HgA1c targets and use of agents for diabetes in older adults

Contributed by: Diana L. Turner, Msc, MD, CCFP, FCFP, Care of the Elderly | Associate Clinical Professor, Department of Family Medicine | University of Calgary

Case

An 82-year-old patient with longstanding type 2 diabetes mellitus (T2DM); multiple comorbidities (hypertension, dyslipidemia, severe degenerative osteoarthritis, GERD, gout and COPD); and self-managed polypharmacy, including insulin. His office visit was triggered by his stressed spouse, as there was a decline in his cognitive function in the last year and he experienced two falls in the last three months.

Issue

HgA1c targets in the older adult, particularly the frail/vulnerable with multiple comorbidities and must be considered in the context of patient/caregiver global function. Hypoglycemic episodes, particularly in the frail elderly, must be avoided.

Literature Review/Best Evidence

There are no randomized controlled trials (RCTs) studying the effect of intensive glycemic control in the frail elderly; hence grade D, consensus, Canadian Diabetes Association (CDA) recommendations.

There are three major trials looking at the effect of intense glycemic control on patients with long-standing type 2 diabetes (ADVANCE, ACCORD and VADT; mean ages 66, 62, and 60, respectively) (^6,7,8,9). All trials demonstrate that there was no cardiovascular benefit associated with intense control of glycemia (HgA1c target achieved 6.4%, 6.4% and 6.9% compared with control aims 7.5%, 7.0% and 8.4%, respectively). The ACCORD trial was stopped prematurely due to increased mortality in the intense control group (not found in the other two studies). All three studies found increased frequency of hypoglycemic events in the intensely controlled groups; the clinical significance of which, for increased morbidity or mortality, remains inconclusive. However, the clinician’s role to promote quality of life and function remains a significant outcome to consider.

Summary from 2013 CDA guidelines, T2DM (^1,2,3,4)

Key Points in treating the metabolically distinct diabetes of the elderly:

• The glycemic targets among the frail elderly of glycated hemoglobin (A1C) are ≤8.5%, and a fasting and preprandial plasma glucose of 5.0 to 12.0 mmol/L.
• Healthy elderly people with diabetes should be treated to achieve the same glycemic, blood pressure and lipid targets as younger people with diabetes.
• Avoiding hypoglycemia is more important than achieving glycemic targets among the frail elderly and those with cognitive impairment.
• Nursing homes should encourage use of regular diets instead of "diabetic diets."

Medication Choices in the elderly

• Unless contraindicated, metformin (MF) should be the initial agent of choice, with additional anti-hyperglycemic agents selected on the basis of clinically relevant issues, such as contraindication to drug, glucose-lowering effectiveness, risk of hypoglycemia and effect on body weight. Avoid MF or use cautiously if glomerular filtration rate (GFR) of kidneys is <30 ml/min.
• Use sulphonylureas (SUs) with caution as the risk of hypoglycemia increases exponentially with age. If SUs are used, start at doses half that used for younger persons and titrate slowly. [SUs have limited usefulness in those with long history T2DM due to limited β‐cell function].
• Instead of glyburide, use gliclazide and glimepiride, as they are associated with a reduced frequency of hypoglycemic events.
• Meglitinides, repaglinide and nateglinide may be used instead of glyburide to reduce the risk of hypoglycemia, particularly if the patient has irregular eating habits.
• Repaglinide is useful when GFR is <30 ml/min.
• Thiazolidinediones should be used with caution due to the increased risk of fractures and heart failure.
• Long-acting basal analogues (NPH, detemir/levemir, glargine/lantus) are associated with a lower frequency of hypoglycemia than conventional insulins in this age group.
• To minimize dose errors: if a mixture of insulin is required, use pre-mixed insulins.
• Detemir and glargine may be used instead of NPH or human 30/70 insulin to lower the frequency of hypoglycemic events.
• Avoid sliding scale insulin, given reactive approach and high risk of hypoglycemia.

Monitoring in the elderly:

• HgA1c every three months is recommended.
• If patient is using insulin more than once a day, self-monitoring of blood glucose (SMBG) should also occur.
• If patient with T2DM is on once-daily insulin in addition to oral anti-hyperglycemic agents, testing at least once a day at variable times is recommended.
• The patient should increase SMBG for treatment adjustments or during acute illness.
• For patients who have managed their T2DM with lifestyle changes, with or without oral anti-hyperglycemic agents associated with low risk of hypoglycemia, and who are meeting glycemic targets, very infrequent SMBF checking may be needed.

Glycemic Target of 7.1-8.5 (^6,7,8,9) for control if:

• Limited life expectancy.
• High level of functional dependency.
• Extensive coronary artery disease at high risk of ischemic events.
• Multiple comorbidities.
• Hypoglycemia unawareness.
• Long-standing diabetics for whom it is difficult to achieve an A1C of ≤ 7%, despite effective doses of multiple anti-hyperglycemic agents, including intensified basal-bolus insulin therapy.

Other Considerations:

• Hypoglycemia has serious consequences for the frail elderly: it is associated with confusion, falls, injuries, weakness, infection and increased risk of death (2). Note that symptoms of hypoglycemia, difficulty concentrating and confusion can worsen the functional abilities in persons with dementia. Conversely persons with dementia will have less ability to manage their diabetes:
  • Diet/nutrition and medication management: insulin dose and injections and prescription doses and timing.
  • Behaviors: they may become agitated with caregivers trying to intervene on their behalf and refuse intervention).
  • Consider how often your elderly patient is home alone, as drug-induced hypoglycemia can be severe and result in loss of consciousness due to coma or seizure.
  • Coping of patient and informal/formal caregiver(s) within their community setting (living alone; home/apartment vs. supportive living vs. long-term care [LTC]).
  • Cognitive and physical function (Compliance: ability and choice).
  • Their dexterity, vision, comprehension and preferences (diet and exercise) and behaviours (collateral history from caregivers).
  • Their social and financial situation (cost of medication) and caregiver stress/burnout (cueing of diet, exercise, medications).
  • Their life expectancy and what they deem to be quality of life.
  • Polypharmacy. Simplify regimes: stop insulin and use oral hypoglycemic, only. Reduce medication dosing regimes from qid to bid or once daily. Stop medications intended for benefit in five-- to- 10 years if life expectancy is less than five years.

References

1. Imran S, Rabasa-Lhoret R, Ross S. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Targets for Glycemic Control. Can J Diabetes 2013;37(suppl 1):S31-S34.
2. Clayton D, Woo V, Yale J-F. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Hypoglycemia. Can J Diabetes 2013;37(suppl 1):S69-S71.
3. Goldenberg R, Punthakee Z. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Definition: Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes 2013;37(suppl 1):S8-S11.
4. Meneilly G, Knip A, Tessier D. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Diabetes in the Elderly. Can J Diabetes 2013;37(suppl 1):S184-190.
5. Lee S, Boscardin W.J., Cenzer I, Huang E, Rice-Trumble K, Eng C. The Risks and Benefits of Implementing Glycemic Control Guidelines in Frail Older Adults with Diabetes Mellitus. JAGS 2011;59(4):666–672.
6. The ACCORD Study Group. Long‐term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364:818‐28.
7. ADVANCE-ON Collaborative Group. Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes. N Engl J Med. September 2014;371:1392-1406.
8. W. Duckworth C. Abraira T. Moritz VADT Investigators Glucose control and vascular complications in veterans with type 2 diabetes N Engl J Med 2009;360:129-139.
9. T. Moritz W. Duckworth C. Abraira Veterans Affairs Diabetes Trial: corrections. N Engl J Med 2009; 361:1024-1025.