. 2022 Oct 18;25(1):18–35. doi: 10.1111/dom.14863

TABLE 2.

Efficacy results from the STEP 1‐5 and 8 trials ^a

	STEP 1 ³⁸		STEP 2 ³⁹			STEP 3 ⁴⁰		STEP 4 ⁴¹		STEP 5 ⁴²		STEP 8 ⁴³
	Weight management		Weight management in type 2 diabetes			Weight management with intensive behavioural therapy		Sustained weight management		Two‐year weight management		Semaglutide vs. liraglutide
	Semaglutide 2.4 mg (n = 1306)	Placebo (n = 655)	Semaglutide 2.4 mg (n = 404)	Semaglutide 1.0 mg (n = 403)	Placebo (n = 403)	Semaglutide 2.4 mg (n = 407)	Placebo (n = 204)	Semaglutide 2.4 mg (n = 535)	Placebo (n = 268)	Semaglutide 2.4 mg (n = 152)	Placebo (n = 152)	Semaglutide 2.4 mg (n = 126)	Liraglutide 3.0 mg (n = 127)	Placebo (n = 85) ^b
% weight change	−14.9	−2.4	−9.6	−7.0	−3.4	−16.0	−5.7	Baseline to week 20: −10.6; week 20‐68: −7.9; week 0‐68: −17.4	Week 20‐68: 6.9; week 0‐68: −5.0	−15.2	−2.6	−15.8	−6.4	−1.9
Treatment difference	−12.4		2.4 mg vs. 1.0 mg −2.7 2.4 mg vs. placebo −6.2			−10.3		−14.8		−12.6		Sema vs. lira −9.4
% of participants with weight reduction of: ^c
≥5%	86.4	31.5	68.8	57.1	28.5	86.6	47.6	88.7	47.6	77.1	34.4	87.2	58.1	29.5
≥10%	69.1	12.0	45.6	28.7	8.2	75.3	27.0	79.0	20.4	61.8	13.3	70.9	25.6	15.4
≥15%	50.5	4.9	25.8	13.7	3.2	55.8	13.2	63.7	9.2	52.1	7.0	55.6	12.0	6.4
≥20%	32.0	1.7	13.1	4.7	1.6	35.7	3.7	39.6	4.8	36.1	2.3	38.5	6.0	2.6
Change from baseline to end of treatment in:
Waist circumference change, cm	−13.54	−4.13	−9.4	−6.7	−4.5	−14.6	−6.3	−6.4	3.3	−14.4	−5.2	−13.2	−6.6	−2.0
Treatment difference	−9.42		2.4 mg vs. 1.0 mg –2.7 2.4 mg vs. placebo −4.9			−8.3		−9.7		−9.2		Sema vs. lira −6.6
Systolic blood pressure, mmHg	−6.16	−1.06	−3.9	−2.9	−0.5	−5.6	−1.6	0.5	4.4	−5.7	−1.6	−5.7	−2.9	3.2
Treatment difference	−5.10		2.4 mg vs. 1.0 mg −1.0 2.4 mg vs. placebo −3.4			−3.9		−3.9		−4.2		Sema vs. lira −2.8
Diastolic blood pressure, mmHg	−2.83	−0.42	−1.6	−0.6	−0.9	−3.0	−0.8	0.3	0.9	−4.4	−0.8	−5.0	−0.5	0.7
Treatment difference	−2.41		2.4 mg vs. 1.0 mg −0.9 2.4 mg vs. placebo −0.7			−2.2		−0.6		−3.7		Sema vs. lira −4.5
SF‐36 physical functioning score	2.21	0.41	2.5	2.4	1.0	2.4	1.6	1.0	−1.5	NA	NA	NA	NA	NA
Treatment difference	1.80		2.4 mg vs. 1.0 mg 0.1 2.4 mg vs. placebo 1.5			0.8		2.5		–		–
IWQOL‐Lite‐CT physical function score	14.67	5.25	10.1	8.7	5.3	NA	NA	NA	NA	NA	NA	NA	NA	NA
Treatment difference	9.43		2.4 mg vs. 1.0 mg 1.4 2.4 mg vs. placebo 4.8			–		–		–		–
Body weight, kg	−15.3	−2.6	−9.7	−6.9	−3.5	−16.8	−6.2	−7.1	6.1	−16.1	−3.2	−15.3	−6.8	−1.6
Treatment difference	−12.7		2.4 mg vs. 1.0 mg −2.7 2.4 mg vs. placebo −6.1			−10.6		−13.2		−12.9		Sema vs. lira −8.5
BMI, kg/m²	−5.54	−0.92	−3.5	−2.5	−1.3	−6.0	−2.2	−2.6	2.2	−5.9	−1.6	NA	NA	NA
Treatment difference	−4.61		2.4 mg vs. 1.0 mg −1.0 2.4 mg vs. placebo −2.3			−3.8		−4.7		−12.6		−
HbA1c, %	−0.45	−0.15	−1.6	−1.5	−0.4	−0.51	−0.27	−0.1	0.1	−0.4	−0.1	−0.2	−0.1	0.1
Treatment difference	−0.29		2.4 mg vs. 1.0 mg −0.2 2.4 mg vs. placebo −1.2			−0.24		−0.2		−0.3		Sema vs. lira −0.2
Fasting plasma glucose, mg/dl	−8.35	−0.48	−38.0	−32.2	−1.4^c	−6.73	−0.65	−0.8	6.7	−7.6	1.7	−8.3	−4.3	3.3
Treatment difference	−7.87		2.4 mg vs. 1.0 mg −5.7 2.4 mg vs. placebo −36.6			−6.09		−7.5		−9.3		Sema vs. lira −3.9
Lipid levels, % change ^d
Total cholesterol	−3.0	0	−1.0	−2.0	−1.0	−3.8	2.1	5	11	−3.3	1.4	−7.1	−0.1	−3.3
Treatment difference	−3.0		2.4 mg vs. 1.0 mg 1.0^l 2.4 mg vs. placebo −1.0			−5.8		−6		−4.6		Sema vs. lira −7.0
HDL cholesterol	5.0	1.0	7.0	5.0	4.0	6.5	5.0	18	18	9.6	8.1	−0.3	1.9	−0.9
Treatment difference	4.0		2.4 mg vs. 1.0 mg 2.0 2.4 mg vs. placebo 3.0			1.5		0		1.3		Sema vs. lira −2.2
LDL cholesterol	−3.0	1.0	0	−1.0	0	−4.7	2.6	1	8	−6.1	−2.7	−6.5	0.9	−1.1
Treatment difference	−4.0		2.4 mg vs. 1.0 mg 1.0 2.4 mg vs. placebo 0			−7.1		−6		−3.4		Sema vs. lira −7.3
VLDL cholesterol	−22.0	−7.0	−21.0	−17.0	−10.0	−22.5	−6.6	−6	15	−18.9	3.3	−20.7	−10.9	−4.1
Treatment difference	−16.0		2.4 mg vs. 1.0 mg −5.0 2.4 mg vs. placebo −12.0			−17.0		−18		−21.5		Sema vs. lira −11.0
Free fatty acids	−17.0	−7.0	−16.0	−14.0	−1.0	−11.9	4.0	−18	−14	0.3	7.0	−12.6	−8.8	2.6
Treatment difference	−11.0		2.4 mg vs. 1.0 mg −3.0 2.4 mg vs. placebo −16.0			−15.3		−5		−6.2		Sema vs. lira −4.2
Triglycerides	−22.0	−7.0	−22.0	−17.0	−9.0	−22.5	−6.5	−6	15	−19.0	−3.7	−20.7	−11.0	−3.2
Treatment difference	−16.0		2.4 mg vs. 1.0 mg −6.0 2.4 mg vs. placebo −14.0			−6.5		−18		−21.9		Sema vs. lira −11.0

Abbreviations: BMI, body mass index; HbA1c, glycated haemoglobin; HDL, high‐density lipoprotein; IWQOL‐Lite‐CT, impact of weight on quality of life‐lite clinical trials version questionnaire; LDL, low‐density lipoprotein; NA, not available; SF‐36, short form‐36 version 2 health survey, acute version; VLDL, very low‐density lipoprotein.

^{^a}

Results are estimated data for the treatment policy estimand (effects assessed regardless of treatment discontinuation or rescue intervention); data and treatment differences are reported for the randomized period [i.e. baseline (week 20 in STEP 4) to week 68 for STEP 1, 2, 3, 4 and 8, and from baseline to week 104 for STEP 5].

^{^b}

Pooled placebo data.

^{^c}

Observed percentages of participants who had body weight reductions of ≥5%, ≥10%, ≥15% and ≥20% from baseline to week 68 (week 104 for STEP 5) during the in‐trial observation period, based on the number of participants for whom data were available at the week 68 visit (week 104 for STEP 5).

^{^d}

For STEP 1 and 2, lipid parameters were initially analysed on a log scale as estimated ratio of end of treatment value to baseline. For interpretation, these data are expressed as relative percentage change and were calculated using the formula (estimated ratio − 1) × 100.