapy rather than stopping semaglutide. 1

Specific Thresholds for Stopping Semaglutide

When HbA1c Falls Below 6.5%

The American College of Physicians explicitly recommends deintensifying pharmacologic therapy when HbA1c levels fall below 6.5%. 1 This guidance is based on:

• No trials demonstrate clinical outcome benefits from targeting HbA1c below 6.5% 1
• The ACCORD trial targeting HbA1c <6.5% (achieved 6.4%) was stopped early due to increased mortality and cardiovascular deaths 1
• Treatment below this threshold increases hypoglycemia risk, patient burden, and costs without proven benefit 1

Deintensification Strategy

When HbA1c drops below 6.5%, you should: 1

• Reduce the dosage of semaglutide (e.g., from 14 mg to 7 mg oral, or from 1.0 mg to 0.5 mg subcutaneous)
• Discontinue semaglutide entirely while continuing metformin alone
• Monitor HbA1c every 3 months after deintensification to ensure levels remain in the 7-8% target range 1

Important Caveat About Metformin

While deintensification applies to most glucose-lowering agents at HbA1c <6.5%, metformin occupies a special position. 1 The guidelines note that metformin:

• Does not cause hypoglycemia 1
• Is generally well-tolerated and low-cost 1
• Can be continued even at lower HbA1c levels, though the benefit-harm balance becomes uncertain below 7% 1

Therefore, if HbA1c falls below 6.5%, stop semaglutide first while maintaining metformin. 1

Clinical Scenarios Where Earlier Discontinuation Is Appropriate

Life Expectancy Less Than 10 Years

Stop targeting specific HbA1c levels and discontinue semaglutide if the patient has: 1, 2

• Advanced age (≥80 years) 1
• Residence in a nursing home 1
• Severe chronic conditions (dementia, cancer, end-stage kidney disease, severe COPD or CHF) 1
• Multiple comorbidities limiting life expectancy 2

In these populations, focus on minimizing hyperglycemic symptoms rather than achieving numerical targets, as treatment harms outweigh benefits. 1

Achievement of Remission Through Lifestyle

If the patient achieves HbA1c <7% through diet, exercise, and weight loss alone, discontinue all pharmacologic therapy including semaglutide. 1 The guidelines explicitly state that lower treatment targets are appropriate if achievable with lifestyle modifications without medication. 1

When to Continue Semaglutide Despite Good Control

Cardiovascular or Renal Indications

Do NOT stop semaglutide in patients with: 1

• Established atherosclerotic cardiovascular disease (ASCVD) 1
• Heart failure 1
• Chronic kidney disease 1
• High ASCVD risk (age ≥55 with significant arterial stenosis or left ventricular hypertrophy) 1

In these populations, semaglutide provides cardiovascular and renal benefits independent of glycemic control, and should be continued regardless of HbA1c level. 1 This represents a critical exception to the deintensification rule.

Monitoring Strategy After Stopping Semaglutide

After discontinuing semaglutide: 1

• Check HbA1c every 3 months to detect glycemic deterioration 1
• Reinitiate therapy if HbA1c rises to ≥7.5% on metformin monotherapy 2
• Counsel on lifestyle interventions including exercise, dietary changes, and weight maintenance 1

Common Pitfalls to Avoid

Do not pursue HbA1c <6.5% in patients with established cardiovascular disease, as this increases mortality risk. 2 The ACCORD trial definitively demonstrated harm from intensive glycemic control in this population. 1

Do not stop semaglutide solely based on duration of therapy. The decision should be driven by HbA1c levels, comorbidities, and cardiovascular/renal indications, not by arbitrary time limits. 1, 2

Do not deintensify therapy in younger patients (<55 years) with recent-onset diabetes, no complications, and long life expectancy (>15 years), even if HbA1c reaches 6.5-7.0%. 1, 2 These patients may benefit from maintaining tighter control to prevent long-term complications. 1