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Hemoglobin A1c Targets for Type 2 Diabetes Mellitus

SUMMARY:

The ACP provides guidance to help providers better target hemoglobin A1c (HbA1c) targets for the pharmacologic treatment of type 2 diabetes. The ACP recommends

Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of benefits and harms of pharmacotherapy, patients’ preferences, patients’ general health and life expectancy, treatment burden, and costs of care

Clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes

Clinicians should consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%

Clinicians should treat patients with type 2 diabetes to minimize symptoms related to hyperglycemia and avoid targeting an HbA1c level in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population

KEY POINTS:  

Other guidelines reviewed in this document include  

  • The ADA guidelines set the following targets
    • <7% for the general population 
    • Less stringent A1C goals (e.g., < 8%) may be appropriate for patients with limited life expectancy or where the harms outweigh the benefits 
    • Consider more stringent goals (<7%) for selected patients without significant hypoglycemia
      • Short duration of diabetes 
      • Type 2 diabetes treated with lifestyle or metformin only 
      • Long life expectancy 
      • No CVD  

Note: The ADA issued a statement that it is “deeply concerned by the new guidance” and “that a reasonable A1c goal for many nonpregnant adults with type 2 diabetes is less than 7 percent based on the available evidence to date from the ACCORD, ADVANCE, VADT and UKPDS international clinical trials, which were evaluated and incorporated into ADA’s Standards of Care.” (see ‘Learn More – Primary Sources’ below)

  • Scottish Intercollegiate Guidelines Network (SIGN) guideline is similar to ADA  
  • AACE/ACE
    • ≤6.5% if target can be achieved safely  
  • NICE
    • 6.5% for patients managed with
      • Lifestyle and diet 
      • Lifestyle and diet with single drug and no hypoglycemia 
    • 7% for patients on medications associated with hypoglycemia  
  • Institute for Clinical Systems Improvement
    • < 7% to < 8% based on patient factors 
  • VA/DoD
    • 6% to 7% for patients with a life expectancy > 10 to 15 years and no or mild microvascular complications 
    • 7% to 8.5% for those with established microvascular or macrovascular disease, comorbid conditions, or a life expectancy of 5 to 10 years 
    • 8% to 9% for those with a life expectancy <5 years, significant comorbid conditions, advanced complications of diabetes, or difficulties in self-management attributable to mental status, disability, or other factors (12) 

Review of Literature 

Overall, the ACP did not find that the benefits of lower HbA1c targets justified potential risks 

  • ACP reviewed 5 large RCTs comparing intensive (achieved HbA1c levels, 6.3% to 7.4%) versus less intensive (achieved HbA1c levels, 7.3% to 8.4%) treatment targets
    • Main effect: More intensive glycemic control resulted in small absolute reductions in risk for microvascular surrogate events (e.g., retinopathy on ophthalmologic screening) but not clinical events such as loss of vision  
    • One trial of metformin in overweight adults showed a reduction in all-cause and diabetes-related death through at least 10 years 
    • In all studies, more intensive therapy required higher dose medications and was associated with more adverse events (including increased risk of death in 1 study) 

NOTE: All guidelines allow for higher HbA1c targets depending on comorbid conditions and limited life expectancy 

Learn More – Primary Sources:  

Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians

American Diabetes Association® Deeply Concerned About New Guidance from American College of Physicians Regarding Blood Glucose Targets for People with Type 2 Diabetes

ADA: Glycemic Targets: Standards of Medical Care in Diabetes—2023

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM – 2020 EXECUTIVE SUMMARY

NICE: Type 2 diabetes in adults: management

VA/DoD Clinical Practice Guidelines: Management of Diabetes Mellitus in Primary Care

Prediabetes and Diabetes Type 2: Screening and Making the Diagnosis

Clinical Actions:

Diabetes results from the impaired secretion of insulin or resistance to its peripheral effects, leading to abnormal metabolism of carbohydrates and elevated levels of glucose in the blood and urine. Type 2 diabetes (previously “noninsulin-dependent diabetes” or “adult-onset diabetes”) accounts for 90–95% of all diabetes. Type 2 diabetes is caused by a progressive loss of β-cell insulin secretion, usually associated with insulin resistance. Prediabetes is diagnosed when glucose levels start to rise due to β-cell insulin secretion failure, but diagnostic criteria are not yet met for Type 2 diabetes.

Table of Contents  

Evaluate Patients for Risk Factors

Risk Factors for Type 2 Diabetes (NIDDK)

  • Overweight or obese
    • NIDDK BMI chart (see ‘Primary Sources – Learn More’ below)
      • Not Asian American or Pacific Islander: At-risk BMI ≥ 25
      • Asian American: At-risk BMI ≥ 23
      • Pacific Islander: At-risk BMI ≥ 26
  • ≥45 years
  • Family history of diabetes
  • Race/Ethnicity
    • African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander
  • Hypertension (or on therapy for hypertension)
  • Dyslipidemia
  • Personal history of
    • Pregnancy: GDM or macrosomia (BW >4000 g)
    • Physical inactivity
    • Heart disease or stroke
    • Depression
    • PCOS
    • Acanthosis nigricans
    • HIV

Screening and Diagnostic Criteria

Who and When to Screen

ADA

  • Overweight or obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) and ≥1 of the following risk factors
    • First-degree relative with diabetes
    • High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)
    • History of CVD
    • Hypertension (≥140/90 mmHg or on therapy for hypertension)
    • HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)
    • Women with polycystic ovary syndrome
    • Physical inactivity
    • Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
  • People with HIV
    • Screen for diabetes and prediabetes with a fasting glucose test
      • Before starting antiretroviral therapy
      • At the time of switching antiretroviral therapy
      • 3 to 6 months after starting or switching antiretroviral therapy
    • If initial screening results are normal, fasting glucose should be checked annually
  • Patients with prediabetes (A1C ≥5.7% [39 mmol/mol], IGT, or IFG) should be tested yearly
  • Women who were diagnosed with GDM should have lifelong testing at least every 3 years
  • For all other patients, testing should begin at age 35 years
  • If results are normal, testing should be repeated at a minimum of 3-year intervals, with consideration of more frequent testing depending on initial results and risk status

AACE/ACE

  • Begin at age 45 without risk factors
  • Screening based on risk factors: In addition to the above list, AACE/ACE includes the following factors
    • Antipsychotic therapy for schizophrenia and/or severe bipolar disease
    • Chronic glucocorticoid exposure
    • Sleep disorders (e.g., obstructive sleep apnea, chronic sleep deprivation, and night shift occupation) with glucose intolerance
  • Normal glucose values: Every 3 years
  • Consider annual screening for patients with 2 or more risk factors

USPSTF

  • Screen for prediabetes and type 2 diabetes in adults aged 35 to 70 years who have overweight (BMI ≥25) or obesity (BMI ≥30)
  • Clinicians should offer or refer patients with prediabetes to effective preventive interventions
  • Above are Grade B recommendations: Offer or provide this service

Diagnostic Criteria

  • Normal
    • Fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol per L)
    • Oral glucose tolerance test (OGTT) with 75g glucose load
      • 2h (plasma glucose) PG <140 mg/dL (7.8 mmol per L)
  • High Risk for Diabetes (prediabetes)
    • Impaired fasting glucose (IFG): FPG ≥100 to 125 mg/dL (5.6 to 6.9 mmol per L)
    • Impaired glucose tolerance (IGT): 2h PG ≥140 to 199 mg/dL (7.8 to 11.0 mmol per L)
    • A1C 5.7% to 6.4%
    • Note: Patients with prediabetes should be tested yearly
  • Diabetes: Glucose criteria are preferred for the diagnosis of DM
    • FPG ≥126 (7.0 mmol per L) mg/dL
    • OGTT: 2h PG ≥200 mg/dL (11.1 mmol per L)
    • Random PG ≥200 mg/dL (11.1 mmol per L) with the following symptoms of hyperglycemia
      • Polydipsia | Polyuria | Polyphagia | Blurred vision | Weakness | Unexplained weight loss
    • A1C ≥6.5%
    • Note: Always confirm diabetes diagnosis with repeat glucose or A1C testing on another day

SYNOPSIS:

Prediabetes is not a clinical disorder but rather an important risk factor for diabetes and cardiovascular disease. While there are some differences between organizations regarding risk factors for screening and diagnostic cut-offs, all agree as to the importance of identifying those at risk for significant cardiovascular events if diabetes is left untreated. The prognosis for type 2 diabetes varies and is very dependent on glucose control.

KEY POINTS:

Symptoms of Diabetes (related to hyperglycemia)

  • Excessive urination, thirst and hunger 
  • Unexpected weight loss 
  • Increased susceptibility to infections, especially yeast or fungal infections 
  • Weak, tired feeling
  • Dry mouth
  • Blurry vision
  • Deposits of blood, or puffy yellow spots in the retina
  • Decreased sensation in the legs
  • Weak pulses in the feet
  • Blisters, ulcers or infections of the feet 

Complications of Type 2 Diabetes

  • Atherosclerosis
  • Retinopathy 
  • Neuropathy 
  • Nephropathy
  • Dermatologic pathology
    • Infections
    • Feet in particular: Ulcerations with poor healing  

Learn More – Primary Sources:

ADA: Classification and Diagnosis of Diabetes: Standards of Care in Diabetes – 2023

AACE/ACE Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan

Consensus Statement By The American Association Of Clinical Endocrinologists And American College Of Endocrinology On The Comprehensive Type 2 Diabetes Management Algorithm – 2020 Executive Summary

NIDDK: Risk Factors for Type 2 Diabetes

60-Second Type 2 Diabetes Risk Test

USPSTF: Screening for Prediabetes and Type 2 Diabetes

HIV and Diabetes | NIH