Table 1.

PICOTS for the systematics literature review

Criterion	Description
Patient population	T2DM (adults, ≥ 18 years), uncontolled HbA1c (HbA1c > 7.0%), being managed with metformin
Interventions	Approved doses of the following oral therapies and their combinations (dose reported as once daily if not otherwise specified): Metformin + SGLT-2i (ertugliflozin 5 mg/15 mg, canagliflozin 100 mg/300 mg, dapagliflozin 5 mg/10 mg, empagliflozin 10 mg/25 mg) Metformin + DPP-4i (saxagliptin 2.5 mg/5 mg, linagliptin 5 mg, alogliptin 25 mg, sitagliptin 100 mg, vildagliptin 50 mg twice per day) Metformin + DPP-4i + SGLT-2i (DPP-4i: saxagliptin 2.5 mg/5 mg, linagliptin 5 mg, alogliptin, vildagliptin, sitagliptin 100 mg; SGLT-2i: ertugliflozin 5 mg/15 mg, canagliflozin 100 mg/300 mg, dapagliflozin 5 mg/10 mg, empagliflozin 10 mg/25 mg) Metformin + oral GLP-1 RA (semaglutide 7 mg/14 mg)
Comparators	Same as interventions, and metformin + placebo (dosing studies that only included metformin were excluded)
Outcomes	Continuous outcomes—Changes in HbA1c (%), weight (kg), SBP (mmHg), DBP (mmHg) Binary outcomes—HbA1c within target range (exploratory outcome: expected range defined as: HbA1c < 7.0%)
Time	No date restriction
Study design	RCT
Restrictions	Trial duration: Outcomes reported at 24 ± 2 weeks (trials longer than 24 weeks were reviewed to capture any interim reporting at the 24 to 26-week target timeframe) Language: English Country: any
Exclusions in addition to not meeting PICOTS criteria	Patients receiving insulin at study entry Insulin as a comparator treatment Non-human Type 1 diabetes Children (age < 18 years)

DBP diastolic blood pressure, DPP-4i dipeptidyl peptidase-4 inhibitor, GLP-1 RA glucagon-like peptide-1 receptor agonist, HbA1c glycated hemoglobin, RCT randomized clinical trial, SBP systolic blood pressure, SGLT-2i sodium–glucose co-transporter 2 inhibitor