parallel randomized trial

COMBINE 1

A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Insulin Icodec, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin.

Type 2 diabetes (adults)NCT05352815S000458

Design

Randomized: 1,291
Start year: 2022
Treatment: 52 weeks, follow-up 57 weeks
Countries: multinational (192 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: adults 18+; HbA1c 7.0-10.0%; BMI 40 or less; basal insulin 20-80 U/day; eGFR 30 or more

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Insulin icodec and semaglutide (IcoSema) subcutaneous once weekly titrated IcoSema	prior non insulin drugs continued except SU, glinides, DPP4i; prior basal insulin stopped; lifestyle: not reported	646	646
A2	Insulin icodec Insulin icodec	prior non insulin drugs continued except SU, glinides, DPP4i; lifestyle: not reported	645	645

Baseline characteristics

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

Characteristic	Statistic	Insulin icodec and semaglutide (IcoSema) subcutaneous once weekly titrated A1	Insulin icodec A2
age	mean (years)	60.5	60.7
age	sd (years)	10.5	10.2
asian	n	216	204
black	n	19	25
egfr: 60-<90	n	288	280
egfr: <60	n	74	76
egfr: >=90	n	284	289
female	n	246	246
hispanic	n	101	110
other race american indian alaska native	n	5	1
other race multiple	n	2	4
other race native hawaiian pacific islander	n	0	1
white	n	404	410

Analyses this trial contributes to

Results

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

HbA1c change (3 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	-0.66 percent		-0.76 to -0.57		not stated; full analysis; registry:outcomes
52	A1	change	-1.60 percent	0.99		598	not stated; full analysis; registry:outcomes
52	A2	change	-0.90 percent	1.01		605	not stated; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (2 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-3.71 kg	4.87		606	not stated; full analysis; registry:outcomes
52	A2	change	1.96 kg	4.76		610	not stated; full analysis; registry:outcomes

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 644	not stated; safety; registry:adverse_events
	A2	events				1 / 644	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				2 / 646	not stated; randomized; registry:adverse_events
	A2	events				3 / 645	not stated; randomized; registry:adverse_events

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				59 / 644	not stated; safety; registry:adverse_events
	A2	events				69 / 644	not stated; safety; registry:adverse_events

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	153 / 644	not stated; safety; registry:adverse_events
A1	events	0 / 644	not stated; safety; registry:adverse_events
A2	events	24 / 644	not stated; safety; registry:adverse_events
A2	events	1 / 644	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	68 / 644	not stated; safety; registry:adverse_events
A1	events	0 / 644	not stated; safety; registry:adverse_events
A2	events	1 / 644	not stated; safety; registry:adverse_events
A2	events	17 / 644	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 644	not stated; safety; registry:adverse_events
A1	events	102 / 644	not stated; safety; registry:adverse_events
A2	events	46 / 644	not stated; safety; registry:adverse_events
A2	events	1 / 644	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				39 / 644	not stated; safety; registry:adverse_events
	A2	events				8 / 644	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 644	not stated; safety; Cholecystitis acute; registry:adverse_events
A1	events	0 / 644	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	2 / 644	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	2 / 644	not stated; safety; Cholecystitis acute; registry:adverse_events

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				41 / 644	not stated; safety; Diabetic retinopathy; registry:adverse_events
	A2	events				35 / 644	not stated; safety; Diabetic retinopathy; registry:adverse_events

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 644	not stated; safety; Diabetic gastroparesis; registry:adverse_events
	A2	events				0 / 644	not stated; safety; Diabetic gastroparesis; registry:adverse_events

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 644	not stated; safety; Small intestinal obstruction; registry:adverse_events
	A2	events				1 / 644	not stated; safety; Small intestinal obstruction; registry:adverse_events

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 644	not stated; safety; Pancreatic carcinoma; registry:adverse_events
	A2	events				2 / 644	not stated; safety; Pancreatic carcinoma; registry:adverse_events