Is an A1c level of 7.6 a concern for a 67-year-old man with Down syndrome on Xigduo (dapagliflozin and metformin) and Vascepa (icosapent ethyl)?

A1C of 7.6% in a 67-Year-Old Man with Down Syndrome

An A1C of 7.6% is acceptable and does not require intensification of therapy in this 67-year-old man with Down syndrome on Xigduo and Vascepa. In fact, this level may represent an appropriate individualized target given his complex health status, and further tightening of glycemic control could increase risks without meaningful benefit.

Rationale for This Recommendation

Current Glycemic Target Framework

The 2023 American Diabetes Association guidelines explicitly state that less stringent A1C goals (such as <8%) may be appropriate for patients with limited life expectancy or where the harms of treatment are greater than the benefits 1. For this patient:

• Down syndrome is associated with reduced life expectancy (typically 50-60 years, though improving), making him statistically beyond average life expectancy for his condition 1
• Complex health status warrants less aggressive targets to minimize hypoglycemia risk and treatment burden 1
• The current A1C of 7.6% falls well within the recommended <8% target for patients with complex/intermediate to very complex/poor health status 1

Evidence Supporting Less Stringent Control in Older Adults

Recent data from the Atherosclerosis Risk in Communities (ARIC) study demonstrated that older adults with very complex/poor health and A1C ≥8% had higher mortality risk (HR 1.76), but those with A1C <7% were not at elevated risk regardless of health status 2. Your patient's A1C of 7.6% sits in the safe middle ground, avoiding both the risks of overly tight control and the complications of poor control 2.

The landmark ACCORD, ADVANCE, and VADT trials collectively showed that intensive glycemic control (targeting A1C <6.5%) in older adults with established diabetes increased mortality risk without cardiovascular benefit 1. The ACCORD trial was terminated early due to excess mortality in the intensive control arm (HR 1.22) 1.

Current Medication Regimen Assessment

Xigduo (Dapagliflozin 10mg/Metformin 1000mg)

This combination is appropriate and effective:

• Dapagliflozin demonstrated A1C reductions of 0.6-1.4% in clinical trials when added to metformin, with greater reductions in patients with higher baseline A1C 3, 4
• The medication is well-tolerated with low hypoglycemia risk (≤2% in trials), making it suitable for older adults 5
• Additional benefits include modest weight loss (2-3 kg) and blood pressure reduction, both favorable in this population 4, 6
• Primary adverse effects are genital infections (6%) and urinary tract infections (9%), which should be monitored 5

Vascepa (Icosapent Ethyl)

This medication addresses cardiovascular risk and does not affect glycemic control directly.

Specific Management Algorithm

Do NOT intensify diabetes therapy. Instead, follow this approach:

1. Continue current regimen of Xigduo 10/1000 and Vascepa 1

2. Monitor A1C every 3-6 months with target range of 7.0-8.0% 1

3. Screen for medication-related complications:

   • Assess for genital/urinary infections at each visit 6, 5
   • Monitor renal function every 6-12 months (dapagliflozin requires eGFR >45 mL/min/1.73m²) 3
   • Check for signs of volume depletion, especially if on diuretics 6

4. Consider therapy adjustment ONLY if:

   • A1C rises above 8.5% on two consecutive measurements 1
   • Patient develops recurrent infections requiring dapagliflozin discontinuation 6
   • Renal function declines to eGFR <45 mL/min/1.73m² 3

5. Consider deintensification if:

   • A1C falls below 7.0% consistently, to reduce medication burden and hypoglycemia risk 1
   • Patient experiences recurrent hypoglycemia or adverse effects 1

Critical Caveats

Down Syndrome-Specific Considerations

• Individuals with Down syndrome may have altered red blood cell turnover, though this is not universally documented. If there is clinical suspicion of hemoglobin variants or unexplained A1C-glucose discordance, consider using fasting plasma glucose for monitoring instead 1
• Cognitive limitations may affect medication adherence and hypoglycemia recognition, favoring medications with low hypoglycemia risk like SGLT2 inhibitors 1

Avoid Common Pitfalls

• Do not add sulfonylureas or intensify insulin in pursuit of A1C <7%, as this increases hypoglycemia risk without mortality benefit in this population 1
• Do not use point-of-care A1C testing for management decisions; ensure laboratory-based NGSP-certified testing 1, 7
• Do not discontinue SGLT2 inhibitor without cause, as it provides cardiovascular and renal benefits beyond glycemic control 3