Can We Deintensify Treatment in Older Type 2 Diabetes Patients?

As a person ages, the concern comes up as to whether to deintensify treatment to prevent problems of falls and other possible injuries.

Relevant studies were identified in a literature search of MEDLINE, Embase, Web of Science, and Cochrane databases to October 2018. Data was extracted on baseline characteristics.

Guideline bodies recommend less strict glycemic targets in older people with diabetes. It is uncertain whether the benefits of deintensification or de-prescribing, commonly employed by clinicians to achieve the less strict targets, outweighs the harms in these patients. A systematic review was conducted of published evidence, to assess deintensification approaches and rates and evaluate the harms and benefits of deintensification with antidiabetic medication and other therapies amongst older people (≥ 65 years) with type 2 diabetes with or without cardiometabolic conditions.

In this meta-analysis, the authors evaluated the effects of deintensification of antihyperglycemic medications in elderly patients. While some studies looked at the effects of reduced dosages or changes in medication, most of the studies evaluated complete discontinuation of antihyperglycemic treatment. HbA1c levels remained largely stable after deintensification and increases in falls and hospitalizations were not associated with deintensification. Adverse event rates were similar in patients who continued on therapy compared with those who discontinued treatment.

Ten studies (observational cohorts and interventional studies) with data on 26,558 patients with comorbidities were eligible. Deintensification approaches included complete withdrawal, discontinuation, reducing dosage, conversion, or substitution of at least one medication, but the majority of studies were based on complete withdrawal or discontinuation of antihyperglycemic medication. Rates of deintensification approaches ranged from 13.4% to 75%. The majority of studies reported no deterioration in HbA1c levels, hypoglycemic episodes falls or hospitalization on deintensification. On adverse events and mortality, no significant differences were observed between the comparison groups in the majority of studies. ‘

In seven of the studies they looked at outcomes of glycemic control after deintensification approaches. In two studies that compared discontinuation or reduction in dose of antihyperglycemic medication with usual care, no significant differences were found in HbA1c levels. In one study, there was no significant difference in hypoglycemia rates between the groups post-intervention. In eight patients who had their hypoglycemic medications completely withdrawn over 3-6 months and followed up for a year, there was no significant difference between the mean HbA1c at the point of hypoglycemic medications withdrawal and at 1 year of follow-up. In 5 patients with type 2 diabetes and on hemodialysis, discontinuation of insulin and other oral hypoglycemic agents and switching to liraglutide caused reduction in levels of HbA1c and hypoglycemic episodes. In two studies that evaluated switching from one antihyperglycemic agent to another, no adverse events were recorded in both studies. In a study comparing patients whose antihyperglycemic therapy was discontinued on discharge versus those discharged on antihyperglycemic therapy in Medicare beneficiaries admitted on diabetes medication, rates of readmissions did not differ significantly between the two groups. When insulin and other oral hypoglycemic medications were switched to liraglutide in five patients on hemodialysis, there was improved quality of life in more than half of the patients.

In the study by Sjoblom and colleagues, which compared complete withdrawal or reduction in dose of antihyperglycemic medication with usual care, there was no significant difference in the risk of mortality for the deintensification group compared to the non-intervention group.

In conclusion, available but limited evidence based on mixed study designs suggest that the benefits of deintensification outweighs the harms in older people with type 2 diabetes with or without comorbidities. The data also suggests deprescribing is feasible. There are still some unanswered questions. There is limited information to guide which deprescribing approaches to use in order to achieve safe individual targets in older patients. The appropriate glycemic control targets in such patients are also uncertain. Guideline bodies have started to recognize the harms of overtreatment in older patients with diabetes and several recommendations have been made to reflect the heterogeneity of these patients.

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) guidelines for diabetes treatment recommend an individualized approach based on the preference of the patient, comorbidities, severity of diabetes-related complications, and life expectancy.

Even though the evidence was limited, it suggests that the benefits of deintensification outweigh the harms in older people with type 2 diabetes with or without comorbidities. Given the heterogeneity of patients with diabetes, further research is warranted on which deintensification approaches are appropriate and beneficial for each specific patient population.

Practice Pearls:

• Only a few older patients with type 2 diabetes and complex comorbidities actually gain substantial benefit from intensive management.
• A number of RCTs have shown that intensive glycemic control directed at lower HbA1c targets is associated with only minor cardiovascular benefits but increased adverse events such as mortality.
• Evidence shows that older people with type 2 diabetes and other comorbidities are being overtreated with drugs that cause hypoglycemia.
• The need for deintensification approaches with personalized treatments  is therefore of substantial relevance in healthcare.

Diabetes, Obesity and Metabolism April 2019 https://doi.org/10.1111/dom.13724