NCT02963922: SCALE™ Insulin

Effect and Safety of Liraglutide 3.0 mg in Subjects With Overweight or Obesity and Type 2 Diabetes Mellitus Treated With Basal Insulin

Completed Phase 3 Results posted Last updated 30 March 2020

What this trial tests

Phase 3 trial testing Liraglutide 3.0 mg in Metabolism and Nutrition Disorder in 396 participants. Completed in 25 September 2018.

Timeline

6 February 2017

Primary endpoint
10 September 2018

25 September 2018

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	396
Start date	6 February 2017
Primary completion	10 September 2018
Estimated completion	25 September 2018
Sites	54 locations across Italy, Israel, Germany, Mexico, Canada, United States, Turkey (Türkiye)

Drugs / interventions tested

• Liraglutide 3.0 mg — full drug profile →
• Placebo

Conditions studied

• Metabolism and Nutrition Disorder — all drugs for Metabolism and Nutrition Disorder →
• Obesity — all drugs for Obesity →

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

18 and older, any sex, with Metabolism and Nutrition Disorder or Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Body Weight (%) Primary · Week 0, week 56

Change in body weight from baseline (week 0) to 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 b

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-6.0	± 6.0
Placebo	-1.5	± 5.4

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-6.5	± 5.8
Placebo	-1.7	± 5.2

Participants Losing at Least 5% of Baseline Body Weight Primary · Week 56

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 po

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	51.80
Placebo	23.98

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	56.92
Placebo	21.83

Participants Losing More Than 10% of Baseline Body Weight at Week 56 Secondary · Week 56

The estimated percentage of participants losing more than 10% 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

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	22.77
Placebo	6.55

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	22.56
Placebo	5.58

Change in Waist Circumference Secondary · Week 0, week 56

Change in waist circumference from baseline (week 0) to 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 AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-5.40	± 6.06
Placebo	-2.60	± 5.72

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-5.71	± 6.05
Placebo	-2.78	± 5.63

Change in HbA1c Secondary · Week 0, week 56

Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to 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 AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-1.1	± 1.2
Placebo	-0.5	± 1.2

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-1.2	± 1.1
Placebo	-0.7	± 1.0

Change in FPG Secondary · Week 0, week 56

Change in fasting plasma glucose (FPG) from baseline (week 0) to 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 AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-0.91	± 3.13
Placebo	-0.68	± 3.04

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	-1.05	± 3.08
Placebo	-0.96	± 2.68

Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score Secondary · Week 0, week 56

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	2.5	± 7.9
Placebo	2.6	± 7.3

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	2.9	± 7.8
Placebo	2.5	± 7.1

Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT), Physical Function Domain (5-items) Score Secondary · Week 0, week 56

Change in IWQoL-Lite for CT physical function domain (5-items) score. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. The endpoint 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: incl

In-trial observation period

Group	Value	95% CI
Liraglutide 3.0 mg	7.3	± 22.5
Placebo	6.8	± 21.5

On-drug observation period

Group	Value	95% CI
Liraglutide 3.0 mg	8.2	± 20.9
Placebo	6.5	± 21.8

Change in Total Daily Insulin Dose (U) Secondary · Week 0, week 56

Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial 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.

Group	Value	95% CI
Liraglutide 3.0 mg	3	± 30
Placebo	18	± 38

Change in Total Daily Basal Insulin Dose (% of Pre-trial Dose in U) Secondary · Week 0, week 56

Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial 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.

Group	Value	95% CI
Liraglutide 3.0 mg	19	± 121
Placebo	64	± 139

Change in Total Daily Basal Insulin Dose (U/kg) Secondary · Week 0, week 56

Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial 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.

Group	Value	95% CI
Liraglutide 3.0 mg	0.05	± 0.33
Placebo	0.15	± 0.30

Change in Total Daily Insulin Dose (U/kg) Secondary · Week 0, week 56

Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial 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.

Group	Value	95% CI
Liraglutide 3.0 mg	0.05	± 0.33
Placebo	0.18	± 0.37

Adverse events — posted to ClinicalTrials.gov

Time frame: From the date of first dose of trial product (week 0) to end of treatment (week 56) + post treatment follow-up of 30 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Liraglutide 3.0 mg

Serious: 16/195 (8%)

Deaths: 0/195

Placebo

Serious: 19/197 (10%)

Deaths: 0/197

Serious adverse events (46 terms)

Reaction	System	Liraglutide 3.0 mg	Placebo
Atrial flutter	Cardiac disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Amylase increased	Investigations	—	—
Angina pectoris	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Cellulitis	Infections and infestations	—	—
Coronary artery disease	Cardiac disorders	—	—
Diverticulitis	Infections and infestations	—	—
Diverticulum	Gastrointestinal disorders	—	—
Duodenal ulcer haemorrhage	Gastrointestinal disorders	—	—
Endometrial hyperplasia	Reproductive system and breast disorders	—	—
Escherichia bacteraemia	Infections and infestations	—	—
Facial bones fracture	Injury, poisoning and procedural complications	—	—
Fall	Injury, poisoning and procedural complications	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Haemorrhage intracranial	Nervous system disorders	—	—
Hand fracture	Injury, poisoning and procedural complications	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	—	—
Invasive lobular breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Lipase increased	Investigations	—	—
Lipoma excision	Surgical and medical procedures	—	—
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Other adverse events (24 terms — click to expand)

Reaction	System	Liraglutide 3.0 mg	Placebo
Nausea	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Vomiting	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Constipation	Gastrointestinal disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Influenza	Infections and infestations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Gastroenteritis	Infections and infestations	—	—
Fatigue	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Sinusitis	Infections and infestations	—	—

Most-reported serious reactions: Atrial flutter, Osteoarthritis, Adenocarcinoma pancreas, Amylase increased, Angina pectoris, Atrial fibrillation, Cardiac failure congestive, Cellulitis.

Data from ClinicalTrials.gov NCT02963922 adverse events section.

Sponsor's own description

This trial is conducted globally. The aim of this trial is to investigate effect and safety of liraglutide 3.0 mg in subjects with overweight or obesity and type 2 diabetes mellitus treated with basal insulin.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial.
   Garvey WT, Birkenfeld AL, Dicker D, Mingrone G, et al · · 2020 · cited 120× · PMID 32139381 · DOI 10.2337/dc19-1745
2. Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials.
   Hu W, Song R, Cheng R, Liu C, et al · · 2022 · cited 72× · PMID 35898463 · DOI 10.3389/fendo.2022.927859
3. Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis.
   Smith I, Hardy E, Mitchell S, Batson S. · · 2022 · cited 15× · PMID 36569429 · DOI 10.2147/dmso.s392952
4. Medicines for Obesity: Appraisal of Clinical Studies with Grading of Recommendations, Assessment, Development, and Evaluation Tool.
   Karavia EA, Giannopoulou PC, Konstantinopoulou V, Athanasopoulou K, et al · · 2023 · cited 3× · PMID 36771314 · DOI 10.3390/nu15030606