Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus.

BACKGROUND: Intra-articular (IA) corticosteroid injections may cause hyperglycemia (glucose level > 180 mg/dL). In a phase 2 study of 33 patients who had osteoarthritis of the knee (OAK) and type 2 diabetes mellitus (T2D), triamcinolone acetonide extended-release (TA-ER) was associated with minimal glycemic control disruption compared with triamcinolone acetonide immediate-release (TA-IR). This post hoc analysis characterizes the clinical relevance of these results. METHODS: Patients who had symptomatic OAK for ≥ 6 months, T2D for ≥ 1 year, and hemoglobin A1c ≥ 6.5 and ≤ 9.0% were randomized to receive an IA injection of either TA-ER or TA-IR. Changes in continuous glucose monitor daily glucose level, percentage of time in or above the target glucose range (> 70 to 180 mg/dL), time to glucose level 250 mg/dL and maximum glucose level > 250 mg/dL, and glycemic variability were evaluated. RESULTS: Across postinjection days 1 to 3, the TA-ER group (n = 18) had a lower median change from baseline in maximum glucose level (92.3 versus 169.1 mg/dL), a reduced percentage of time with a glucose level > 250 mg/dL (12 versus 26%), a smaller proportion of patients who had a maximum glucose level > 250 mg/dL (50 versus 93%), and a greater percentage of time in the target glucose range (62 versus 48%) versus the TA-IR group (n = 15). There was less glycemic variability and lower glucose spikes in the TA-ER versus TA-IR group. Median times to glucose level 250 mg/dL (44 versus 6 hours) and maximum glucose level (34 versus 13 hours) were significantly longer in the TA-ER versus TA-IR group. CONCLUSIONS: Use of TA-ER was associated with a clinically meaningful reduction in hyperglycemia versus TA-IR.

A phase 3 active-controlled trial of liposomal bupivacaine via sciatic nerve block in the popliteal fossa after bunionectomy.

STUDY OBJECTIVE: To investigate the efficacy, safety, pharmacodynamics, and pharmacokinetics of liposomal bupivacaine (LB) administered via ultrasound-guided sciatic nerve block in the popliteal fossa in participants undergoing bunionectomy. DESIGN: Two-part, randomized, double-blind, active-controlled trial (NCT05157841). SETTING: Operating room, postanesthesia care unit, and health care facility (6 sites). PATIENTS: Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy. INTERVENTIONS: Part A participants were randomized 1:1:1 to LB 266 mg, LB 133 mg, or bupivacaine hydrochloride 50 mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI. MEASUREMENTS: The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96 h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96 h after surgery, and pharmacokinetic endpoints. MAIN RESULTS: Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133 mg (n = 59) and BUPI (n = 60) (185 total). LB 133 mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; P < 0.00001) and total opioid consumption 0-96 h after surgery (LSM, 17.7 [95% confidence interval (CI), 13.7, 22.8] morphine milligram equivalents [MMEs] vs 45.3 [95% CI, 35.1, 58.5] MMEs; P < 0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; P = 0.0003) in parts A + B. Adverse events were similar across groups. CONCLUSIONS: LB 133 mg administered via sciatic nerve block in the popliteal fossa after bunionectomy demonstrated superior and long-lasting postsurgical pain control versus BUPI. The clinical relevance of these findings is supported by concurrent reductions in pain and opioid consumption over 4 days after surgery and a significantly greater percentage of participants remaining opioid-free.