parallel randomized trial

NCT02846233

Is the Stepping-down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?

Type 2 diabetes (adults)NCT02846233S000236

Design

Randomized: 22
Start year: 2016
Treatment: 16 weeks, follow-up 16 weeks
Countries: United States
Sponsor: University of California, San Francisco (non industry)
Eligibility: age over 21; BMI 30 or more; HbA1c above 8 percent; eGFR above 45; basal plus prandial or premixed insulin

Conduct and analysis

Blinding: open label
Sequence generation: computer
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: completers
Missing data: none

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Dulaglutide flexible dose injection once weekly Step down: basal insulin, metformin, empagliflozin and dulaglutide	empagliflozin 10 or 12.5 mg daily up to 25 mg; basal insulin from 80 percent of home dose, self titrated; metformin; prandial insulin stopped; lifestyle: not reported	12	10
A2	Basal bolus insulin Continued multiple daily insulin injections	metformin; usual care by primary care provider; no SGLT2 inhibitor or GLP-1 receptor agonist; lifestyle: not reported	10	8

Baseline characteristics

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

Characteristic	Statistic	Dulaglutide flexible dose injection once weekly A1	Basal bolus insulin A2
age	mean (years)	51.8	55.62
age	sd (years)	11.14	11.78
bmi	mean (kg/m2)	36.27	36.73
bmi	sd (kg/m2)	4.52	4.83
diabetes duration	mean (years)	13.4	15.75
diabetes duration	sd (years)	7.99	6.88
egfr	mean (mL/min/1.73 m2)	85.4	85.5
egfr	sd (mL/min/1.73 m2)	8.53	6.63
female	n	4	5
hba1c	mean (percent)	9.69	10.36
hba1c	sd (percent)	1.067	0.877
hispanic	n	8	5
hispanic	percent	80	62.5
insulin dose	mean (units)	107.7	97.6
insulin dose	sd (units)	64.14	54.0
metformin use	n	10	8
metformin use	percent	100	100
sbp	mean (mmHg)	127.2	121.5
sbp	sd (mmHg)	17.25	16.87
weight	mean (lb)	212.7	226
weight	sd (lb)	39.06	52.82
white	n	2	3
white	percent	20	37.5

Analyses this trial contributes to

Results

43 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
16	A1	change	-2.38 percent		-2.93 to -1.83	10	not stated; completers; R0028441:Table 3
16	A1 vs A2	md	-2.23 percent				not stated; completers; R0028441:Table 4
16	A1	final	7.31 percent	0.81		10	not stated; completers; R0028441:Table 4
16	A2	change	-0.83 percent		-2.05 to 0.40	8	not stated; completers; R0028441:Table 2
16	A2	final	9.54 percent	1.11		8	not stated; completers; R0028441:Table 4

Body weight change in kilograms (diabetes) (6 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	-16.38 lb		-25.63 to -7.13	10	not stated; completers; R0028441:Table 3
16	A1	final	196.3 lb	36.53		10	not stated; completers; R0028441:Table 4
16	A1 vs A2	md	-28.7 lb				not stated; completers; R0028441:Table 4
16	A2	final	225 lb	47.98		8	not stated; completers; R0028441:Table 4
16	A2	change	-0.98 lb		-9.25 to 7.3	8	not stated; completers; R0028441:Table 2
16	A2	change	-0.1 lb		-1.34 to 1.14	8	not stated; completers; registry:outcomes

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	responders				4 / 10	not stated; completers; R0028441:Table 4
16	A2	responders				0 / 8	not stated; completers; R0028441:Table 4

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 12	not stated; randomized; R0028441:Table 5
A1	events	1 / 12	not stated; randomized; R0028441:Table 5
A2	events	3 / 10	not stated; randomized; R0028441:Table 5
A2	events	1 / 10	not stated; randomized; R0028441:Table 5

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	-16 mmHg		-33.37 to 1.37	10	not stated; completers; R0028441:Table 3
16	A1	final	111.2 mmHg	16.01		10	not stated; completers; R0028441:Table 4
16	A1 vs A2	md	-25.3 mmHg				not stated; completers; R0028441:Table 4
16	A2	final	136.5 mmHg	20.04		8	not stated; completers; R0028441:Table 4
16	A2	change	15 mmHg		2.56 to 27.44	8	not stated; completers; R0028441:Table 2

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 12	not stated; randomized; registry:adverse_events
	A2	events				0 / 10	not stated; randomized; registry:adverse_events

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	45.3 points		28.19 to 62.41	10	not stated; completers; R0028441:Table 3
16	A1	final	89 points	8.59		10	not stated; completers; R0028441:Table 4
16	A1 vs A2	md	32.5 points				not stated; completers; R0028441:Table 4
16	A2	change	4.63 points		-0.83 to 10.08	8	not stated; completers; R0028441:Table 2
16	A2	final	56.5 points	15.45		8	not stated; completers; R0028441:Table 4

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 12	not stated; randomized; registry:adverse_events
	A2	events				0 / 10	not stated; randomized; registry:adverse_events

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 12	not stated; randomized; R0028441:Table 5
	A2	events				0 / 10	not stated; randomized; R0028441:Table 5

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 12	not stated; randomized; R0028441:Table 5
	A2	events				0 / 10	not stated; randomized; R0028441:Table 5

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 12	not stated; randomized; R0028441:Table 5
	A2	events				0 / 10	not stated; randomized; R0028441:Table 5

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 12	not stated; randomized; R0028441:Table 5
	A2	events				0 / 10	not stated; randomized; R0028441:Table 5

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 12	not stated; randomized; R0028441:Table 5
	A2	events				0 / 10	not stated; randomized; R0028441:Table 5

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 12	not stated; randomized; R0028441:Table 5
	A2	events				0 / 10	not stated; randomized; R0028441:Table 5