What are the updated guidelines for diabetes management in ADA 2025, including first-line and second-line treatments and target HbA1c (hemoglobin A1c) levels?

HbA1c Terminology Update in ADA 2025 Guidelines

The ADA 2025 guidelines maintain the standard HbA1c terminology without introducing new classification systems, continuing to use HbA1c <7.0% (53 mmol/mol) as the general target for most nonpregnant adults with diabetes. 1

Core Terminology Remains Unchanged

The 2025 ADA Standards of Care preserve the established HbA1c nomenclature and measurement standards that have been in place:

• Standard target: HbA1c <7.0% (53 mmol/mol) for most nonpregnant adults 1
• Dual reporting: HbA1c continues to be reported both as percentage and in mmol/mol units 1
• Measurement frequency: Test at least twice yearly for stable patients meeting goals; quarterly for those not meeting targets or with therapy changes 2

Key Terminology Clarifications in 2025

Hypoglycemia Classification System

The 2025 guidelines reinforce the three-level hypoglycemia classification that has become standard:

• Level 1: Blood glucose <70 mg/dL (3.9 mmol/L) - alert value requiring action 1
• Level 2: Blood glucose <54 mg/dL (3.0 mmol/L) - clinically significant hypoglycemia 1
• Level 3: Severe cognitive impairment requiring external assistance 1

Individualization Framework Language

The 2025 guidelines emphasize individualized glycemic goals rather than one-size-fits-all targets, using specific terminology for different patient populations 1:

• More stringent targets (HbA1c <6.5%): For newly diagnosed patients with long life expectancy, no cardiovascular disease, and low hypoglycemia risk 2
• Standard targets (HbA1c <7.0%): For most nonpregnant adults 1
• Less stringent targets (HbA1c up to 8.0%): For patients with limited life expectancy, severe comorbidities, or high hypoglycemia risk 1, 2

Critical Threshold Terminology

Treatment Intensification Thresholds

The 2025 guidelines specify precise HbA1c thresholds for treatment decisions:

• HbA1c ≥1.5% above goal: Requires dual-combination therapy or more potent glucose-lowering agent 1
• HbA1c >10% (>86 mmol/mol): Consider insulin initiation regardless of background therapy if symptoms present 1
• Blood glucose ≥300 mg/dL (≥16.7 mmol/L): Consider insulin initiation regardless of HbA1c 1

Deintensification Language

The 2025 guidelines introduce stronger language around deintensification of therapy, emphasizing that clinicians should actively reduce or stop medications when risks exceed benefits 1. This represents a shift toward more explicit terminology about stepping down therapy, particularly for medications causing hypoglycemia (insulin, sulfonylureas, meglitinides) 1.

Comorbidity-Specific Terminology

The 2025 guidelines maintain terminology linking HbA1c targets to specific comorbidities:

• Cardiovascular disease (CVD): No change in terminology; HbA1c targets remain individualized based on CVD presence 1
• Chronic kidney disease (CKD): HbA1c terminology unchanged; targets individualized based on kidney function 1
• Metabolic dysfunction-associated steatohepatitis (MASH): New emphasis on considering MASH risk when selecting glucose-lowering therapy, though HbA1c terminology itself unchanged 1

Medication-Specific HbA1c Language

First-Line Therapy Terminology

Metformin remains described as "commonly used" first-line medication for patients without additional considerations beyond glucose lowering, though the 2025 guidelines soften previous absolute language about metformin being "the" first-line agent 1. This reflects growing recognition that GLP-1 receptor agonists and SGLT2 inhibitors may be preferred first-line for patients with cardiovascular or kidney disease 1.

Combination Therapy Terminology

The 2025 guidelines use specific language about "higher-efficacy approaches, including combination therapy" having greater likelihood of achieving treatment goals 1. This represents a shift toward more aggressive initial combination therapy rather than sequential monotherapy escalation.

Common Pitfalls in HbA1c Terminology

• Avoid using HbA1c as sole metric: The 2025 guidelines emphasize that HbA1c should be interpreted alongside continuous glucose monitoring metrics (time in range, time below range) when available 1
• Don't ignore non-glycemic factors: Conditions affecting red blood cell turnover (anemia, hemoglobinopathies, kidney disease) can falsely elevate or lower HbA1c independent of glucose control 3
• Recognize "metabolic memory" terminology: The guidelines continue using this term to describe how intensive early glycemic control provides long-term benefits even if control later relaxes 1

No New Diagnostic Terminology

The 2025 ADA guidelines do not introduce new HbA1c cutoffs for diabetes diagnosis, maintaining:

• Diabetes diagnosis: HbA1c ≥6.5% (48 mmol/mol) 4
• Prediabetes range: HbA1c 5.7-6.4% (39-47 mmol/mol) [general medical knowledge]