parallel randomized trial

NCT05514535

Efficacy and Safety of Once-weekly Semaglutide S.C. 2.0 mg as Add-on to Dose-reduced Insulin Glargine vs Titrated Insulin Glargine in Participants With Type 2 Diabetes and Overweight

Type 2 diabetes (adults)NCT05514535S001161

Design

Randomized: 573
Start year: 2022
Treatment: 40 weeks, follow-up 45 weeks
Countries: multinational (113 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: adults with T2D, BMI 25 or more, HbA1c 7 to 10 percent, basal insulin up to 40 U/day plus metformin with or without SGLT2i

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 2.0 mg subcutaneous once weekly Semaglutide 2.0 mg plus reduced insulin glargine	insulin glargine U100 plus metformin with or without SGLT2i; lifestyle: not reported	288	288
A2	Insulin glargine Insulin glargine titrated	metformin with or without SGLT2i; lifestyle: not reported	285	285

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Semaglutide 2.0 mg subcutaneous once weekly A1	Insulin glargine A2
age	mean (years)	61.7	60.5
age	sd (years)	9.7	10.3
asian	n	33	22
asian	percent	11.5	7.7
black	n	10	9
black	percent	3.5	3.2
bmi	mean (kg/m2)	32.5	33.4
bmi	sd (kg/m2)	5.3	5.9
diabetes duration	mean (years)	12.4	12.4
diabetes duration	sd (years)	7.7	7.4
egfr	mean (mL/min/1.73 m2)	86.8	88.1
female	n	124	129
female	percent	43.1	45.3
hba1c	mean (percent)	7.9	7.9
hba1c	sd (percent)	0.7	0.6
hispanic	n	27	31
hispanic	percent	9.4	10.9
insulin dose	median (U/day)	26.0	28.0
other race multiple	n	1	0
other race multiple	percent	0.3
other race native hawaiian pacific islander	n	1	0
other race native hawaiian pacific islander	percent	0.3
sbp	mean (mmHg)	132	133
sbp	sd (mmHg)	14	14
sglt2i use	n	138	137
sglt2i use	percent	47.9	48.1
weight	mean (kg)	92.6	95.2
weight	sd (kg)	17.9	20.6
white	n	243	253
white	percent	84.4	88.8

Analyses this trial contributes to

Results

69 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (5 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-1.37 percent	0.84		276	not stated; full analysis; registry:outcomes
40	A1	change	-1.4 percent			288	treatment policy; full analysis; R0015842:Results
40	A1 vs A2	md	-0.74 percent		-0.90 to -0.59		treatment policy; full analysis; R0015842:Results
40	A2	change	-0.65 percent	0.92		272	not stated; full analysis; registry:outcomes
40	A2	change	-0.6 percent			285	treatment policy; full analysis; R0015842:Results

Body weight change in kilograms (diabetes) (5 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1 vs A2	md	-8.5 kg		-9.5 to -7.4		treatment policy; full analysis; R0015842:Results
40	A1	change	-7.97 kg	5.62		282	not stated; full analysis; registry:outcomes
40	A1	change	-8.0 kg			288	treatment policy; full analysis; R0015842:Results
40	A2	change	0.5 kg			285	treatment policy; full analysis; R0015842:Results
40	A2	change	0.39 kg	4.08		275	not stated; full analysis; registry:outcomes

HbA1c below 7 percent (4 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
40	A1	responders	77.6	288	treatment policy; full analysis; R0015842:Results
40	A1	responders		224 / 285	not stated; full analysis; registry:outcomes
40	A2	responders	39.0	285	treatment policy; full analysis; R0015842:Results
40	A2	responders		111 / 281	not stated; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	14 / 288	not stated; safety; R0015842:Table 2
A1	events	4 / 288	not stated; safety; R0015842:Table 2
A2	events	21 / 284	not stated; safety; R0015842:Table 2
A2	events	11 / 284	not stated; safety; R0015842:Table 2

Level 2 or 3 hypoglycemia (episode rate) (9 lines; O04B)

Arm	Statistic	Estimate	SE or SD	95% CI	Detail
A1	rate	0.06	0.02		while on treatment; safety; R0015842:Supplement Table S3
A1 vs A2	rate ratio	0.48		0.22 to 1.03	while on treatment; safety; R0015842:Supplement Table S3
A1	rate	0.08	0.02		while on treatment; safety; R0015842:Supplement Table S3
A1	rate	0.01	0.01		while on treatment; safety; R0015842:Supplement Table S3
A1 vs A2	rate ratio	0.22		0.05 to 0.93	while on treatment; safety; R0015842:Supplement Table S3
A1 vs A2	rate ratio	0.45		0.23 to 0.87	while on treatment; safety; R0015842:Results
A2	rate	0.13	0.03		while on treatment; safety; R0015842:Supplement Table S3
A2	rate	0.19	0.04		while on treatment; safety; R0015842:Supplement Table S3
A2	rate	0.05	0.93		while on treatment; safety; R0015842:Supplement Table S3

Percent body weight change (1 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1 vs A2	md	-9.3 percent		-10.4 to -8.2		treatment policy; full analysis; R0015842:Results

Weight loss of 5 percent or more (2 lines; O11A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	responders	73.2			288	treatment policy; full analysis; R0015842:Results
40	A2	responders	9.1			285	treatment policy; full analysis; R0015842:Results

Weight loss of 10 percent or more (2 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	responders	38.0			288	treatment policy; full analysis; R0015842:Results
40	A2	responders	1.6			285	treatment policy; full analysis; R0015842:Results

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 288	not stated; safety; R0015842:Table 2
	A2	events				1 / 284	not stated; safety; R0015842:Table 2

SF-36 physical component summary change (2 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	3.18 points	7.47		288	not stated; full analysis; registry:outcomes
40	A2	change	0.12 points	6.67		285	not stated; full analysis; registry:outcomes

Health related quality of life total score (any instrument) (7 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	final	14.6 points				treatment policy; full analysis; R0015842:Results
40	A1 vs A2	md	2.6 points		1.6 to 3.5		treatment policy; full analysis; R0015842:Results
40	A1	change	4.56 points	7.04		265	not stated; full analysis; registry:outcomes
40	A1	final	14.69 points	4.65		270	not stated; full analysis; registry:outcomes
40	A2	final	12.1 points				treatment policy; full analysis; R0015842:Results
40	A2	change	2.17 points	7.04		262	not stated; full analysis; registry:outcomes
40	A2	final	12.11 points	6.84		262	not stated; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 288	not stated; safety; R0015842:Table 2
	A2	events				15 / 284	not stated; safety; R0015842:Table 2

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 288	not stated; safety; R0015842:Table 2
	A2	events				1 / 284	not stated; safety; R0015842:Table 2

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				53 / 288	not stated; safety; R0015842:Table 2
	A2	events				2 / 284	not stated; safety; R0015842:Table 2

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				28 / 288	not stated; safety; R0015842:Table 2
	A2	events				1 / 284	not stated; safety; R0015842:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				39 / 288	not stated; safety; R0015842:Table 2
	A2	events				12 / 284	not stated; safety; R0015842:Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				23 / 288	not stated; safety; registry:adverse_events
	A2	events				0 / 284	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				4 / 288	not stated; safety; R0015842:Table 2
	A2	events				0 / 284	not stated; safety; R0015842:Table 2

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 288	not stated; safety; R0015842:Table 2
	A2	events				2 / 284	not stated; safety; R0015842:Table 2

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 288	not stated; safety; acute pancreatitis; R0015842:Table 2
A1	events	1 / 288	not stated; safety; pancreatitis; R0015842:Table 2
A2	events	1 / 284	not stated; safety; acute pancreatitis; R0015842:Table 2
A2	events	0 / 284	not stated; safety; pancreatitis; R0015842:Table 2

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 288	not stated; safety; thyroid cancer; registry:adverse_events
	A2	events				1 / 284	not stated; safety; thyroid cancer; registry:adverse_events

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 288	not stated; safety; diabetic retinopathy; R0015842:Table 2
	A2	events				11 / 284	not stated; safety; diabetic retinopathy; R0015842:Table 2

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 288	not stated; safety; pancreatic carcinoma; registry:adverse_events
	A2	events				0 / 284	not stated; safety; pancreatic carcinoma; registry:adverse_events