Initiation of antipsychotic therapy associated with hyperglycemia in older diabetic patients

A case-control analysis published in the Archives of Internal Medicine demonstrated that the initiation of antipsychotic therapy in older adults with diabetes was associated with a significantly increased risk of hyperglycemia requiring hospitalization. This risk was particularly high in patients who were being treated with antipsychotics for the first time.

Researchers used data from the National Ambulatory Care Reporting System database, the Canadian Institute for Health Information Discharge Abstract Database, the Ontario Health Insurance Plan database, and the Ontario Diabetes Database to identify patients eligible for inclusion in this nested, case-control study. Eligible patients were those aged at least 66 years who had preexisting diabetes and who began therapy with an antipsychotic drug between April 1, 2002, and March 31, 2006. Patients who had received an antipsychotic prescription within the previous year were not eligible for inclusion. Researchers stratified eligible patients by diabetes treatment (insulin treatment, treatment with oral hypoglycemic agent, or no treatment) based on prescription records from the 6 months before study entry.

Case patients were those who were hospitalized with hyperglycemia during the study period. Each case was matched with up to 10 control patients on the basis of age, sex, year of cohort entry, and duration of follow-up.

A total of 13,817 patients were included in the study cohort; patients were followed for an average of 2 years. During follow-up, 1,515 patients (11%) were hospitalized with hyperglycemia; 479 of these patients had been treated with insulin, 823 had been treated with an oral hypoglycemic agent, and 213 had not received diabetes medications. Compared with no antipsychotic use, current antipsychotic use was associated with a significantly higher risk of hyperglycemia (adjusted rate ratio, 1.5; 95% CI, 1.29–1.74; P P=.02; adjusted rate ratio among patients treated with oral hypoglycemic agents, 1.36; 95% CI, 1.12–1.66; P=.002; adjusted rate ratio among patients with no diabetes treatment, 2.43; 95% CI, 1.29–1.74; P
Among patients who were being treated with antipsychotics for the first time (ie, only 1 prescription before the index [event] date), nearly 70% of hyperglycemic events occurred within 14 days of treatment initiation. Patients newly treated with antipsychotics also demonstrated markedly higher rates of hyperglycemia versus untreated patients, with adjusted rate ratios ranging from 8.98 to 15.4. Patients with ongoing antipsychotic use (ie, >1 prescription before the index date) also demonstrated significantly higher rates of hyperglycemia versus untreated patients, with adjusted rate ratios ranging from 1.31 to 2.23.

The investigators discussed the potential for confounding of the study results by factors associated with both antipsychotic agents and hyperglycemia. Such confounders could include underlying risk factors for hyperglycemia in patients who need antipsychotic therapy, including acute psychiatric stress, nonadherence to diabetes medications, and concurrent illness. Although the researchers attempted to address these issues in their study design, they pointed out that “a causal relationship between antipsychotic agents and hyperglycemia cannot be concluded based on our observational study.” They suggested that further studies are needed; in the meantime, they stated that “other options to manage behavioral symptoms of dementia should be considered among older persons with diabetes.” The authors also noted that their results “highlight the importance of enhanced glycemic monitoring when antipsychotic therapy is initiated in patients with diabetes.”

Source
Lipscombe LL, Levesque L, Gruneir A, et al. Antipsychotic drugs and hyperglycemia in older patients with diabetes. Arch Intern Med. 2009;169:1282–1289.