Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Liraglutide is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. FDA label
Also known as liraglutide [3H], Saxenda, Victoza, NNC 90-1170, IDegLira, insulin degludec
Liraglutide · 83 trials · 14 indications
The primary endpoint of the study is to detect a difference from baseline in mean weekly blood glucose concentrations before and after 12 weeks of treatment in each of the Liraglutide groups.
Percent
Drug-free diabetes remission is defined as HbA1C \< 6.5 % off glucose-lowering agents for at least 12 weeks.
HbA1c will be compared between study groups. HbA1c measures the average percentage of blood sugar over the past 2 to 3 months and HbA1c can reduce with management of diabetes through diet, exercise, and medication. HbA1c levels below 5.7% are considered normal. Persons with values between 5.7% and 6.4% are considered at high risk of developing diabetes while those with values of 6.5% and above are diagnosed with diabetes. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable.
Subjects calculated weight in kilograms
Change from baseline (week 0) to week 26 in glycosylated haemoglobin was evaluated for 2 different observation period 'in-trial' observation period and 'on-treatment without rescue medication" observation period. The 'in-trial' observation period represents the time-period where subjects were considered to be in the trial, regardless of whether or not the subjects had initiated rescue medication or prematurely discontinued trial product. The 'on-treatment' observation period is the part of the in-trial observation period during which subjects were treated with the trial product, that is the time from the first dose to the last dose of trial product. The 'on-treatment without rescue medication' observation period is a part of 'on-treatment' observation period during which subjects were considered treated with trial product and had not initiated any rescue medications.
Observed mean change in body weight from baseline (week 0) to week 56 was evaluated for two different observation periods. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). The test of superiority of liraglutide to placebo for the treatment policy estimand was tested in a hierarchical manner for the two primary and the consequent 7 confirmatory secondary endpoints presented.
The estimated mean percentage of subjects losing at least 5% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
The estimated percentage of participants losing at least 5% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events \[AEs\]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Changes from baseline on measurements of respiratory function defined by forced expiratory volume in 1 second (FEV1). Mean difference between 7 weeks after treatment visit and baseline visit is registered.
Change from baseline (week 0) in BMI SDS was evaluated at week 56. BMI SDS was calculated using the following formula: Z=\[(value /M)\^L - 1\] / S\*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (WHO) Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation. Results are based on both participants who completed the week 0-56 trial period and participants who prematurely discontinued the trial product but attended the follow-up visit at 56.
Change in BMI SDS from baseline to week 16 is presented. BMI SDS also called Z-scores, was calculated using the following formula: Z=\[(y / M)\^L - 1\] / S\*L; where L, M and S are median (M), Box-cox power (L) and variation coefficient (S) of children/adolescents', y= individual BMI. BMI provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. Possible values range from -3 to +3, a negative score being beneficial.
Change in BMI SDS from baseline to week 52 is presented. BMI SDS also called Z-scores, was calculated using the following formula: Z=\[(y / M)\^L - 1\] / S\*L; where L, M and S are median (M), Box-cox power (L) and variation coefficient (S) of children/adolescents', y= individual BMI. BMI provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. Possible values range from -3 to +3, a negative score being beneficial.
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated after 26 weeks of treatment. The change from baseline in the response after 26 weeks of treatment is analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline response as a covariate.
Change from baseline in glycosylated haemoglobin (HbA1c), after 26 weeks of treatment. Full analysis set (FAS = 831) included all randomised subjects who had received at least one dose and had any post-randomisation data.
Change from baseline in HbA1c at week 52. Missing values were handled by using a mixed model for repeated measurements (MMRM).
Change from baseline in body weight at week 52. Missing values were handled by using a MMRM.
Change from baseline in total daily insulin dose at week 52. Change from baseline was represented in terms of ratio to baseline for insulin dose i.e. Total daily insulin dose at week 52/total daily insulin dose at baseline. Missing values were handled by using a MMRM.
Change in HbA1c from baseline to week 26. All available data were used for the primary analysis, including data collected after treatment discontinuation and initiation of rescue medication.
The estimated mean change from baseline in HbA1c after 26 weeks of treatment.
Calculated as the estimated mean change from baseline in HbA1c (%) after 26 Weeks of treatment based on the statistical model.
Observed mean change from baseline in AHI (events/hour) after 32 weeks of treatment. AHI (apnoea and hypopnoea events per hour of sleep) is a measure used for the diagnosis and severity classification of obstructive sleep apnoea. AHI severity category: none ≤4.9; mild 5.0-14.9; moderate 15.0-29.9; severe ≥30.0 events/hour.
Estimated mean change from baseline in HbA1c after 16 Weeks of treatment.
Adverse events were defined as events occurring after administration of trial product and no later than 7 days after last day of treatment. Severe AEs: considerable interference with subject's daily activities. Moderate AEs: Marked symptoms, moderate interference with the subject's daily activities. Mild AEs: No or transient symptoms, no interference with the subject's daily activities. Serious AEs: AEs that resulted in any of the following: death, a life-threatening experience, hospitalization/prolongation of existing hospitalization, persistent/significant disability, and congenital anomaly.
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
The observed mean change from baseline in fasting body weight (%) after 56-weeks of treatment (main treatment period).
Percentage of subjects losing at least 5% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Percentage of subjects losing \>10% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Proportion of subjects with onset of Type 2 diabetes mellitus (T2DM) at week 160 (main + extension treatment period) among subjects with pre-diabetes at baseline - evaluated as time to onset of T2DM. Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time from randomisation to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (a composite cardiovascular outcome). The percentage of subjects experiencing a first event of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (a composite cardiovascular outcome) is presented.
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Subjects who had a weight regain less than or equal to 0.5% of weight from Week 0 were regarded as maintenance of run-in fasting weight loss. Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26.
Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 52.
Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 78.
Mean Change in Glycosylated Haemoglobin A1c (HbA1c) from Week 52 to Week 78
Assessed endothelial function by measuring the change in ACh-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.
Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment).
Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)
The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi), gastric emptying of solids was assessed with scintigraphy imaging.
Calculated as mean body weight at week 20 - baseline
Measured as count of participants.
Measured as count of participants.
Measured as count of participants.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Daily Injection |
| Liraglutide 1.8mg | ACTIVE_COMPARATOR | Daily Injection |
| Liraglutide 1.2mg | ACTIVE_COMPARATOR | Daily injections |
| Liraglutide 0.6 mg | ACTIVE_COMPARATOR | Daily injection |
| Liraglutide 3.0 mg | EXPERIMENTAL | The treatment duration is 56 weeks and the follow-up period is 26 weeks. |
| Intervention | EXPERIMENTAL | Drug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise |
| Standard Care | NO_INTERVENTION | Standard glycemic care as informed by the current clinical practice guidelines |
| IDegLira | EXPERIMENTAL | Participants in this group will receive IDegLira (with metformin, unless contraindicated) for 26 weeks. |
| Basal-Bolus Insulin | ACTIVE_COMPARATOR | Participants in this group will receive basal-bolus insulin (with metformin, unless contraindicated) for 26 weeks. The basal-bolus insulin regimen includes Insulin Degludec (U-100) and Insulin Aspart. |
| Sleeve Gastrectomy Placebo | PLACEBO_COMPARATOR | Subjects undergoing Sleeve Gastrectomy (SG) will be randomized 1:1 at the time of 3 month visit after bariatric surgery. |
| Sleeve Gastrectomy Saxenda | ACTIVE_COMPARATOR | Subjects undergoing Sleeve Gastrectomy (SG) will be randomized 1:1 at the time of 3 month visit after bariatric surgery. |
| RYGB | SHAM_COMPARATOR | Twenty five subjects will be recruited from the Nutrition Clinic at Mayo Clinic Rochester prior to undergoing RYGB surgery. |
| liraglutide + SGLT2i ± metformin | EXPERIMENTAL | - |
| liraglutide placebo + SGLT2i ± metformin | PLACEBO_COMPARATOR | - |
| Liraglutide | EXPERIMENTAL | - |
| Liraglutide 1.8 mg | EXPERIMENTAL | The total trial duration for the 1.8 mg/day treatment arm will be approximately 67 weeks, consisting of 2 weeks screening period, a 12 weeks run-in period, a 26-week main treatment period, a safety extension period of 26 weeks and a follow-up visit. |
| Liraglutide 0.9 mg | ACTIVE_COMPARATOR | The total trial duration for the 0.9 mg/day treatment arm will be approximately 41 weeks, consisting of 2 weeks screening period, a 12 weeks run-in period, a 26-week treatment period, and a follow-up visit. |
| Liraglutide 1.8 mg + insulin | EXPERIMENTAL | - |
| Liraglutide 1.2 mg + insulin | EXPERIMENTAL | - |
| Liraglutide 0.6 mg + insulin | EXPERIMENTAL | - |
| Liraglutide placebo 0.3 ml + insulin | PLACEBO_COMPARATOR | - |
| Liraglutide placebo 0.2 ml + insulin | PLACEBO_COMPARATOR | - |
| Liraglutide placebo 0.1 ml + insulin | PLACEBO_COMPARATOR | - |
| Liraglutide placebo 0.6 mg + insulin | PLACEBO_COMPARATOR | - |
| Liraglutide placebo 1.2 mg + insulin | PLACEBO_COMPARATOR | - |
| Liraglutide placebo 1.8 mg + insulin | PLACEBO_COMPARATOR | - |
| Lira + Met | EXPERIMENTAL | - |
| Placebo + Met | PLACEBO_COMPARATOR | - |
| Lira 1.8 mg | EXPERIMENTAL | - |
| Lira+Insulin | EXPERIMENTAL | - |
| Placebo+Insulin | PLACEBO_COMPARATOR | - |
| Liraglutide + an OAD therapy | EXPERIMENTAL | - |
| Two OADs combination therapy | ACTIVE_COMPARATOR | - |
| Lira 3.0 mg | EXPERIMENTAL | - |
| Liraglutide 3.0mg (week0-56)/Liraglutide 3.0mg (week56-68) | EXPERIMENTAL | - |
| Liraglutide 3.0mg (week0-56)/Liraglutide Placebo (week56-68) | EXPERIMENTAL | - |
| Liraglutide Placebo, no Pre-diabetes | PLACEBO_COMPARATOR | - |
| Liraglutide 3.0mg, Pre-diabetes | EXPERIMENTAL | - |
| Liraglutide Placebo, Pre-diabetes | PLACEBO_COMPARATOR | - |
| Lira 1.8 | EXPERIMENTAL | 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% |
| Insulin detemir + Lira 1.8 | EXPERIMENTAL | 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% |
| Non-Randomised Lira 1.8 | EXPERIMENTAL | 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% |
| Early Withdrawals Lira 1.8 | OTHER | 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 |
| Intensified group | OTHER | 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. |
| Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg | EXPERIMENTAL | Once-daily subcutaneous dose of liraglutide 1.2 mg with at least 1500 mg metformin/day (tablets) for 26 weeks. First week for up-titration of liraglutide from 0.6 mg to 1.2 mg. Subjects continued to receive liraglutide 1.2 mg once daily in extension period 1 (weeks 26-52) and extension period 2 (weeks 52-78). |
| Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg | EXPERIMENTAL | Once-daily subcutaneous dose of liraglutide 1.8 mg with at least 1500 mg metformin/day (tablets) for 26 weeks. First 2 weeks for up-titration of liraglutide from 0.6 mg to 1.8 mg. Subjects continued to receive liraglutide 1.8 mg once daily in extension period 1 (weeks 26-52) and extension period 2 (weeks 52-78). |
| Sita -> Sita | ACTIVE_COMPARATOR | Once-daily dose of sitagliptin 100 mg (tablets) with at least 1500 mg metformin/day (tablets) for 26 weeks. Subjects continued to receive 100 mg sitagliptin once daily in extension period 1 (weeks 26-52). |
| Sita -> Sita -> Lira 1.2 mg | EXPERIMENTAL | Once-daily dose of sitagliptin 100 mg (tablets) with at least 1500 mg metformin/day (tablets) for 26 weeks. Subjects continued to receive 100 mg sitagliptin once daily in extension period 1 (weeks 26-52). In extension period 2 (weeks 52-78), subjects were randomised to liraglutide 1.2 mg + metformin. |
| Sita -> Sita -> Lira 1.8 mg | EXPERIMENTAL | Once-daily dose of sitagliptin 100 mg (tablets) with at least 1500 mg metformin/day (tablets) for 26 weeks. Subjects continued to receive 100 mg sitagliptin once daily in extension period 1 (weeks 26-52). In extension period 2 (weeks 52-78), subjects were randomised to liraglutide 1.8 mg + metformin. |
| Glimepiride | ACTIVE_COMPARATOR | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Lira 0.6 + Met | EXPERIMENTAL | Liraglutide 0.6 mg + metformin + glimepiride placebo |
| Lira 1.2 + Met | EXPERIMENTAL | Liraglutide 1.2 mg + metformin + glimepiride placebo |
| Lira 1.8 + Met | EXPERIMENTAL | Liraglutide + metformin + glimepiride placebo |
| Glim + Met | EXPERIMENTAL | Glimepiride 4.0 mg + metformin + liraglutide placebo |
| Exenatide | ACTIVE_COMPARATOR | Exenatide 10 mcg twice daily + subject's own OAD treatment |
| Glibenclamide | ACTIVE_COMPARATOR | Glibenclamide 1.25-2.5 mg + liraglutide placebo |
| 0.6 mg + SU | EXPERIMENTAL | Liraglutide 0.6 mg + sulphonylurea |
| 0.9 mg + SU | EXPERIMENTAL | Liraglutide 0.9 mg + sulphonylurea |
| SU Mono - 1 | PLACEBO_COMPARATOR | Liraglutide placebo 0.6 mg + sulphonylurea |
| SU Mono - 2 | PLACEBO_COMPARATOR | Liraglutide placebo 0.9 mg + sulphonylurea |
| Met Mono | ACTIVE_COMPARATOR | Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo |
| Met + Glim | ACTIVE_COMPARATOR | Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo |
| Treatment Period: Placebo QD | PLACEBO_COMPARATOR | Participants will receive daily SC placebo injections during the 12-week, double-blind treatment period. |
| Treatment Period: NNC0090-2746 QD | EXPERIMENTAL | Participants will receive daily 1.8-mg SC injections of NNC0090-2746 during the 12-week, double-blind treatment period. |
| Treatment Period: Liraglutide QD | ACTIVE_COMPARATOR | Participants will receive open-label liraglutide via SC injection during the 12-week treatment period. The dose scheme will be as follows: 0.6 milligrams (mg) each day during Week 1, followed by 1.2 mg each day during Week 2, and 1.8 mg each day from Weeks 3 to 12. |
| Lira placebo/Lira 2.4 mg/Lira 3.0 mg | PLACEBO_COMPARATOR | Liraglutide placebo once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104) |
| Lira 1.2 mg/Lira 3.0 mg | EXPERIMENTAL | Liraglutide 1.2 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104) |
| Lira 1.8 mg/Lira 3.0 mg | EXPERIMENTAL | Liraglutide 1.8 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104) |
| Lira 2.4 mg/Lira 3.0 mg | EXPERIMENTAL | Liraglutide 2.4 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104) |
| Orlistat | ACTIVE_COMPARATOR | Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal, weeks 0-20 (open-label) continued to receive Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal in open-label extension period (weeks 20-104) |
| NNC 90-1170 + Met | EXPERIMENTAL | - |
| NNC 90-1170 + Met placebo | EXPERIMENTAL | - |
| Met + NNC 90-1170 placebo | PLACEBO_COMPARATOR | - |
| NNC 90-1170 | EXPERIMENTAL | - |
| Treatment period 1 | EXPERIMENTAL | - |
| Treatment period 2 | PLACEBO_COMPARATOR | - |
| 0.045 mg | EXPERIMENTAL | - |
| 0.225 mg | EXPERIMENTAL | - |
| 0.45 mg | EXPERIMENTAL | - |
| 0.60 mg | EXPERIMENTAL | - |
| 0.75 mg | EXPERIMENTAL | - |
| Met | ACTIVE_COMPARATOR | - |
| Glim | ACTIVE_COMPARATOR | - |
| Oral semaglutide | EXPERIMENTAL | Participants will receive semaglutide orally. |
| Semaglutide | EXPERIMENTAL | Participants will receive semaglutide subcutaneously. |
| Liraglutide 0.6 mg s.c. with FlexPen® | EXPERIMENTAL | - |
| Liraglutide 0.6 mg s.c. with the PDS290 pen-injector | EXPERIMENTAL | - |
| Low | EXPERIMENTAL | - |
| Medium | EXPERIMENTAL | - |
| High | EXPERIMENTAL | - |
| I.a | EXPERIMENTAL | - |
| I.b | PLACEBO_COMPARATOR | - |
| II.a | EXPERIMENTAL | - |
| II.b | PLACEBO_COMPARATOR | - |
| A | EXPERIMENTAL | - |
| B | PLACEBO_COMPARATOR | - |
| C | EXPERIMENTAL | - |
| D | EXPERIMENTAL | - |
| E | EXPERIMENTAL | - |
| F | EXPERIMENTAL | - |
| A1 | EXPERIMENTAL | - |
| A2 | PLACEBO_COMPARATOR | - |
| B1 | EXPERIMENTAL | - |
| B2 | PLACEBO_COMPARATOR | - |
| C1 | EXPERIMENTAL | - |
| C2 | PLACEBO_COMPARATOR | - |
| Abdomen | EXPERIMENTAL | - |
| Thigh | EXPERIMENTAL | - |
| Upper arm | EXPERIMENTAL | - |
| Formulation 4 | EXPERIMENTAL | - |
| Final formulation 4 | EXPERIMENTAL | - |
| Double-blind / liraglutide | EXPERIMENTAL | - |
| Double-blind / placebo | PLACEBO_COMPARATOR | - |
| Open-label / moxifloxacin | ACTIVE_COMPARATOR | - |
| Open-label / placebo | PLACEBO_COMPARATOR | - |
| Trial period A | EXPERIMENTAL | - |
| Trial period B | EXPERIMENTAL | - |
| Formulation 3 | EXPERIMENTAL | - |
| Mild | EXPERIMENTAL | - |
| Moderate | EXPERIMENTAL | - |
| Severe | EXPERIMENTAL | - |
| Normal | EXPERIMENTAL | - |
| 15 mcg/kg | EXPERIMENTAL | - |
| 20 mcg/kg | EXPERIMENTAL | - |
| 25 mcg/kg | EXPERIMENTAL | - |
| Lira --> placebo | EXPERIMENTAL | - |
| Placebo --> glim | PLACEBO_COMPARATOR | - |
| Glim --> lira | ACTIVE_COMPARATOR | - |
| Normal renal function | EXPERIMENTAL | - |
| Mild renal impairment | EXPERIMENTAL | - |
| Moderate renal impairment | EXPERIMENTAL | - |
| Severe renal impairment | EXPERIMENTAL | - |
| End-stage renal disease | EXPERIMENTAL | - |
| pH 7.7 | EXPERIMENTAL | - |
| pH 7.9 | EXPERIMENTAL | - |
| pH 8.15 | EXPERIMENTAL | - |
| Phase 2 formulation | EXPERIMENTAL | - |
| Phase 3 formulation | EXPERIMENTAL | - |
| Elderly | EXPERIMENTAL | - |
| Young | EXPERIMENTAL | - |
| Fixed dose: 5 mcg/kg | EXPERIMENTAL | - |
| Escalated dose: 10 mcg/kg | EXPERIMENTAL | - |
| 5 mcg/kg | EXPERIMENTAL | - |
| 10 mcg/kg | EXPERIMENTAL | - |
| NNC 90-1170, initial dose | EXPERIMENTAL | - |
| Insulin | ACTIVE_COMPARATOR | - |
| NNC 90-1170, final dose | EXPERIMENTAL | - |
| Healthy | NO_INTERVENTION | - |
| NNC 90-1170 (liraglutide) | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Liraglutide | DRUG | Patients randomized to 1.2 mg of liraglutide : They will start liraglutide 0.6 mg sc once daily for one week and will increase the dose to 1.2 mg sc once daily thereafter. Patients randomized to 1.8 mg of liraglutide: They will start liraglutide 0.6 mg sc once daily for one week; will increase to 1.2 mg sc once daily for second week and will stay on 1.8 mg of liraglutide from third week onwards. |
| Placebo | DRUG | Patients randomized to 1.2 mg of placebo: They will start placebo 0.6 mg sc once daily for one week and then increase to 1.2 mg once daily thereafter. Patients randomized to 1.8 mg of placebo: They will start placebo 0.6 mg sc once daily for one week; increase to 1.2 mg sc once daily for second week and then to 1.8 mg sc once daily from third week onwards. |
| IDegLira | DRUG | Dose is titrated to achieve fasting normoglycemia |
| insulin degludec | DRUG | In those who need additional insulin or who cannot tolerate IDegLira, insulin degludec will be used. Dose is titrated to achieve fasting normoglycemia. |
| Metformin | DRUG | Dose is titrated to 2000 mg per day or maximal tolerated dose |
| Lifestyle Therapy | BEHAVIORAL | Lifestyle intervention includes individualized dietary and exercise advice targeting at least 5% weight loss with frequent visits and coaching for goal reinforcement, behavior modification and problem-solving |
| Insulin Degludec (U-100) | DRUG | Participants in the basal-bolus insulin study arm will discontinue all other diabetes medications, except for metformin which will be continued at the prescribed dose (unless contraindicated). Insulin Degludec (U-100) will be given once daily at the same time for 26 weeks. The dose will be titrated up to the fasting blood glucose target of 70 to 100 mg/dL, with no maximum dose. |
| Insulin Aspart | DRUG | Participants in the basal-bolus insulin study arm will discontinue all other diabetes medications, except for metformin which will be continued at the prescribed dose (unless contraindicated). Insulin aspart will be taken before meals with a titration schedule and dose adjustment protocol to target pre-meal blood glucose level of 70 to 100 mg/dL. |
| Saxenda | DRUG | Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adult patients. Subjects will be recruited and screened prior to undergoing bariatric surgery. Subjects undergoing SG will be randomized 1:1 at month 3 post surgery to Saxenda, 0.6mg SQ daily, with weekly titration of 0.6mg until maintenance dose of 3mg/daily reached. Subjects will remain on study drug for duration of study (33 months). After undergoing surgery, study visits will be timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36. |
| Placebos | DRUG | Subjects will be recruited and screened prior to undergoing bariatric surgery.Subjects undergoing SG will be randomized 1:1 at months 3 post surgery to Placebo, 0.6mg SQ daily, with weekly titration of 0.6mg until maintenance dose of 3mg/daily reached. Subjects will remain on study drug for duration of study (33 months). After undergoing surgery, study visits will be timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36. |
| RYGB | PROCEDURE | Subjects will be recruited and screened prior to undergoing bariatric surgery. After undergoing surgery, study visits will be timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36. |
| CMS Intensive Behavior Therapy | BEHAVIORAL | Intensive Behaviour Therapy for obesity |
| Liraglutide 3.0 mg | DRUG | Injected subcutaneously (s.c., under the skin) once daily |
| insulin | DRUG | All subjects will continue their pre-trial insulin therapy (basal, premixed or basal-bolus regimen) during the trial. Insulin dose is fixed for the first 16 weeks and for the subsequent 20 weeks, insulin dose is individually adjusted. |
| oral anti-diabetic drug | DRUG | An additional oral anti-diabetic drug (OAD) with a different mechanism of action than the pre-trial OAD. The type and dosage of the additional OAD should be chosen by the investigator within the Japanese labelled dose. |
| insulin detemir | DRUG | Insulin detemir subcutaneous (under the skin) injection once daily. Dose will be titrated (individually adjusted) based on fasting self-measured plasma glucose levels according to a pre-specified algorithm |
| sitagliptin | DRUG | Tablets, 100 mg daily |
| glimepiride | DRUG | Tablets, 1 - 4 mg daily |
| exenatide | DRUG | 10 mcg twice daily for s.c. (under the skin) injection. |
| glibenclamide | DRUG | 1.25-2.5 mg tablet. Given orally once or twice daily. |
| sulfonylurea | DRUG | SU agent |
| rosiglitazone | DRUG | - |
| insulin glargine | DRUG | - |
| Mixed Meal Tolerance Test with paracetamol | DRUG | At the beginning and end of each period (Visit 2a, 8, 9a, 15) a Mixed Meal Tolerance Test enriched paracetamol will be performed. |
| NNC0090-2746 | DRUG | NNC0090-2746 solution will be self-administered in daily doses of 1.8 mg via SC injection. |
| Liraglutide-placebo | OTHER | 1.8 mg once-daily, subcutaneous injection |
| orlistat | DRUG | 120 mg capsule. Administered thrice daily |
| Oral Semaglutide | DRUG | Participants will receive semaglutide orally. |
| Semaglutide | DRUG | Participants will receive semaglutide subcutaneously. |
| liraglutide [3H] | DRUG | A single dose of 0.75 mg will be given as a subcutaneous injection |
| levonorgestrel / ethinylestradiol | DRUG | One single oral tablet after the liraglutide or placebo dose administration at the end of each treatment period |
| paracetamol | DRUG | One single dose of 1 g. Tablet |
| moxifloxacin | DRUG | Following the double-blinded period and a wash-out period of 7 days, subjects are re-randomised to an open-label, parallel period where a single dose of 400 mg moxifloxacin (tablets) is administered as positive control |
| electrocardiogram (ECG) | PROCEDURE | 24 hours serial ECG is collected before initial dose of 0.6 mg liraglutide, on the last dosing day of 1.2 mg liraglutide and on the last dosing day of 1.8 mg liraglutide |
| atorvastatin | DRUG | One single dose of 40 mg. Tablet |
| lisinopril | DRUG | One single dose of 20 mg. Tablet |
| griseofulvin | DRUG | One single dose of 500 mg. Tablet |
| digoxin | DRUG | One single dose of 1 mg. Tablet |
| insulin human | DRUG | Single dose 0.4 IU/kg by inhalation. Subjects receive treatment in random order |
Inclusion Criteria: 1. Patients with type 1 diabetes mellitus: Fasting c-peptide \< 0.1nmol/l on insulin therapy for more than 12 months with or without history of diabetic ketoacidosis. 2. Using a continuous glucose monitoring device (CGM) and regularly measuring their blood sugars four times dail...
Liraglutide is used to treat diabetes, obesity, and metabolism and nutrition disorders, and it is being studied in nonalcoholic steatohepatitis, type 1 diabetes, and type 1 diabetes mellitus. It is a small molecule GLP-1 receptor agonist developed by Novo Nordisk A/S.
Liraglutide targets GLP1R, the glucagon-like peptide-1 receptor, and acts as an agonist at that receptor. This receptor target underlies its use across metabolic conditions including diabetes and obesity.
Liraglutide is developed by Novo Nordisk A/S, which trades under the ticker NVO. Novo Nordisk is the sponsor behind the clinical development program for the drug across its metabolic indications.
Liraglutide is in Phase 3 development. It is an investigational small molecule GLP-1 receptor agonist, and its clinical program spans diabetes, obesity, and related metabolic conditions.
Liraglutide has been studied in 58 trials with about 22,988 participants, including NCT04775082, a Phase 3 obesity study in children, and NCT03523273, a Phase 2 obesity study. NCT07225816 is a recruiting Phase 1 trial in obesity.
Saxenda is another name for liraglutide, along with liraglutide [3H] and Liraglutide 3.0 mg. People searching for Saxenda are looking at the same liraglutide asset developed by Novo Nordisk A/S.