Table 1.

Evidence to recommendations table: Does deprescribing (complete cessation of all antihyperglycemic agents, reduction of 50% of insulin dose [in patients with a total insulin dose > 20 units/d], cessation of glyburide, switching from glyburide to another SU) antihyperglycemic medications compared with continuous antihyperglycemic medication use result in benefit or harms in adults > 65 y (community dwelling and in long-term care)?

DECISION DOMAINSUMMARY OF REASON FOR DECISIONSUBDOMAINS INFLUENCING DECISION
QoE: Is there high-or moderate-quality evidence?
Yes ☑ No ☑
QoE: very low
  • There were 2 controlled before-and-after studies at high risk of bias and there were concerns about imprecision. There was no difference in hypoglycemia between deprescribing and control arms (RR = 1.08, 95% CI 0.78 to 1.50), no difference in HbA1c level after stopping glyburide vs continuing (MD = 0.02% lower, 95% CI −0.16% to 0.12%), and a non-significant increase in HbA1c level for complete cessation of antihyperglycemic agents vs continuation (MD = 1.1% increase, 95% CI −0.56% to 1.64%)

NA
Balance of benefits and harms: Is there certainty that the benefits of deprescribing outweigh the harms? Yes ☑ No □
Is there certainty that the benefits of continued use outweigh the harms? Yes ☑ No ☑
Our target population is individuals > 65 y, specifically those at high risk of hypoglycemia (eg, owing to overly intense glycemic control, multiple comorbidities, drug interactions, hypoglycemia history or lack of awareness), those at high risk of other adverse effects (eg, owing to reduced renal function), and those in whom benefit is uncertain owing to frailty, dementia, or limited life expectancy. Our systematic review demonstrated that deprescribing antihyperglycemic agents does not result in clinically concerning increases in blood glucose levels in nursing home patients and community-dwelling elderly patients, although there is no evidence that deprescribing reduces incidence of hypoglycemia
  • A review of harms suggests intensive blood glucose control is associated with increased risk of severe hypoglycemia (RR = 2.18, 95% CI 1.53 to 3.11) and increased risk of adverse drug events (hospitalizations and life-threatening events). Risk of hypoglycemia and its consequences is known to be increased in older persons

  • Intensive blood glucose control does not reduce risk of all-cause or cardiac mortality; however, it can reduce nonfatal MI risk, and risk of microvascular complications

  • Guidelines suggest less intensive blood glucose control in frail patients and those with limited life expectancy

Is the baseline risk for benefit of deprescribing similar across subgroups?
Yes ☑ No □
  • No evidence of a difference across subgroups


Is the baseline risk for harm from deprescribing similar across subgroups?
Yes ☑ No □
Should there be separate recommendations for subgroups based on risk levels for harm from deprescribing?
Yes ☑ No ☑
  • Recommendations apply to adults > 65 y who are receiving ≥ 1 antihyperglycemic medications to treat type 2 diabetes and who are at high risk of hypoglycemia (eg, owing to age, overly intense glycemic control, multiple comorbidities, drug interactions, hypoglycemia history or lack of awareness, or impaired renal function) or other adverse effects, or in whom benefit is uncertain owing to frailty, dementia, or limited life expectancy


Is the baseline risk for benefit of continued use similar across subgroups? Yes ☑ No □
Is the baseline risk for harm from continued use similar across subgroups? Yes ☑ No □
  • No evidence that harm differs based on subgroup Should there be separate recommendations for subgroups based on harms of continued use? Yes ☑ No ☑

  • No evidence that harms or benefits differ based on subgroup

Values and preferences: Is there confidence in the estimate of relative importance of outcomes and patient preferences?
Yes ☑ No ☑
(See references 119–122, 124, 127, 129, and 132 in the evidence reviews at CFPlus*)
Patients view insulin therapy and frequent self-monitoring of blood glucose as burdensome. Older patients with diabetes tend to have goals focused on maintaining independence and social function vs risk control or prevention of complications; therefore, burden of care is more important than strict adherence and intensive therapy. Hypoglycemia can negatively affect QoL and function. Goals and preferences surrounding intensity of treatment appear to be variable, and patient goals, time to benefit, and complexity should be discussed when developing treatment plans. Many patients will prefer less intensive treatment, although some might prefer more aggressive treatmentPerspective taken: patient perspective—we have taken the view that many older patients see intensive treatment as burdensome and the consequences of intensive treatment such as hypoglycemia negatively affect QoL. Older persons tend to value independence, function, and QoL over risk reduction and reduced mortality
Source of values and preferences: nonsystematic literature review
Source of variability, if any: cannot estimate
Method for determining values satisfactory for this recommendation?
Yes ☑ No □
All critical outcomes measured?
Yes ☑ No □
  • Further evidence would be helpful to fully elucidate patient values and preferences but available evidence was clear

Resource implications: Are the resources worth the expected net benefit?
Yes ☑ No □
(See references 136 and 137 in the evidence reviews at CFPlus*)
Patients experiencing hypoglycemia show increased annual diabetes-related (and overall) health costs vs those without hypoglycemia (MD = $5024, P < .0001). Decision tree analysis suggests insulin and SUs might not be cost effective in older persons owing to the risk of hypoglycemia and associated eventsFeasibility: is this intervention generally available?
Yes ☑ No □
  • Deprescribing is available at all levels of care by various health care providers


Opportunity cost: is this intervention and its effects worth withdrawing or not allocating resources from other interventions?
Yes ☑ No □
  • Unclear—deprescribing aims to reduce downstream health care and resource use; however, there is no evidence of this currently. Deprescribing is unlikely to necessitate allocating resources from other interventions

Is there a lot of variability in resource requirements across settings? Yes ☑ No ☑
  • Deprescribing can be executed at all levels of care by various health care providers

Strength of main recommendation: strongOur systematic review showed that deprescribing did not produce a clinically concerning increase in blood glucose levels (as shown by HbA1c outcomes), although the QoE was very low. Evidence suggests no benefit associated with intensive blood glucose control in the elderly and potential for harm (increased risk of hypoglycemia). Older persons (specifically, frail elderly) are at higher risk of hypoglycemia. Survey data and interviews suggest hypoglycemia is associated with lower QoL in older persons. The elderly tend to value lower treatment burden, independence, and function above risk reduction from intensive therapy. Patients with hypoglycemia produce increased diabetes-related health care costs vs those without hypoglycemia, and insulin or SUs might not be cost effective in older persons owing to hypoglycemia
  • HbA1c—hemoglobin A1c, MD—mean difference, MI—myocardial infarction, NA—not applicable, QoE—quality of evidence, QoL—quality of life, RR—relative risk, SU—sulfonylurea.