Trial · Interventional

CompletedPhase 3Results postedRegistry data

The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes

NCTNCT00856986Other idNN2211-1842Other id2007-005317-19

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 987 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Open label (no masking)
Countries: 10 countries
United States, Belgium, Canada, France, Germany, Italy, Netherlands, Puerto Rico, Spain, United Kingdom
Start: Mar 2009
Primary completion: Apr 2010
Completion: Nov 2010
First posted: 6 Mar 2009 (estimated)
Last update posted: 8 Mar 2017
Conditions: Diabetes · Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

200920102011

Ph 3
The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes
NCT00856986
Mar 2009 to Nov 2010

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This trial is conducted in Europe and North America. The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will continue their own pre-trial metformin treatment during the trial.

Interventions

liraglutideDrug
insulin detemirDrug
metforminDrug

Arms5

Experimental
Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
Experimental
Insulin detemir + Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
Experimental
Non-Randomised Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%
Other
Early Withdrawals Lira 1.8
Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial
Other
Intensified group
Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.

Primary outcomes1

Outcomes the sponsor listed as primary.

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26.
Time frame · Week 0 (Randomisation), week 26

Secondary outcomes(20)

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group)
Time frame · Week 0, Week 52
Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF)
Time frame · Week 0, Week 52
Mean Change From Randomisation in Fasting Plasma Glucose at Week 26
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Fasting Plasma Glucose at Week 52
Time frame · Week 0, Week 52
Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26
Time frame · Week 0 (Randomisation), Week 26
Registry description
Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline/randomisation (week 0) to 26 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52
Time frame · Week 0, Week 52
Registry description
Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline (week 0) to 52 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
Mean Change From Randomisation in Fasting Insulin at Week 26
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Fasting Insulin at Week 52
Time frame · Week 0 (Randomisation), Week 52
Mean Change From Randomisation in Fasting Pro-insulin at Week 26.
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Fasting Pro-insulin at Week 52
Time frame · Week 0, Week 52
Mean Change From Randomisation in Fasting C-peptide at Week 26.
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Fasting C-peptide at Week 52.
Time frame · Week 0, Week 52
Mean Changes From Randomisation in Cholesterol Lipids at Week 26.
Time frame · Week 0 (Randomisation), Week 26
Registry description
Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
Mean Changes From Randomisation in Cholesterol Lipids at Week 52.
Time frame · Week 0, Week 52
Registry description
Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
Mean Change From Randomisation in Lipids: Triglycerides at Week 26
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Lipids: Triglycerides at Week 52
Time frame · Week 0, Week 52
Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 26
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 52
Time frame · Week 0, Week 52
Mean Change From Randomisation in Body Weight at Week 26
Time frame · Week 0 (Randomisation), Week 26
Mean Change From Randomisation in Body Weight at Week 52
Time frame · Week 0, Week 52

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Week 0 (Randomisation), week 26

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26.

Group	Value (Percentage point of total HbA1c)	Spread
Lira 1.8	0.02	0.07
Insulin Detemir + Lira 1.8	-0.51	0.07
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary and other outcome results(7)

Secondary outcomeLeast squares mean· Week 0, Week 52

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group)

Group	Value (Percentage point of total HbA1c)	Spread
Lira 1.8	-0.1	0.09
Insulin Detemir + Lira 1.8	-0.51	0.09
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary outcomeLeast squares mean· Week 0, Week 52

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF)

Group	Value (Percentage point of total HbA1c)	Spread
Lira 1.8	0.01	0.09
Insulin Detemir + Lira 1.8	-0.5	0.09
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary outcomeLeast squares mean· Week 0 (Randomisation), Week 26

Mean Change From Randomisation in Fasting Plasma Glucose at Week 26

Group	Value (mmol/L)	Spread
Lira 1.8	-0.39	0.19
Insulin Detemir + Lira 1.8	-2.12	0.19
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary outcomeLeast squares mean· Week 0, Week 52

Mean Change From Randomisation in Fasting Plasma Glucose at Week 52

Group	Value (mmol/L)	Spread
Lira 1.8	-0.14	0.21
Insulin Detemir + Lira 1.8	-1.91	0.21
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary outcomeLeast squares mean· Week 0 (Randomisation), Week 26

Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26

Group	Value (mmol/L)	Spread
Lira 1.8	-0.97	0.26
Insulin Detemir + Lira 1.8	-2.09	0.26
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary outcomeLeast squares mean· Week 0, Week 52

Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52

Group	Value (mmol/L)	Spread
Lira 1.8	-0.68	0.25
Insulin Detemir + Lira 1.8	-2.43	0.25
Non-Randomised Lira 1.8	not posted	–
Early Withdrawals Lira 1.8	not posted	–
Intensified Group	not posted	–

Secondary outcome· Week 0 (Randomisation), Week 26

Mean Change From Randomisation in Fasting Insulin at Week 26

Group	Value
Lira 1.8	not posted
Insulin Detemir + Lira 1.8	not posted
Non-Randomised Lira 1.8	not posted
Early Withdrawals Lira 1.8	not posted
Intensified Group	not posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Lira 1.8Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	–	11 / 159	100 / 159
Insulin Detemir + Lira 1.8Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	–	17 / 163	102 / 163
Non-Randomised Lira 1.8Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	–	62 / 499	310 / 499
Early Withdrawals Lira 1.8Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	–	6 / 166	122 / 166
Intensified GroupIntensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.	–	1 / 24	11 / 24

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2013

7 results

One-year sustained glycemic control and weight reduction in type 2 diabetes after addition of liraglutide to metformin followed by insulin detemir according to HbA1c target.

Rosenstock et al. 2013Journal of diabetes and its complicationscited by 37

PMID 23746555DOI 10.1016/j.jdiacomp.2013.04.008PUB-23746555

Full text at the publisher7 results

Publisher page See results (7)

Indexing hint: Randomized controlled trial · 2012

11 results

Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets.

DeVries et al. 2012Diabetes carecited by 116

PMID 22584132PMC3379583DOI 10.2337/dc11-1928PUB-22584132

Free to read · publisher termsCC BY-NC-ND11 results

Read at source See results (11)

More studies

1 study on this page

Indexing hint: Meta-analysis (pooled) · 2015

Corrected

Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials.

Jensen et al. 2015Diabetes carecited by 45

PMID 25504028DOI 10.2337/dc13-1210PUB-25504028

Rights unknown

Source link Read the notice

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 84 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * Subjects diagnosed with type 2 diabetes, insulin naïve and treated with metformin as monotherapy for at least 3 months prior to screening, at a stable dose of at least 1500 mg/day or metformin (at least 1500 mg/day) and a sulfonylurea (less than or equal to half of the maximum approved dose), both at a stable dose for at least 3 months prior to screening. Previous short-term insulin treatment in connection with intercurrent illness is allowed at the discretion of the Investigator * HbA1c 7.0-10.0% (both inclusive) for subjects on metformin monotherapy * HbA1c 7.0-8.5% (both inclusive) for subjects on metformin in combination with a sulphonylurea Exclusion Criteria: * Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness at the discretion of the Investigator) * Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 3 months prior to screening * Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator * Impaired kidney function * Impaired liver function * Uncontrolled treated/untreated hypertension * Cancer or any clinically significant disease or disorder as judged by the Investigator * Previous participation in the run-in phase of this trial. Re-screening is allowed once * History of chronic pancreatitis or idiopathic pancreatitis

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