PMID-26132939 – SCALE Liraglutide Obesity and Prediabetes Trial
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22.
Quick Reference
| Property | Value |
|---|---|
| PMID | 26132939 |
| DOI | 10.1056/NEJMoa1411892 |
| Year | 2015 |
| Journal | The New England Journal of Medicine |
| Study Type | Randomized Controlled Trial (Multicenter, Double-Blind, Placebo-Controlled) |
| Evidence Level | I |
| Sample | n=3,731 adults with BMI >=30 or >=27 with comorbidities (without diabetes) |
| Peptide(s) Studied | Liraglutide |
Key Findings
- Mean weight loss at 56 weeks: Liraglutide 3.0 mg group lost -8.0% (+/-6.7%) of body weight vs -2.6% (+/-5.7%) in placebo (estimated treatment difference -5.4 kg; p<0.001)
- >=5% weight loss: 63.2% of liraglutide patients vs 27.1% placebo (p<0.001)
- >=10% weight loss: 33.1% of liraglutide patients vs 10.6% placebo (p<0.001)
- Prediabetes reversal: Among participants with prediabetes at baseline (n=2,254), liraglutide reduced progression to T2D by 80% over 3 years and reversed prediabetes to normoglycemia in a greater proportion
- Cardiometabolic markers: Significant improvements in waist circumference, blood pressure, fasting glucose, HbA1c, fasting insulin, lipids (total cholesterol, LDL, triglycerides), and hsCRP
- Quality of life: Greater improvement in physical functioning and overall health-related quality of life with liraglutide
- Adverse events: GI events (nausea 40.2% vs 14.7%, diarrhea 21.2% vs 14.9%, vomiting 16.3% vs 3.8%) were the most common; gallbladder-related events were more frequent with liraglutide
Study Design
Multicenter, double-blind, placebo-controlled RCT at 191 sites in 27 countries. Non-diabetic adults with BMI >=30 (or >=27 with dyslipidemia or hypertension) were randomized 2:1 to liraglutide 3.0 mg once daily subcutaneously or placebo, both combined with diet (-500 kcal/day deficit) and exercise (>=150 min/week). Liraglutide was titrated over 4 weeks (0.6 mg increments weekly). Co-primary endpoints: percent change in body weight, proportion achieving >=5% weight loss, and proportion achieving >10% weight loss at week 56.
Limitations
- 56-week duration — long-term efficacy and safety beyond 1 year not assessed in this trial (though weight regain after discontinuation is expected)
- High discontinuation rate (approximately 25% in both groups by week 56)
- Predominantly White population (approximately 78%) — may limit generalizability to other racial/ethnic groups
- Exclusion of patients with T2D limits applicability to that population (addressed in separate SCALE Diabetes trial)
- GI side effects may have unblinded some participants
- Post-trial weight regain was not systematically assessed
Clinical Relevance
SCALE Obesity and Prediabetes was the pivotal Phase III trial that supported FDA approval of Saxenda (liraglutide 3.0 mg) for chronic weight management in December 2014. The -8.0% mean weight loss significantly exceeded the FDA threshold for anti-obesity medication approval (>=5% placebo-subtracted or >=35% of patients achieving >=5% loss). The prediabetes-to-normoglycemia reversal finding provided important evidence for liraglutide's metabolic benefits beyond weight loss alone. While the magnitude of weight loss has since been surpassed by semaglutide 2.4 mg (-14.9% in STEP 1) and tirzepatide (-20.9% in SURMOUNT-1), SCALE established the GLP-1 receptor agonist class as a viable pharmacological approach to obesity.
Related
#research #RCT #liraglutide #evidence-level-I #metabolic