Pharmacist Intervention for Safer Prescribing in Patients With Type 2 Diabetes at High Risk

Importance Severe hypoglycemia is a life-threatening, iatrogenic complication of diabetes medications associated with increased risks of falls, cardiovascular events, cognitive decline, and mortality. Objective To determine whether proactive outreach by a clinical pharmacist applying an evidence-based hypoglycemia-prevention algorithm (Hypoglycemia on a Page) would result in safer prescribing of diabetes regimens among patients with type 2 diabetes (T2D) with hypoglycemia risk. Design, Setting, and Participants This randomized clinical trial was conducted between July 20, 2023, and January 22, 2024, with follow-up outcomes collected through January 2025. The study included adults with T2D at high risk of hypoglycemia based on a validated hypoglycemia risk tool. The trial was conducted within Kaiser Permanente Northern California, a large, integrated health care delivery system. Intervention Patients were randomized 1:1 to either a protocol-driven outreach by a clinical pharmacist (intervention) arm or a usual care (control) arm. Main Outcome and Measure The main outcome was the comparison of the proportion of patients who were prescribed safer (less hypoglycemia-prone) diabetes regimens, defined as discontinuation of sulfonylureas and/or rapid-acting or short-acting or mixed insulins, using an intention-to-treat analysis. Results From an eligible population of 1204 patients, 200 were enrolled into the clinical trial. Among these, 191 patients were in the intention-to-treat cohort (mean [SD] age, 71.3 [11.5] years; 100 females [52.4%]). The 2 study arms were similar at baseline in terms of race and ethnicity, sex, mean (SD) hemoglobin A 1c (HbA 1c ) level (intervention: 8.0 [1.3]; control: 8.3 [1.8]), and number (percentage) of patients receiving insulin (intervention: 82 [85.4%]; control:85 [89.5%]) and sulfonylurea (intervention: 25 [26.0%]; control: 21 [22.1%]). At 6 months, patients in the intervention arm were more likely to be prescribed a safer diabetes regimen than those in the control arm (27 [28.1%] vs 15 [15.8%]; risk difference [RD], 12.3% [95% CI, 0.6% to 24.0%]). Patients in the intervention arm also experienced significantly fewer hypoglycemia-related emergency department or inpatient encounters (0 vs 5 [5.3%]; RD, −5.3% [95% CI, −11.8% to −1.3%]). There was no worsening of HbA 1c control in the intervention arm compared with the control arm (47 [61.8%] vs 49 [63.6%] with HbA 1c <8%; RD, −1.8% [95% CI, −17.0% to 13.5%]). Conclusions and Relevance In this randomized clinical trial, adding proactive, protocol-driven clinical pharmacist outreach into collaborative team-based care improved medication optimization and patient outcomes. This approach provides an evidence-based strategy for reducing the risk of developing severe hypoglycemia in individuals with T2D at high risk, enhancing patient safety, and potentially reducing overall health care cost. Trial Registration ClinicalTrials.gov Identifier: NCT06746714