Trial Outcomes & Findings for Dapagliflozin As Additional Treatment To Liraglutide And Insulin In Patients With Type 1 Diabetes (NCT NCT02518945)

Results Overview

T1D. Conservatively estimating a difference in mean HbA1c (the primary end point) of 0.5% before and after the treatment, and a sample size of 30 (2:1 drug to placebo ratio) should provide adequate power (.8) to detect a significant difference (.05) provided the standard deviation of the residuals in not greater than 0.4%. The sample size includes an additional 20% to account for the potential dropout. Changes in these end points were calculated by averaging the differences in weekly average values from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

26 participants

Primary outcome timeframe

12 weeks

Results posted on

2024-01-24

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Overall Study STARTED	9	17
Overall Study COMPLETED	9	17
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.	Total n=26 Participants Total of all reporting groups
Age, Continuous	52 years STANDARD_DEVIATION 3 • n=9 Participants	55 years STANDARD_DEVIATION 3 • n=17 Participants	53 years STANDARD_DEVIATION 3 • n=26 Participants
Sex: Female, Male Female	6 Participants n=9 Participants	10 Participants n=17 Participants	16 Participants n=26 Participants
Sex: Female, Male Male	3 Participants n=9 Participants	7 Participants n=17 Participants	10 Participants n=26 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
HbA1c %	7.4 % STANDARD_DEVIATION 0.2 • n=9 Participants	7.8 % STANDARD_DEVIATION 0.2 • n=17 Participants	7.6 % STANDARD_DEVIATION 0.2 • n=26 Participants
Average glucose	9.32 mmol/L STANDARD_DEVIATION 0.49 • n=9 Participants	9.16 mmol/L STANDARD_DEVIATION 0.38 • n=17 Participants	9.24 mmol/L STANDARD_DEVIATION 0.41 • n=26 Participants

PRIMARY outcome

Timeframe: 12 weeks

T1D. Conservatively estimating a difference in mean HbA1c (the primary end point) of 0.5% before and after the treatment, and a sample size of 30 (2:1 drug to placebo ratio) should provide adequate power (.8) to detect a significant difference (.05) provided the standard deviation of the residuals in not greater than 0.4%. The sample size includes an additional 20% to account for the potential dropout. Changes in these end points were calculated by averaging the differences in weekly average values from baseline.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Absolute Change After 12 Weeks From Baseline in Mean HbA1c With Addition of Dapagliflozin Compared to Placebo.	0 % HbA1c Standard Error 0.2	-0.66 % HbA1c Standard Error 0.1

SECONDARY outcome

Timeframe: 12 weeks

Comparison of the change in time spent at normal glucose concentrations between 70-180mg/dl after treatment with 12 weeks of dapagliflozin in addition to liraglutide and insulin.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Change in Time Spent at Normal Glucose Concentrations Between 70-160mg/dl	-1.4 percentage of time Standard Error 1.0	10 percentage of time Standard Error 4

SECONDARY outcome

Timeframe: 12 weeks.

Comparison of change in 24-hour urine glucose excretion after 12 weeks of treatment of dapagliflozin in addition to liraglutide and insulin compared to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Change in 24-hour Urine Glucose Excretion.	2.1 gram/day Standard Error 1.1	66.9 gram/day Standard Error 4.7

SECONDARY outcome

Timeframe: 12 weeks

Comparison of the change from baseline in total daily insulin requirements in units per kilogram after treatment 12 weeks of dapagliflozin or placebo in addition to liraglutide and insulin.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Change in Total Daily Insulin Requirements	-0.1 Units/Kg Standard Error 2.4	-3.5 Units/Kg Standard Error 1.9

SECONDARY outcome

Timeframe: 12 weeks

Comparison of change from baseline in Body weight after 12 weeks treatment with dapagliflozin or placebo in addition to liraglutide and insulin.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Change in Body Weight	0.7 Kg Standard Error 1.5	-1.9 Kg Standard Error 0.5

SECONDARY outcome

Timeframe: 12 weeks

Comparison of Systolic blood pressure in mm Hg before and after 12 weeks treatment with dapagliflozin in addition to liraglutide and insulin.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Change in Systolic Blood Pressure Before and After Treatment	-2 mmHg Standard Error 3	-12 mmHg Standard Error 4

SECONDARY outcome

Timeframe: 12 weeks

change from baseline in blood ketone bodies (measured as beta-hydroxybutyrates) after 12 weeks treatment with dapagliflozin or placebo in addition to liraglutide and insulin.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 Participants 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Change in Blood Ketone Bodies	-0.03 mM Standard Error 0.06	0.20 mM Standard Error 0.09

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Active Drugs

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=9 participants at risk 12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo" Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent. Dapagliflozin placebo: Dapagliflozin placebo looking similar to active drug Dapagliflozin in external appearance but not containing active ingredient dapagliflozin	Active Drugs n=17 participants at risk 12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug" Dapagliflozin: Dapagliflozin or Farxiga is a SGLT-2 inhibitor Insulin Liraglutide: Victoza(Liraglutide) is a GLP-1 agent.
Endocrine disorders DKA	0.00% 0/9 • 12 WEEKS	11.8% 2/17 • Number of events 2 • 12 WEEKS

Other adverse events

Adverse event data not reported

Additional Information

Paresh Dandona

State University of NY at Buffalo

Phone: 7165351852

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place