Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial.
OBJECTIVE
Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available.


OBJECTIVE
To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes.


METHODS
Fifty-six-week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%.


METHODS
Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (≥150 min/wk).


METHODS
Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56.


RESULTS
Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, -4.00% [95% CI, -5.10% to -2.90%]; liraglutide [1.8 mg] vs placebo, -2.71% [95% CI, -4.00% to -1.42%]; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 32.9% [95% CI, 24.6% to 41.2%]; for liraglutide [1.8 mg] vs placebo, 19.0% [95% CI, 9.1% to 28.8%]; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 18.5% [95% CI, 12.7% to 24.4%], P < .001; for liraglutide [1.8 mg] vs placebo, 9.3% [95% CI, 2.7% to 15.8%], P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported.


CONCLUSIONS
Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety.


BACKGROUND
clinicaltrials.gov Identifier:NCT01272232.
Diabetes Research Centre, University of Leicester, Leicester, United Kingdom.
Melanie J
MJ
Davies
International Diabetes Center, Park Nicollet Health Services, Minneapolis, Minnesota.
Richard
R
Bergenstal
Atlanta Diabetes Associates, Atlanta, Georgia.
Bruce
B
Bode
Northwestern University, Chicago, Illinois.
Robert F
RF
Kushner
National Research Institute, Los Angeles, California.
Andrew
A
Lewin
Novo Nordisk A/S, Søborg, Denmark.
Trine Vang
TV
Skjøth
Novo Nordisk A/S, Søborg, Denmark.
Arne Haahr
AH
Andreasen
Novo Nordisk A/S, Søborg, Denmark.
Christine Bjørn
CB
Jensen
Texas Diabetes Institute, San Antonio.
Ralph A
RA
DeFronzo
D000328:Adult; D000368:Aged; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004038:Diet, Reducing; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000188:drug therapy*; D015431:Weight Loss / Q000187:drug effects*
D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1