Key papers ✓ 7~ 1

• ✓ Positive human RCTLancet · 2017

  3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.

  Humans2,254 peopleRandomizedPlacebo-controlledDouble-blind160 weeks

  Randomised, double-blind, placebo-controlled trial (SCALE Obesity and Prediabetes, 3-year assessment)

  In 2254 adults with obesity and prediabetes, 3 years of liraglutide 3.0 mg reduced weight by 6.1% vs 1.9% and lowered diabetes onset (2% vs 6%; HR 0.21), though about half of participants withdrew.

  Key resultDiabetes diagnosed in 26 (2%) of 1472 on liraglutide vs 46 (6%) of 738 on placebo; time to onset 2.7 times longer (95% CI 1.9 to 3.9, p<0.0001), hazard ratio 0.21 (0.13-0.34)

  Study details

  Studied

  Adults with prediabetes and BMI of at least 30, or at least 27 with comorbidities

  Compared with

  Matched placebo, with reduced-calorie diet and exercise

  Main outcome

  Time to onset of type 2 diabetes

  Sample

  2254 randomized 2:1 (1505 liraglutide, 749 placebo)

  Authors' conclusion

  Liraglutide 3.0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes.

  Limitations

  About half withdrew (50% completed); withdrawn individuals were not followed up after discontinuation.

  DOI 10.1016/S0140-6736(17)30069-7PubMed 28237263
• ~ Mixed human RCTJAMA · 2022

  Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.

  Humans338 peopleRandomizedPlacebo-controlledDouble-blind68 weeks

  Randomized, open-label (active arms double-blinded against placebo), phase 3b trial at 19 US sites

  In 338 adults with obesity, liraglutide reduced weight by 6.4% at 68 weeks vs 1.9% with placebo but much less than semaglutide (15.8%); 27.6% stopped liraglutide and GI events affected 82.7%.

  Key resultWeight change -15.8% with semaglutide vs -6.4% with liraglutide (difference -9.4 percentage points, 95% CI -12.0 to -6.8; P < .001); pooled placebo -1.9%

  Study details

  Studied

  Adults with overweight or obesity, without diabetes

  Compared with

  Once-daily liraglutide 3.0 mg (and pooled placebo)

  Main outcome

  Percentage change in body weight

  Sample

  338 randomized (semaglutide n=126, liraglutide n=127, pooled placebo n=85)

  Authors' conclusion

  Once-weekly semaglutide 2.4 mg resulted in significantly greater weight loss at 68 weeks than once-daily liraglutide 3.0 mg, added to diet and activity counseling.

  Limitations

  Semaglutide vs liraglutide comparison was open-label.

  DOI 10.1001/jama.2021.23619PubMed 35015037Free full text
• ✓ Positive human RCTN Engl J Med · 2020

  A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind56 weeks treatment plus 26 weeks follow-up

  Randomized, double-blind trial with 56-week treatment and 26-week follow-up

  In 251 adolescents with obesity, 56 weeks of liraglutide lowered BMI SD score vs placebo (-0.22) and body weight by about 5 percentage points; GI events 64.8% vs 36.5% and BMI rose again after stopping.

  Key resultBMI SD score difference -0.22 (95% CI -0.37 to -0.08; P = 0.002) favoring liraglutide; BMI reduction of at least 5% in 43.3% vs 18.7%

  Study details

  Studied

  Adolescents (12 to <18 years) with obesity and poor response to lifestyle therapy

  Compared with

  Placebo plus lifestyle therapy

  Main outcome

  Change in BMI standard-deviation score at week 56

  Sample

  125 assigned to liraglutide and 126 to placebo

  Authors' conclusion

  In adolescents with obesity, liraglutide 3.0 mg plus lifestyle therapy led to a significantly greater reduction in BMI SD score than placebo. GI adverse events were more frequent with liraglutide.

  Limitations

  BMI SD score rose more after discontinuation; more GI adverse events and discontinuations with liraglutide.

  DOI 10.1056/NEJMoa1916038PubMed 32233338
• ✓ Positive human RCTN Engl J Med · 2025

  Liraglutide for Children 6 to <12 Years of Age with Obesity - A Randomized Trial.

  Humans82 peopleRandomizedPlacebo-controlled56 weeks plus 26-week follow-up

  Phase 3a randomized trial (2:1), SCALE Kids

  In 82 children aged 6-11 with obesity, 56 weeks of liraglutide changed BMI by -5.8% vs +1.6% with placebo; GI adverse events 80% vs 54%.

  Key resultMean BMI change -5.8% with liraglutide vs 1.6% with placebo (difference -7.4 percentage points, 95% CI -11.6 to -3.2; P<0.001)

  Study details

  Studied

  Children aged 6 to <12 years with obesity

  Compared with

  Placebo plus lifestyle interventions

  Main outcome

  Percentage change in BMI

  Sample

  82 randomized (56 liraglutide, 26 placebo)

  Authors' conclusion

  Liraglutide for 56 weeks plus lifestyle interventions produced a greater BMI reduction than placebo in children with obesity. GI adverse events were more common with liraglutide.

  Limitations

  Small trial (82 children); GI adverse events more common (80% vs 54%).

  DOI 10.1056/NEJMoa2407379PubMed 39258838
• ✓ Positive human RCTN Engl J Med · 2021

  Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined.

  Humans195 peopleRandomizedPlacebo-controlled1 year

  Randomized, head-to-head, placebo-controlled trial of exercise, liraglutide, both, or placebo

  After an 8-week diet (13.1 kg lost), 195 adults on liraglutide kept off 6.8 kg more than placebo at 1 year, and liraglutide plus exercise did best; increased heart rate and gallstones were seen more with liraglutide alone.

  Key resultWeight loss vs placebo: exercise -4.1 kg (P = 0.03), liraglutide -6.8 kg (P<0.001), combination -9.5 kg (P<0.001)

  Study details

  Studied

  Adults with obesity (BMI 32 to 43) without diabetes

  Compared with

  Placebo plus usual activity

  Main outcome

  Change in body weight (primary), body-fat percentage

  Sample

  195 participants after an 8-week low-calorie diet, randomized to four arms

  Authors' conclusion

  A strategy combining exercise and liraglutide improved healthy weight loss maintenance more than either treatment alone.

  DOI 10.1056/NEJMoa2028198PubMed 33951361
• ✓ Positive human RCTInt J Obes (Lond) · 2016

  Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial.

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind32 weeks

  Randomized, double-blind trial (SCALE Sleep Apnea)

  In 359 adults with obesity and moderate-severe sleep apnea, 32 weeks of liraglutide reduced the apnea-hypopnea index by 12.2 vs 6.1 events/hour and weight by 5.7% vs 1.6%.

  Key resultAHI fell -12.2 vs -6.1 events/h; estimated difference -6.1 (95% CI -11.0 to -1.2), P=0.0150; weight -5.7% vs -1.6%

  Study details

  Studied

  Non-diabetic adults with obesity and moderate or severe obstructive sleep apnea unwilling/unable to use CPAP

  Compared with

  Placebo, with diet and exercise

  Main outcome

  Change in apnea-hypopnea index (AHI)

  Sample

  359 not stated; 180 liraglutide, 179 placebo

  Authors' conclusion

  Liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, systolic BP and HbA1c; weight loss improves OSA-related parameters.

  Limitations

  Association of weight loss with OSA improvement was post hoc.

  DOI 10.1038/ijo.2016.52PubMed 27005405Free full text
• ✓ Positive human RCTN Engl J Med · 2019

  Liraglutide in Children and Adolescents with Type 2 Diabetes.

  Humans135 peopleRandomizedPlacebo-controlledDouble-blind26 weeks double-blind, 52 weeks total

  Randomized, double-blind 26-week period plus 26-week open-label extension

  In 134 youths with type 2 diabetes on metformin, liraglutide lowered HbA1c by 1.06 points more than placebo at 26 weeks (1.30 at 52 weeks), with more GI adverse events.

  Key resultHbA1c fell 0.64 percentage points with liraglutide and rose 0.42 with placebo (difference -1.06, P<0.001)

  Study details

  Studied

  Patients aged 10 to <17 years with type 2 diabetes on metformin (with or without insulin)

  Compared with

  Placebo (all on metformin)

  Main outcome

  Change in HbA1c at 26 weeks

  Sample

  135 randomized; 134 treated (66 liraglutide, 68 placebo)

  Authors' conclusion

  Liraglutide up to 1.8 mg/day added to metformin improved glycemic control over 52 weeks, at the cost of more gastrointestinal adverse events.

  DOI 10.1056/NEJMoa1903822PubMed 31034184
• ✓ Positive human RCTLancet · 2016

  Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind48 weeks

  Multicentre, double-blind, randomised, placebo-controlled phase 2 trial (LEAN)

  In 52 patients with NASH, 48 weeks of liraglutide resolved NASH in 39% vs 9% with placebo, with less fibrosis progression (9% vs 36%); diarrhea, constipation and appetite loss were more frequent.

  Key resultNASH resolved in 9 (39%) of 23 on liraglutide vs 2 (9%) of 22 on placebo (relative risk 4.3, 95% CI 1.0-17.7; p=0.019)

  Study details

  Studied

  Overweight patients with clinical evidence of non-alcoholic steatohepatitis

  Compared with

  Placebo

  Main outcome

  Resolution of definite NASH without worsening fibrosis

  Sample

  52 not stated; 26 per arm randomized, 45 biopsied (23 liraglutide, 22 placebo)

  Authors' conclusion

  Liraglutide was safe, well tolerated and led to histological resolution of NASH, warranting extensive longer-term studies.

  Limitations

  Small phase 2 trial in four UK centres; GI side effects more common with liraglutide.

  DOI 10.1016/S0140-6736(15)00803-XPubMed 26608256

Reported side effects

• commonGastrointestinal events (nausea, diarrhea, constipation) [ref] [ref] [ref] [ref] [ref]
• commonLoss of appetite [ref]
• commonDiscontinuation due to adverse events [ref] [ref]
• commonSerious adverse events (similar to or slightly above placebo) [ref] [ref]
• reportedIncreased heart rate [ref]
• reportedGallstones (cholelithiasis) [ref]

Weight/BMI tends to rise again after stopping; one suicide in the adolescent trial was judged unlikely to be drug-related.

332 registered human trials (18 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.