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Lir7.5
Liraglutide Research
Mostly mechanism / observationalLimited safety
12 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Liraglutide studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2009–2022 with a typical study size of 846 participants.
Based on 12 studies · 3 meta-analyses · 9 RCTs · 17,642 total participants
Confidence
High
By outcome
Blood sugar & glycemic control
Mostly mechanism / observational10 studies
Weight management
Mostly mechanism / observational7 studies
Safety & adverse effects
Mostly mechanism / observational7 studies
Cardiovascular outcomes
Mostly mechanism / observational4 studies
Liver & NASH
Too few graded studies2 studies
Slowing down
Only 1 study in the last 5 years · Latest meta-analysis: 2022
200920152022
1RCTn=9,340 · very large study2016
The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% CI, 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority).
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee. · N Engl J Med (2016)
Double-blind cardiovascular-outcomes RCT: 9,340 patients with type 2 diabetes and high cardiovascular risk, liraglutide (up to 1.8 mg/day) vs placebo, median follow-up 3.8 years
First major adverse cardiovascular event (CV death, nonfatal MI, or nonfatal stroke) reduced 13% (HR 0.87; 95% CI 0.78-0.97; P=0.01 for superiority)
Cardiovascular death lower with liraglutide (4.7% vs 6.0%; HR 0.78) and all-cause death lower (8.2% vs 9.6%; HR 0.85)
At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% CI, -6.0 to -5.1; P<0.001).
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DCW, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JPH; SCALE Obesity and Prediabetes NN8022-1839 Study Group. · N Engl J Med (2015)
56-week double-blind RCT in 3,731 adults WITHOUT type 2 diabetes (BMI ≥30, or ≥27 with comorbidities), liraglutide 3.0 mg/day vs placebo plus lifestyle (2:1)
Mean weight loss 8.4 kg (liraglutide) vs 2.8 kg (placebo); difference -5.6 kg (P<0.001)
≥5% weight loss in 63.2% vs 27.1%; >10% loss in 33.1% vs 10.6% (both P<0.001)
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%]).
The time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13-0·34).
le Roux CW, Astrup A, Fujioka K, Greenway F, Lau DCW, Van Gaal L, Ortiz RV, Wilding JPH, Skjøth TV, Manning LS, Pi-Sunyer X; SCALE Obesity Prediabetes NN8022-1839 Study Group. · Lancet (2017)
160-week (3-year) double-blind RCT: 2,254 adults with prediabetes and obesity, liraglutide 3.0 mg vs placebo (2:1)
Progression to type 2 diabetes markedly delayed: HR 0.21 (95% CI 0.13-0.34); 2% vs 6% diagnosed while on treatment
Greater sustained weight loss at week 160 (-6.1% vs -1.9%; difference -4.3%; P<0.0001)
At 52 weeks, HbA1c decreased by 0.51% with glimepiride, compared with 0.84% with liraglutide 1.2 mg (difference -0.33%; p=0.0014) and 1.14% with liraglutide 1.8 mg (-0.62; p<0.0001).
Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. · Lancet (2009)
52-week double-blind, double-dummy active-controlled RCT: 746 patients with early type 2 diabetes, liraglutide 1.2 or 1.8 mg vs glimepiride 8 mg monotherapy
HbA1c fell more with liraglutide 1.8 mg (-1.14%) than glimepiride (-0.51%); difference -0.62% (P<0.0001)
Liraglutide produced greater reductions in weight and blood pressure and less hypoglycemia than glimepiride
A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%).
Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S; NN8022-4180 Trial Investigators. · N Engl J Med (2020)
56-week phase-3 double-blind RCT in 251 adolescents (12 to <18 years) with obesity and poor response to lifestyle therapy, liraglutide 3.0 mg vs placebo (1:1)
Liraglutide superior on BMI standard-deviation score change at week 56 (estimated difference -0.22; P=0.002)
≥5% BMI reduction in 43.3% vs 18.7%; ≥10% in 26.1% vs 8.1%; body weight -4.50 kg vs placebo
When added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of beta-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia.
Buse JB, Sesti G, Schmidt WE, Montanya E, Chang CT, Xu Y, Blonde L, Rosenstock J; Liraglutide Effect Action in Diabetes-6 Study Group. · Diabetes Care (2010)
14-week extension of the head-to-head LEAD-6 RCT comparing once-daily liraglutide 1.8 mg with twice-daily exenatide 10 µg added to oral antidiabetic agents
In the core trial liraglutide improved HbA1c, fasting glucose, and beta-cell function (HOMA-B) more than exenatide, with less persistent nausea and hypoglycemia
Switching from exenatide to liraglutide further reduced HbA1c (-0.32%), fasting glucose, weight (-0.9 kg), and systolic blood pressure (-3.8 mmHg)
Liraglutide 1.8 mg reduced ALT in these patients vs. placebo (-8.20 vs. -5.01 IU/L; P = 0.003)... This effect was lost after adjusting for liraglutide's reduction in weight and HbA1c.
In terms of efficacy, semaglutide 2.4mg (-12.47 kg) had the best weight loss, followed by liraglutide 3.0mg (-5.24 kg), semaglutide 1.0mg (-3.74 kg) and liraglutide 1.8 mg (-3.29 kg).
Xie Z, Yang S, Deng W, Li J, Chen J. · Clin Epidemiol (2022)
Network meta-analysis of 23 RCTs (11,545 patients) of liraglutide and semaglutide monotherapy for weight loss in obesity/overweight
Liraglutide 3.0 mg produced -5.24 kg weight loss vs placebo — effective, but less than semaglutide 2.4 mg (-12.47 kg)
Liraglutide 1.8 mg reduced HbA1c by -1.23% (95% CI -1.66 to -0.80) vs placebo
GLP-1 analogues reduce hepatic steatosis, concentrations of liver enzymes, and insulin resistance... we assessed the safety and efficacy of the long-acting GLP-1 analogue, liraglutide, in patients with non-alcoholic steatohepatitis.
Multicentre double-blind phase-2 RCT in 52 overweight patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH), liraglutide 1.8 mg/day vs placebo for 48 weeks
Primary outcome was histological resolution of definite NASH without worsening fibrosis on end-of-treatment biopsy
Resolution of definite NASH without worsening fibrosis occurred in 9 of 23 (39%) on liraglutide vs 2 of 22 (9%) on placebo (relative risk 4.3, 95% CI 1.0-17.7; p=0.019)
Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus.
Kang YM, Cho YK, Lee J, Lee SE, Lee WJ, Park JY, Kim YJ, Jung CH, Nauck MA. · Diabetes Metab J (2019)
Meta-analysis of three cardiovascular-outcome trials of long-acting GLP-1 receptor agonists: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly)
Pooled, the class significantly reduced three-point MACE (CV death, nonfatal MI, nonfatal stroke) and cardiovascular death
Places liraglutide's LEADER benefit in the context of a consistent class effect on cardiovascular outcomes