Diabetes Mellitus, Type 1Phase 4NCT01612468
Liraglutide in Type 1 Diabetes
A Phase 4 study testing Liraglutide in people with Diabetes Mellitus, Type 1 and Overweight, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 1, Overweight
- What is being tested?
- Liraglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2012to Feb 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes according to WHO criteria ≥ 1 year
- Age ≥ 18 years
- BMI > 25 kg/m2
- HbA1c > 8.0 % at visit 0
Who cannot join
- Insulin pump treatment
- Hypoglycaemia unawareness (unability to register low blood glucose)
- Diabetic gastroparesis
- Compromised kidney function (eGFR < 60 ml/min/1,73m2), dialysis or kidney transplantation at visit 0
- Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
- Acute or chronic pancreatitis
Show all 16Show fewer
- Inflammatory bowel disease
- Cancer unless in complete remission for > 5 years
- History of thyroid adenoma or carcinoma
- Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation
- Alcohol/drug abuse
- Fertile women not using contraceptives
- Pregnant or nursing women
- Known or suspected hypersensitivity to trial product or related products
- Receipt of an investigational drug within 30 days prior to visit 0
- Simultaneous participation in any other clinical intervention trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Liraglutide in Type 1 Diabetes. A Randomised, Double-blind, Placebo Controlled Study of the Effect of Liraglutide as an Additional Treatment to Insulin on HbA1c, Body Weight and Hypoglycaemia in Poorly Regulated Type 1 Diabetes Patients
A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients.
Background: Treatment with glucagon-like peptid 1 (GLP-1) agonists liraglutide and exanatide leads to weight loss and decrease in haemoglobin A1c in oral anti diabetic treated type 2 diabetes patients.
Read more
It is estimated that 40-50 % of type 1 diabetes patients in the US suffers from overweight or poor glycaemic control (HbA1c > 8 %).
Small studies, not placebo controlled, reports effects of adding liraglutide to a group of well regulated (HbA1c < 7.5 %) normal to overweight insulin treated type 1 diabetes patients for 24 weeks. A decrease in HbA1c, weight, insulin doses and glycaemic excursions measured by continuous glucose monitoring was seen.
Primary objective:To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an add-on therapy to insulin. Secondary objectives:To investigate the effect of liraglutide as an add-on therapy to insulin compared to placebo on change in:Weight, insulin dose,hypoglycaemic events, CGM, BMI, body composition, quality of life, treatment satisfaction,food preferences, meal test, CIMT, PWV and 24 hour blood pressure.
Read the detailed description
A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients.
Background Treatment with glucagon-like peptid 1 (GLP-1) agonists liraglutide and exenatide leads to weight loss and decrease in haemoglobin A1c (HbA1c) in oral anti diabetic treated type 2 diabetes patients. Smaller studies have shown similar effects in insulin treated type 2 diabetes patients, with no increased risk of hypoglycaemia.
It is estimated that 40-50 % of type 1 diabetes patients in the US suffers from overweight or poor glycaemic control (HbA1c > 8 %). At present treatment of type 1 diabetes solely consists of insulin injections.
A recent study reports effects of adding liraglutide to a group of well regulated (HbA1c < 7.5 %) normal to overweight insulin treated type 1 diabetes patients for 24 weeks. A decrease in HbA1c, weight, insulin doses and glycaemic excursions measured by continuous glucose monitoring was seen. The study was not placebo controlled.
The available literature suggests that GLP-1 agonists reduce insulin dose and weight in well regulated type 1 diabetes patients, who are normal- to overweight. To our knowledge, no study has addressed whether liraglutide will improve HbA1c and reduce bodyweight in overweight and poorly regulated type 1 diabetes patients.
At present the most efficient way to reduce HbA1c is to use insulin pump therapy, and most studies suggest that this will decreased HbA1c by approximately 0.5 %. Insulin pump therapy is however only an option in very compliant patients. In most clinics treating type 1 diabetes 40-50 % of patients will have HbA1c > 8 % and many of these patients will, due to insufficient compliance, not be candidates for an insulin pump.
At Steno Diabetes Center approximately 3000 well characterized type 1 diabetes patients is followed in the outpatient clinic, and 40-50 % of these have HbA1c > 8.0 %. If liraglutide given once daily results in a reduction of HbA1c of 0.5 % it will probably be a very cost-effective additional therapy for type 1 diabetes patients in insufficient metabolic control.
Several studies have shown that liraglutide lowers systolic blood pressure. Dysregulation increases the risk of microvascular complications in type 1 diabetes of which microalbuminuria results in a need for treatment with antihypertensive medication. Overweight increases the risk of hypertension and arteriosclerosis and thereby cardiovascular diseases. Carotis intima media thickness is a validated estimate for future cardiovascular disease and pulse wave velocity is a measure of arterial stiffness. We perform 24 hour blood pressure measurements to document possible effects of liraglutide on blood pressure and CIMT and PWV to investigate the effect of liraglutide on cardiovascular disease and arteriosclerosis.
- Conditions
- Diabetes Mellitus, Type 1, Overweight
- Being tested
- Liraglutide, Placebo
- Keywords
- Diabetes, Liraglutide, Hypoglycaemia, Hyperglycaemia, CIMT, PWV, Food preference, Blood pressure
- Medical subject headings
- Diabetes Mellitus, Type 1, Overweight, Diabetes Mellitus, Hypoglycemia, Hyperglycemia, Food Preferences
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called Victoza
1.8 mg/day subcutaneous
PlaceboDrug
1.8 mg/day subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | Not described Receives: Drug: Liraglutide |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1c
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an adjunctive therapy to insulin treatment.
Measured: 24 week
Secondary outcomes (5)
Body weight
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in weight, BMI and body composition
Measured: 24 weeks
Cardiovascular
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in carotis intima media thickness, pulse wave velocity, 24 hour blood pressure
Measured: 24 weeks
Standardised liquid meal test
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in postprandial glucagon levels, glycaemic excursion, gastric emptying, VAS score for appetite and food preference
Measured: 24 weeks
Glycaemic excursions
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in insulin dose, hypoglycaemic events and glycaemic excursions (time spent in hypo- and hyperglycaemia as measured by CGM)
Measured: 24 weeks
Quality of life
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in quality of life and treatment satisfaction
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study startJun 2012
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, University of Copenhagen
- Responsible party
- Principal investigator, Lise Tarnow, Steno Diabetes Center Copenhagen
- Investigators
- Henrik U Andersen, DMSc, Principal investigator, Steno Diabetes Center Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01612468
- Sponsor's protocol ID
- Lira1
- Status last verified
- Jan 2016
- First submitted
- 11 May 2012
- Last updated
- 27 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dejgaard TF, Frandsen CS, Hansen TS, Almdal T, Urhammer S, Pedersen-Bjergaard U, Jensen T, Jensen AK, Holst JJ, Tarnow L, Knop FK, Madsbad S, Andersen HU. Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2016 Mar;4(3):221-232. doi: 10.1016/S2213-8587(15)00436-2. Epub 2015 Dec 3.
PubMed 26656289Dejgaard TF, Knop FK, Tarnow L, Frandsen CS, Hansen TS, Almdal T, Holst JJ, Madsbad S, Andersen HU. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes--a protocol for a randomised, double-blind, placebo-controlled study: the Lira-1 study. BMJ Open. 2015 Apr 2;5(4):e007791. doi: 10.1136/bmjopen-2015-007791.
PubMed 25838513
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liraglutide in Type 1 Diabetes. A Randomised, Double-blind, Placebo Controlled Study of the Effect of Liraglutide as an Additional Treatment to Insulin on HbA1c, Body Weight and Hypoglycaemia in Poorly Regulated Type 1 Diabetes Patients
- ClinicalTrials.gov ID
- NCT01612468
- Acronym / sponsor ID
- Lira1
- Conditions
- Diabetes Mellitus, Type 1, Overweight
- Keywords
- Diabetes, Liraglutide, Hypoglycaemia, Hyperglycaemia, CIMT, PWV, Food preference, Blood pressure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, University of Copenhagen
- Study start
- Jun 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 5 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients.
Background: Treatment with glucagon-like peptid 1 (GLP-1) agonists liraglutide and exanatide leads to weight loss and decrease in haemoglobin A1c in oral anti diabetic treated type 2 diabetes patients.
It is estimated that 40-50 % of type 1 diabetes patients in the US suffers from overweight or poor glycaemic control (HbA1c > 8 %).
Small studies, not placebo controlled, reports effects of adding liraglutide to a group of well regulated (HbA1c < 7.5 %) normal to overweight insulin treated type 1 diabetes patients for 24 weeks. A decrease in HbA1c, weight, insulin doses and glycaemic excursions measured by continuous glucose monitoring was seen.
Primary objective:To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an add-on therapy to insulin. Secondary objectives:To investigate the effect of liraglutide as an add-on therapy to insulin compared to placebo on change in:Weight, insulin dose,hypoglycaemic events, CGM, BMI, body composition, quality of life, treatment satisfaction,food preferences, meal test, CIMT, PWV and 24 hour blood pressure.
Detailed description
A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients.
Background Treatment with glucagon-like peptid 1 (GLP-1) agonists liraglutide and exenatide leads to weight loss and decrease in haemoglobin A1c (HbA1c) in oral anti diabetic treated type 2 diabetes patients. Smaller studies have shown similar effects in insulin treated type 2 diabetes patients, with no increased risk of hypoglycaemia.
It is estimated that 40-50 % of type 1 diabetes patients in the US suffers from overweight or poor glycaemic control (HbA1c > 8 %). At present treatment of type 1 diabetes solely consists of insulin injections.
A recent study reports effects of adding liraglutide to a group of well regulated (HbA1c < 7.5 %) normal to overweight insulin treated type 1 diabetes patients for 24 weeks. A decrease in HbA1c, weight, insulin doses and glycaemic excursions measured by continuous glucose monitoring was seen. The study was not placebo controlled.
The available literature suggests that GLP-1 agonists reduce insulin dose and weight in well regulated type 1 diabetes patients, who are normal- to overweight. To our knowledge, no study has addressed whether liraglutide will improve HbA1c and reduce bodyweight in overweight and poorly regulated type 1 diabetes patients.
At present the most efficient way to reduce HbA1c is to use insulin pump therapy, and most studies suggest that this will decreased HbA1c by approximately 0.5 %. Insulin pump therapy is however only an option in very compliant patients. In most clinics treating type 1 diabetes 40-50 % of patients will have HbA1c > 8 % and many of these patients will, due to insufficient compliance, not be candidates for an insulin pump.
At Steno Diabetes Center approximately 3000 well characterized type 1 diabetes patients is followed in the outpatient clinic, and 40-50 % of these have HbA1c > 8.0 %. If liraglutide given once daily results in a reduction of HbA1c of 0.5 % it will probably be a very cost-effective additional therapy for type 1 diabetes patients in insufficient metabolic control.
Several studies have shown that liraglutide lowers systolic blood pressure. Dysregulation increases the risk of microvascular complications in type 1 diabetes of which microalbuminuria results in a need for treatment with antihypertensive medication. Overweight increases the risk of hypertension and arteriosclerosis and thereby cardiovascular diseases. Carotis intima media thickness is a validated estimate for future cardiovascular disease and pulse wave velocity is a measure of arterial stiffness. We perform 24 hour blood pressure measurements to document possible effects of liraglutide on blood pressure and CIMT and PWV to investigate the effect of liraglutide on cardiovascular disease and arteriosclerosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Drug: Liraglutide |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 1 diabetes according to WHO criteria ≥ 1 year
- Age ≥ 18 years
- BMI > 25 kg/m2
- HbA1c > 8.0 % at visit 0
Key exclusion criteria (16 listed)
- Insulin pump treatment
- Hypoglycaemia unawareness (unability to register low blood glucose)
- Diabetic gastroparesis
- Compromised kidney function (eGFR < 60 ml/min/1,73m2), dialysis or kidney transplantation at visit 0
- Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiraglutideAlso: Victoza1.8 mg/day subcutaneous | Drug | Liraglutide |
| Placebo1.8 mg/day subcutaneous | Drug | Placebo |
Primary outcome
Change in HbA1c
Time frame: 24 week
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an adjunctive therapy to insulin treatment.
5 secondary outcomes
Body weight
Time frame: 24 weeks
Cardiovascular
Time frame: 24 weeks
Standardised liquid meal test
Time frame: 24 weeks
Glycaemic excursions
Time frame: 24 weeks
Quality of life
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2016.
- Derived from this study: PubMed 26656289Dejgaard TF, Frandsen CS, Hansen TS, Almdal T, Urhammer S, Pedersen-Bjergaard U, Jensen T, Jensen AK, Holst JJ, Tarnow L, Knop FK, Madsbad S, Andersen HU. Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2016 Mar;4(3):221-232. doi: 10.1016/S2213-8587(15)00436-2. Epub 2015 Dec 3.
- Derived from this study: PubMed 25838513Dejgaard TF, Knop FK, Tarnow L, Frandsen CS, Hansen TS, Almdal T, Holst JJ, Madsbad S, Andersen HU. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes--a protocol for a randomised, double-blind, placebo-controlled study: the Lira-1 study. BMJ Open. 2015 Apr 2;5(4):e007791. doi: 10.1136/bmjopen-2015-007791.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik U Andersen, DMSc principal investigator
Steno Diabetes Center Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liraglutide in people with Diabetes Mellitus, Type 1 and Overweight, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HbA1c (time frame: 24 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01612468, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2016.