Abstract
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 A1c (HbA1c) 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 HbA1c control in the intervention arm compared with the control arm (47 [61.8%] vs 49 [63.6%] with HbA1c <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.