Evaluation of teplizumab's efficacy and safety in treatment of type 1 diabetes mellitus: A systematic review and meta-analysis

Table 1 Database search strategy

Database	Search strategy
Scopus	11 “Type-1 Diabetes mellitus” OR “T1DM” OR “Teplizumab” OR “anti-CD3 monoclonal antibody”
	12 “Insulin” OR “Glycated hemoglobin A1c” OR “HbA1C” OR “C-peptide” OR “Adverse events” OR “Randomized controlled trials” OR “RCT” OR “Systematic review” OR “meta-analysis”
	13 11 AND 12
PubMed	11 “Type-1 Diabetes mellitus” OR “T1DM”(MeSH Terms)1 OR “Teplizumab”(all fields) OR “anti-CD3 monoclonal antibody”(all fields)
	12 “Insulin”(MeSH Terms) OR “Glycated hemoglobin A1c”(all fields) OR “HbA1C”(all fields) OR “C-peptide”(all fields) OR “Adverse events” OR “Randomized controlled trials”(all fields) OR “RCT”(all fields) OR “systematic review” OR “meta-analysis”
	13 11 AND 12
Embase	“Type-1 Diabetes mellitus”/ exp2 OR “TIDM”/ exp OR “Teplizumab”/exp OR “anti-CD3 monoclonal antibody”/exp
	12 “Insulin”/ exp OR “Glycated hemoglobin A1c” / exp OR “HbA1C”/exp OR “C-peptide”/exp OR “Adverse events”/exp OR “Randomized controlled trials”/exp OR “RCT”/exp OR “systematic review”/ exp OR “meta-analysis”
	13 11 AND 12
Cochrane library	11 (Type-1 Diabetes mellitus): Ti, ab, kw3 OR (T1DM): Ti, ab, kw OR (Teplizumab): Ti, ab, kw OR (anti-CD3 monoclonal antibody): Ti, ab, kw OR (Cortisol): Ti, ab, kw (Word variations have been searched)
	12 (Insulin): Ti, ab, kw OR (Glycated hemoglobin A1c): Ti, ab, kw OR (HbA1C): Ti, ab, kw or (C-peptide): Ti, ab, kw or (Adverse events): Ti, ab, kw or (Randomized controlled trials): Ti, ab, kw or (systematic review): Ti, ab, kw or (meta-analysis): Ti, ab, kw (Word variations have been searched)
	13 11 AND 12

¹MeSH terms: Medical subject headings.

²exp: Explosion in emtree- searching of selected subject terms and related subjects.

³ti, ab, kw: Either title or abstract or keyword fields.

Table 2 Brief summary of the included studies

Ref.	Year of publication	Journal of publication	Country of study	Study setting	Study design	Total number of participants (n)	Diagnosis	Age of patients	Teplizumab group (n)	Control group (n)	Duration of study	Sex (M/F)	Primary outcomes
Herold et al[17]	2002	The New England Journal of Medicine	United States	HIC	RCT	24	Type-1 diabetes	7-30 years	12	12	1 year	18/6	Positive outcomes: Lower insulin uses and decrease in value of HbA1c, Adverse events
Hagopian et al[18]	2013	Diabetes	Sweden	HIC	RCT	410	Type-1 diabetes	8-35 years	311	99	2 years	295/115	Positive outcomes: Change in area under the curve for C-peptide, lower insulin uses and decrease in value of HbA1c, Adverse events
Herold et al[19]	2013	Diabetologia	United States	HIC	RCT	58	Type-1 diabetes	12-15 years	31	27	1 year	30/28	Positive outcomes: Change in area under the curve for C-peptide, and decrease in value of HbA1c, Adverse events
Herold et al[20]	2019	New England Journal of medicine	United States	HIC	RCT	76	Type-1 diabetes	12-22 years	44	32	2 years	36/40	Positive outcomes: Decrease in value of HbA1c, Adverse events
Herold et al[21]	2023	Diabetes care	United States	HIC	RCT	609	Type-1 diabetes	8-35 years	375	234	1 year	370/239	Positive outcomes: Change in area under the curve for C-peptide, and decrease in value of HbA1c, Adverse events
Perdigoto et al[22]	2019	Diabetologia	United States	HIC	RCT	43	Type-1 diabetes	8-30 years	31	12	2 years	26/17	Positive outcomes: Change in area under the curve for C-peptide, and decrease in value of HbA1c, Adverse events
Sherry et al[23]	2011	Lancet	United States	HIC	RCT	763	Type-1 diabetes	8-35 years	513	99	2 years	325/438	Positive outcomes: Lower insulin uses and decrease in value of HbA1c, Adverse events
Sims et al[24]	2021	Science Translation medicine	United States	HIC	RCT	76	Type-1 diabetes	8-39 years	44	32	2 years	40/36	Positive outcomes: Change in area under the curve for C-peptide and decrease in value of HbA1c, Adverse events

HbA1c: Glycated haemoglobin A1c; RCT: Randomized controlled trial; M: Male; F: Female; HIC: High income countries.

Table 3 Risk of bias assessment of included studies

	Herold et al[17]	Hagopian et al[18]	Herold et al[19]	Herold et al[20]	Herold et al[21]	Perdigoto et al[22]	Sherry et al[23]	Sims et al[24]
Did the study avoid inappropriate exclusions	Y	Y	Y	Y	Y	Y	Y	Y
Did all patients receive the same reference standard	Y	Y	Y	Y	Y	Y	Y	Y
Were all patients included in the analysis	N	N	N	N	N	N	N	N
Was the sample frame appropriate to address the target population	Y	Y	Y	Y	Y	Y	Y	Y
Were study participants sampled in an appropriate way	Y	Y	Y	Y	Y	Y	Y	Y
Were the study subjects and the setting described in detail	Y	Y	Y	Y	Y	Y	Y	Y
Were valid methods used for the identification of the condition	Y	Y	Y	Y	Y	Y	Y	Y
Was the condition measured in a standard, reliable way for all participants	Y	Y	Y	Y	Y	Y	Y	Y

Y: Yes; N: No.