Table 1.

Summary of findings from included studies of L-glutamine (Endari).

Source (Country)	Outcome Measured	Study Design	Age, Years	Group, n	Summary of Findings
Clinical Efficacy
Niihara 2018, USA	Primary: number of pain crises; secondary: hospitalizations, ED visits, changes in hematologic measures	RCT	5–58, median 19 in treatment group, 17 in placebo	230	-Pain crises: median 3 in treatment group, 4 in placebo (p = 0.005) -Hospitalizations: median 2 in treatment, 3 in placebo (p = 0.005) -ED visits: did not differ significantly (1 in both) -No significant between-group differences in the change in hemoglobin level, hematocrit level, or reticulocyte count -Cumulative number of pain crises was 25% lower in the l-glutamine group than in the placebo group over the entire 48-week treatment period -Time to first pain crisis: 84 vs. 54 days (HR 0.69, p = 0.02) -Time to second crisis: 212 vs. 133 (HR 0.68, p = 0.03) -ACS: 8.6% vs. 23.1%, p = 0.003 -Days in hospital: 6.5 vs. 11, p = 0.02 -Adverse events higher in placebo vs. L-glutamine (100% vs. 98.0%), as was serious adverse events (87.1% vs. 78.2%)
Niihara 2018, USA	Number of crises	Subgroup analysis of Niihara et al.	5–58, median 19 in treatment group, 17 in placebo	230	-Rate ratios of pain crises similar in all subgroups (based on # of crises in year prior to study): 0.87, 0.74, and 0.82 for 2, 3–5, and ≥6 SCC in year prior, respectively
Lam 2021, USA	Number of transfusions	Post hoc of Niihara et al.	5–58, median 19 in treatment group, 17 in placebo	230	-2.86 units transfused per year in treatment vs. 5.38 in placebo (p = 0.0253) -1.702 RBC transfusion episodes per patient-year in the L-glutamine arm vs. 2.659 in placebo (p = 0.0783)
Wilson 2019, USA	Opioid use	Case series	Range 9–24	4	-All 4 patients had decreased opioid use, 21–100% decrease -No difference in average hemoglobin -1 patient went from 3 ED visits + 2 hospitalizations to 0 in post-treatment period
Side Effects and Prescribing Data
Gotesman 2020, USA	Prescribing data, compliance	Retrospective review	Mean 9.1	50	-83% of patients 5y and older prescribed L-glutamine, 70% were dispensed -Some refused due to taste or abdominal pain -One-fourth of patients had <50% intake while on both HU and L-glutamine; overall compliance was ≥70% in 12 patients -Of 10 patients, mean number of crises decreased 0.9 to 0.2, p = 0.016
Ogu 2019, USA	Compliance, side effects	Retrospective review	Mean 36, range 21–70	111	-At end of 14-month period, 19% were actively taking L-glutamine, 42% discontinued, 35% never filled, 4% received but did not start -Mean fill rate: 1.79 fills, 2.51 for patients who filled more than once -47% filled two times or fewer -Median day to stopping 47 days -Barriers to initiating: 38% prior authorization (PA) denied, 21% high deductible, 10% other insurance issues -Reasons to stopping: 35% poor adherence, 13% side effects, 4% pregnant, 4% no perceived benefit -GI side effects: nausea, abdominal pain, and constipation