parallel randomized trial

NCT03596450

Long Term Comparative Effectiveness of Once Weekly Semaglutide Versus Standard of Care in a Real World Adult US Population With Type 2 Diabetes - a Randomized Pragmatic Clinical Trial

Type 2 diabetes (adults)NCT03596450S000545

Design

Randomized: 1,278
Start year: 2018
Treatment: 104.36 weeks, follow-up 104.36 weeks
Countries: United States (138 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: adults with type 2 diabetes on metformin, later up to 2 oral drugs, needing intensification

Conduct and analysis

Blinding: open label
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: no
Primary estimand: treatment policy
Analysis population: randomized
Missing data: multiple imputation by arm and on or off drug status

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide flexible dose injection once weekly Semaglutide once weekly, physician dosed	up to 2 oral glucose lowering drugs including metformin; lifestyle: not reported	644	644
A2	Standard care or no added treatment Alternative treatment chosen by physician	up to 2 oral glucose lowering drugs including metformin; lifestyle: not reported	634	634

Baseline characteristics

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

Characteristic	Statistic	Semaglutide flexible dose injection once weekly A1	Standard care or no added treatment A2
age	mean (years)	57.47	57.24
age	sd (years)	11.305	10.982
black	n	90	99
female	n	309	276
hispanic	n	57	57
other race american indian alaska native asian	n	16	27
other race native hawaiian pacific islander	n	3	2
other race other	n	17	19
white	n	517	487

Analyses this trial contributes to

Results

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

HbA1c change (10 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52.18	A1	change	-1.35 percent				treatment policy; randomized; R0015592:Results
52.18	A1	change	-1.46 percent	1.67		430	treatment policy; completers; R0015592:Table 1
52.18	A1 vs A2	md	-0.20 percent		-0.39 to 0.00		treatment policy; randomized; R0015592:Results
52.18	A2	change	-1.14 percent	1.71		461	treatment policy; completers; R0015592:Table 1
52.18	A2	change	-1.16 percent				treatment policy; randomized; R0015592:Results
104.36	A1	change	-1.45 percent	1.72		374	treatment policy; completers; R0015592:Table 1
104.36	A1 vs A2	md	-0.31 percent		-0.57 to -0.05		treatment policy; randomized; R0015592:Results
104.36	A1	change	-1.27 percent				treatment policy; randomized; R0015592:Results
104.36	A2	change	-0.98 percent	1.77		373	treatment policy; completers; R0015592:Table 1
104.36	A2	change	-0.96 percent				treatment policy; randomized; R0015592:Results

Body weight change in kilograms (diabetes) (4 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
52.18	A1	change	-9.8 lb	21.15	458	treatment policy; completers; registry:outcomes
52.18	A2	change	-5.4 lb	20.70	461	treatment policy; completers; registry:outcomes
104.36	A1	change	-11.1 lb	24.65	389	treatment policy; completers; registry:outcomes
104.36	A2	change	-6.8 lb	18.54	386	treatment policy; completers; registry:outcomes

HbA1c below 7 percent (10 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52.18	A1	responders	53.1			treatment policy; randomized; R0015592:Results
52.18	A1	responders			244 / 430	treatment policy; completers; R0015592:Table 1
52.18	A1 vs A2	or	1.36	1.03 to 1.79		treatment policy; randomized; R0015592:Results
52.18	A2	responders			226 / 462	treatment policy; completers; R0015592:Table 1
52.18	A2	responders	45.5			treatment policy; randomized; R0015592:Results
104.36	A1 vs A2	or	1.56	1.13 to 2.16		treatment policy; randomized; R0015592:Results
104.36	A1	responders	49.9			treatment policy; randomized; R0015592:Results
104.36	A1	responders			209 / 374	treatment policy; completers; R0015592:Table 1
104.36	A2	responders			162 / 374	treatment policy; completers; R0015592:Table 1
104.36	A2	responders	38.9			treatment policy; randomized; R0015592:Results

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 644	not stated; randomized; registry:outcomes
A1	events	1 / 644	not stated; randomized; registry:outcomes
A2	events	0 / 634	not stated; randomized; registry:outcomes
A2	events	1 / 634	not stated; randomized; registry:outcomes

Systolic blood pressure change (4 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
52.18	A1	change	-2.3 mmHg	16.40	456	treatment policy; completers; registry:outcomes
52.18	A2	change	-1.8 mmHg	16.34	457	treatment policy; completers; registry:outcomes
104.36	A1	change	-3.0 mmHg	17.03	388	treatment policy; completers; registry:outcomes
104.36	A2	change	-2.8 mmHg	16.91	386	treatment policy; completers; registry:outcomes

Percent body weight change (10 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52.18	A1 vs A2	md	-1.65 percent		-2.92 to -0.39		treatment policy; randomized; R0015592:Results
52.18	A1	percent change	-3.57 percent				treatment policy; randomized; R0015592:Results
52.18	A1	percent change	-3.93 percent	11.092		458	treatment policy; completers; registry:outcomes
52.18	A2	percent change	-1.91 percent				treatment policy; randomized; R0015592:Results
52.18	A2	percent change	-2.02 percent	8.924		461	treatment policy; completers; registry:outcomes
104.36	A1 vs A2	md	-1.48 percent		-3.62 to 0.66		treatment policy; randomized; R0015592:Results
104.36	A1	percent change	-4.47 percent	12.204		389	treatment policy; completers; registry:outcomes
104.36	A1	percent change	-3.84 percent				treatment policy; randomized; R0015592:Results
104.36	A2	percent change	-2.68 percent	7.988		386	treatment policy; completers; registry:outcomes
104.36	A2	percent change	-2.36 percent				treatment policy; randomized; R0015592:Results

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 634	not stated; safety; registry:adverse_events
	A2	events				1 / 621	not stated; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 634	not stated; safety; registry:adverse_events
	A2	events				9 / 621	not stated; safety; registry:adverse_events

Hospitalization for heart failure (6 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	1 / 634	not stated; safety; cardiac failure acute; registry:adverse_events
A1	events	0 / 634	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events	0 / 634	not stated; safety; cardiac failure; registry:adverse_events
A2	events	1 / 621	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	1 / 621	not stated; safety; cardiac failure; registry:adverse_events
A2	events	1 / 621	not stated; safety; cardiac failure acute; registry:adverse_events

SF-36 physical component summary change (4 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
52.18	A1	change	2.8 points	8.20	439	treatment policy; completers; registry:outcomes
52.18	A2	change	2.3 points	7.60	449	treatment policy; completers; registry:outcomes
104.36	A1	change	2.6 points	8.68	383	treatment policy; completers; registry:outcomes
104.36	A2	change	2.4 points	7.99	376	treatment policy; completers; registry:outcomes

Health related quality of life total score (any instrument) (5 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52.18	A1	final	13.5 points	5.28		447	treatment policy; completers; registry:outcomes
52.18	A2	final	12.8 points	5.82		460	treatment policy; completers; registry:outcomes
104.36	A1 vs A2	md	0.95 points		0.09 to 1.81		treatment policy; completers; R0015592:Results
104.36	A1	final	13.2 points	6.24		388	treatment policy; completers; registry:outcomes
104.36	A2	final	12.2 points	5.87		380	treatment policy; completers; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				38 / 634	not stated; safety; registry:adverse_events
	A2	events				39 / 621	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		14 / 644	not stated; randomized; registry:flow
A1	events	6.6		not stated; safety; R0015592:Results
A2	events		7 / 634	not stated; randomized; registry:flow
A2	events	4.7		not stated; safety; R0015592:Results

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 634	not stated; safety; registry:adverse_events
	A2	events				0 / 621	not stated; safety; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 634	not stated; safety; pancreatitis acute; registry:adverse_events
A1	events	0 / 634	not stated; safety; pancreatitis; registry:adverse_events
A2	events	0 / 621	not stated; safety; pancreatitis acute; registry:adverse_events
A2	events	1 / 621	not stated; safety; pancreatitis; registry:adverse_events

Pancreatic cancer (6 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	1 / 634	not stated; safety; acinar cell carcinoma of pancreas; registry:adverse_events
A1	events	1 / 634	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A1	events	1 / 634	not stated; safety; pancreatic carcinoma; registry:adverse_events
A2	events	0 / 621	not stated; safety; acinar cell carcinoma of pancreas; registry:adverse_events
A2	events	0 / 621	not stated; safety; pancreatic carcinoma; registry:adverse_events
A2	events	0 / 621	not stated; safety; adenocarcinoma pancreas; registry:adverse_events