Table 2.

Overview of the design and baseline patient characteristics from the PIONEER trial program

	Active-controlled trials				Active- and placebo-controlled trials		Placebo-controlled trials
	PIONEER 2 [47]	PIONEER 3 [48]	PIONEER 7 [52]	PIONEER 10 [55]	PIONEER 9 [54]	PIONEER 4 [49]	PIONEER 8 [53]	PIONEER 1 [46]	PIONEER 5 [50]	PIONEER 6 [51, 64]
Study duration	52 weeks	78 weeks	52 weeks	52 weeks	52 weeks	52 weeks	52 weeks	26 weeks	26 weeks	Event-driven
Patient population	Multinational; T2D	Multinational; T2D	Multinational; T2D	Japan; T2D	Japan; T2D	Multinational; T2D	Multinational; T2D	Multinational; T2D	Multinational; T2D and moderate renal impairment	Multinational; T2D and high CV risk
Number of patients	822a	1,864	504	458	243	711	731	703	324	3,183
Comparators	Oral sema 14 mg	Oral sema 3 mg	Oral sema flex	Oral sema 3 mg	Oral sema 3 mg	Oral sema 14 mg	Oral sema 3 mg	Oral sema 3 mg	Oral sema 14 mg	Oral sema 14 mg
	Empa 25 mg	Oral sema 7 mg	Sita 100 mg	Oral sema 7 mg	Oral sema 7 mg	Lira 1.8 mg	Oral sema 7 mg	Oral sema 7 mg	Placebo	Placebo
		Oral sema 14 mg		Oral sema 14 mg	Oral sema 14 mg	Placebo	Oral sema 14 mg	Oral sema 14 mg
		Sita 100 mg		Dula 0.75 mg	Lira 0.9 mg		Placebo	Placebo
					Placebo
Background medication	Met	Met ± SU	1–2 OADsb	1 OADc	Diet and exercised	Met ± SGLT2i	Ins ± met	Diet and exercise	Met ± SU, SU alone, or ins ± met	Standard of care
HbA1c inclusion criteria	7.0–10.5%	7.0–10.5%	7.5–9.5%	7.0–10.5%	6.5–9.5%	7.0–9.5%	7.0–9.5%	7.0–9.5%	7.0–9.5%	–
Primary endpoint	Change in HbA1c from baseline to week 26	Change in HbA1c from baseline to week 26	Achievement of HbA1c < 7.0% (53 mmol/mol) at week 52	Number of treatment-emergent AEs at week 57	Change in HbA1c from baseline to week 26	Change in HbA1c from baseline to week 26	Change in HbA1c from baseline to week 26	Change in HbA1c from baseline to week 26	Change in HbA1c from baseline to week 26	Time to first occurrence of MACEe
Key secondary endpoint(s)	Change in body weight from baseline to weeks 26 and 52	Change in body weight from baseline to weeks 26, 52, and 78	Change in body weight from baseline to week 52	Change in HbA1c and body weight at weeks 26 and 52	Change in body weight from baseline to weeks 26 and 52	Change in body weight from baseline to weeks 26 and 52	Change in body weight from baseline to weeks 26 and 52	Change in body weight from baseline to week 26	Change in body weight from baseline to week 26	Expanded composite outcomef
Baseline characteristics
Mean age, years	58	58	57	58	59	56	61	55	70	66
Mean HbA1c, % (mmol/mol)g	8.1 (65)	8.3 (67)	8.3 (67)	8.3 (68)	8.2 (66)	8.0 (64)	8.2 (66)	8.0 (63)	8.0 (64)	8.2 (66)
Mean duration of diabetes, years	7.4	8.6	8.8	9.4	7.6	7.6	15.0	3.5	14.0	14.9
Mean body weight, kg	91.6	91.2	88.6	72.1	71.1	94.0	85.9	88.1	90.8	90.9

Baseline characteristic data represent mean for total population

All trials shown here included a 2-week screening period and 5-week follow-up period (for those not continuing into the extension phase in PIONEER 7)

AE adverse event, CV cardiovascular, dula dulaglutide, empa empagliflozin, flex flexible dose adjustment, HbA_1c glycated hemoglobin, ins insulin, lira liraglutide, MACE major adverse cardiovascular event, met metformin, OAD oral antidiabetes drug, sema semaglutide, SGLT2i sodium-glucose co-transporter-2 inhibitor, sita sitagliptin, SU sulfonylurea, T2D type 2 diabetes

^aOne patient enrolled at two sites so analyses were based on 821 patients

^bIncluding metformin, SU, SGLT2i, or TZD

^cIncluding SU, glinide, TZD, alpha-glucosidase inhibitor, or SGLT2i

^dPatients could have been treated with oral glucose-lowering therapy but this was washed out prior to the trial

^eCV death, nonfatal myocardial infarction, or nonfatal stroke

^fThe expanded composite outcome consisted of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, unstable angina resulting in hospitalization, or heart failure resulting in hospitalization

^gmmol/mol values were converted from National Glycohemoglobin Standardization Program (%) values if not reported in the manuscript.