Liraglutide

What it is

Liraglutide is an acylated GLP-1 analogue with 97% amino acid homology to native GLP-1. It acts as a GLP-1 receptor agonist, producing glucose-dependent increases in insulin secretion, decreasing glucagon secretion, causing minor delays in gastric emptying, and reducing appetite and energy intake. The mechanism of protraction relates to slowed release from the injection site and a reduced elimination rate owing to metabolic stabilisation and reduced renal filtration. Liraglutide likely induces satiety through activation of areas in the hindbrain and possibly by preserving free leptin levels. It also influences neuroplasticity, synaptic remodeling, and neuroinflammatory processes, and has been shown to activate AMPK, enhance lipophagy, and restore lipid homeostasis in vitro. In islets, liraglutide increases beta-cell Ca²⁺ oscillation frequency partly via activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, augmenting insulin secretion. Cardiovascular protective effects include inhibition of oxidative stress, reduction of vascular endothelial dysfunction, modulation of macrophage polarization, and suppression of inflammatory pathways such as PI3K/AKT and NF-κB (PMIDs: 36771035, 38548245, 40784419).

Class: Glucagon-like peptide-1 (GLP-1) receptor agonist; incretin mimetic; acylated GLP-1 analogue with 97% amino acid homology with native GLP-1

What it's studied for

• Type 2 diabetes mellitus — glycemic control Human RCT
  • Once-daily liraglutide 1.2 mg subcutaneous reduced HbA1c by 1.0% and body weight by 1.9 kg over 30 weeks as add-on to 1–3 oral antidiabetic drugs in adults with T2DM, though inferior to semaglutide 1.0 mg weekly. PMID 31539622 Capehorn et al., Diabetes & Metabolism (2020) — SUSTAIN 10 trial
  • Pharmacodynamic studies confirmed liraglutide improves fasting and postprandial glycemic control via glucose-dependent insulin increase and glucagon reduction; low risk of hypoglycemia. PMID 26597252 Jacobsen et al., Clinical Pharmacokinetics (2016)
• Obesity and weight management (adults) Human RCT
  • Subcutaneous liraglutide 3 mg once daily indicated for chronic weight management in adults with BMI ≥30 or ≥27 with comorbidity. Phase III trials (32 or 56 weeks) showed clinically relevant reductions in body weight and waist circumference; generally well tolerated. PMID 25985864 Scott, Drugs (2015)
  • Liraglutide 3.0 mg/day resulted in 5.9–8.0% weight reduction over 56 weeks; placebo-subtracted loss 3.9–6.0%. ≥5% weight loss achieved by 50–76% of treated patients. PMID 26074046 Christou et al., Current Vascular Pharmacology (2016)
  • Meta-analysis (5 RCTs, 4,754 patients): liraglutide produced mean weight loss of -5.52 kg vs placebo in obese, non-diabetic individuals; OR for >5% body weight loss 5.46 (95% CI 3.57–8.34). PMID 32127832 Zhang et al., African Health Sciences (2019)
  • Meta-analysis in prediabetes: liraglutide reduced body weight (MD -4.95 kg), BMI (MD -2.06 kg/m²), waist circumference (MD -4.61 cm), and HbA1c (MD -0.33%) vs control. PMID 38782201 Alsanea et al., Endocrine Practice (2024)
  • NMA of 6 RCTs: all tirzepatide doses associated with statistically greater weight reduction vs liraglutide 3 mg; all interventions had comparable safety profiles. PMID 41820778 Ciudin et al., Advances in Therapy (2026) — Bayesian NMA
• Weight management in children and adolescents Human RCT
  • Meta-analysis of 7 RCTs (547 participants): liraglutide reduced body weight (WMD -2.13 kg), BMI (WMD -1.56 kg/m²), BMI SDS (WMD -0.17), HbA1c (WMD -0.29%), and fasting glucose vs placebo. No significant difference in frequency of adverse events vs placebo. PMID 37672063 Gou et al., European Journal of Pediatrics (2023)
  • Population PK analysis: body weight was the main covariate affecting liraglutide exposure; exposure-response relationship demonstrated in adolescents and adults similarly. PMID 33963681 Carlsson Petri et al., Pediatric Obesity (2021)
• Obesity management after bariatric surgery (poor response / weight regain) Human observational
  • Retrospective cohort (119 patients) + meta-analysis: liraglutide 3 mg produced mean weight loss of 5.6% at 12 weeks and 9.3% at 24 weeks in adults with insufficient weight loss or regain after bariatric surgery. No serious side effects reported. PMID 38183597 Vinciguerra et al., Obesity Surgery (2024)
• Obesity with comorbid stable bipolar disorder Human RCT
  • 40-week RCT (n=60): liraglutide 3 mg/day vs placebo in stable bipolar disorder with obesity/overweight. Liraglutide associated with significantly greater reductions in body weight, BMI, HbA1c, binge eating, and hunger. Well tolerated. PMID 38227621 McElroy et al., Journal of Clinical Psychopharmacology (2024)
• Polycystic ovary syndrome (PCOS) — metabolic and reproductive outcomes Mixed
  • Double-blind RCT (72 women, 26 weeks): liraglutide 1.8 mg/day caused 5.2 kg weight loss vs placebo; improved bleeding ratio, increased SHBG, decreased free testosterone, reduced ovarian volume. Nausea and constipation more prevalent with liraglutide. PMID 28479118 Nylander et al., Reproductive Biomedicine Online (2017)
  • Open-label RCT (60 women, 12 weeks): subcutaneous liraglutide 1.2 mg/day reduced body weight, BMI, visceral fat, body fat percentage, and free testosterone vs metformin alone; combination was more effective than either alone for some endpoints. PMID 41384017 Long et al., Frontiers in Endocrinology (2025)
  • Meta-analysis of 12 RCTs (1,096 patients): liraglutide + metformin superior to metformin alone for BMI, glucose, lipids, hormone levels, menstrual cycle establishment, ovulation rate, and spontaneous conception. Higher incidence of gastrointestinal reactions in combination group. PMID 40481408 Huang & He, BMC Women's Health (2025)
  • Meta-analysis (6 studies, 401 women): liraglutide monotherapy or add-on therapy significantly reduced waist circumference (-6.28 cm), BMI (-2.53 kg/m²), and weight (-4.33 kg) over 12–24 weeks in obese women with PCOS. HOMA-IR moderately improved. PMID 33555153 Tian et al., Minerva Medica (2022)
• Peripheral artery disease in type 2 diabetes Human RCT
  • RCT (55 participants, 18-month follow-up): liraglutide up to 1.8 mg/day significantly improved transcutaneous oxygen pressure vs control (ETD +10.9 mmHg), reduced urine albumin-to-creatinine ratio, CRP, IL-6, and increased circulating progenitor and endothelial progenitor cells and VEGF-A. PMID 40276845 Caruso et al., Diabetes, Obesity & Metabolism (2025) — STARDUST trial
• Non-alcoholic fatty liver disease (NAFLD) Mixed
  • Meta-analysis of 5 RCTs (371 participants): liraglutide produced non-significant reductions in hepatic fat content and ALT vs control. Significant reduction in BMI (driven by T2DM subgroup) and triglycerides. Increased gastrointestinal adverse events. Authors concluded current data do not substantiate liraglutide use i PMID 33309563 Kalogirou et al., Clinics and Research in Hepatology and Gastroenterology (2021)
• Diabetic nephropathy Mixed
  • Meta-analysis of 18 RCTs (1,580 patients): liraglutide reduced UACR, serum creatinine, cystatin C, blood glucose (FBG, PBG, HbA1c), BMI, and inflammatory markers (TNF-α, IL-6) in T2DM nephropathy patients vs control. No significant difference in BUN or eGFR. PMID 35392872 Mali et al., BMC Endocrine Disorders (2022)
• Obstructive sleep apnea Human RCT
  • 32-week double-blind RCT (n=359, non-diabetic adults): liraglutide 3.0 mg reduced AHI by -12.2 vs -6.1 events/h for placebo (ETD -6.1, P=0.015), produced greater weight loss (-5.7% vs -1.6%), and greater reductions in HbA1c and SBP. PMID 27005405 Blackman et al., International Journal of Obesity (2016) — SCALE Sleep Apnea RCT
• Visceral and ectopic fat reduction Human RCT
  • Meta-analysis of 16 RCTs (845 participants): liraglutide significantly decreased visceral fat (SMD -0.72), liver fat (SMD -0.78), and BMI vs control. Adequate dosage (≥1.8 mg/day) and duration (16–40 weeks) were decisive factors for visceral fat reduction. Mild gastrointestinal reactions were the main adverse event. PMID 36314246 He et al., Diabetes, Obesity & Metabolism (2023)
• Blood pressure reduction Human RCT
  • Meta-analysis of 18 RCTs (7,616 liraglutide; 6,046 control): liraglutide reduced SBP by 3.18 mmHg vs placebo; no significant effect on DBP overall. Liraglutide 3.0 mg/d significantly reduced DBP by 1.46 mmHg; effect on SBP not significant when intervention lasted >1 year. PMID 30616638 Zhao et al., BMC Endocrine Disorders (2019)
  • Meta-analysis of 10 RCTs (968 patients with T2DM): liraglutide 1.8 mg/day reduced SBP by -5.39 mmHg and body weight by -2.07 kg vs placebo. Heart rate increased by 6.03 bpm vs placebo. No significant diastolic BP difference. PMID 31610701 Zhao et al., Clinical and Experimental Hypertension (2020)
• Cardiovascular protection / outcomes in type 2 diabetes Human RCT
  • Review of LEADER CVOT: liraglutide became the second modern glucose-lowering agent to demonstrate significant cardiovascular benefit in T2DM patients with high CV risk. Authors note uncertainty whether results are generalizable to all T2DM patients. PMID 28387138 Chudleigh & Bain, Expert Opinion on Drug Safety (2017) — LEADER trial review
• Type 1 diabetes — adjunct to insulin Human RCT
  • 52-week double-blind RCT (1,398 adults with T1DM): liraglutide 1.8 mg and 1.2 mg added to insulin reduced HbA1c, total insulin dose, and body weight vs placebo. Increased rates of symptomatic hypoglycemia and hyperglycemia with ketosis (significant for 1.8 mg only), limiting clinical use. PMID 27506222 Mathieu et al., Diabetes Care (2016) — ADJUNCT ONE trial
• Neurological/neuroprotective effects (Alzheimer's disease, cerebral ischemia) Animal studies only
  • Review: liraglutide reduced ischemia area caused by MCAO in animal models, limited neurological deficits, demonstrated anti-apoptotic effects, reduced free radical levels, and showed potential effects on amyloid-beta trafficking relevant to Alzheimer's disease. All data preclinical. PMID 30823403 Wiciński et al., International Journal of Molecular Sciences (2019)
• Depressive symptoms / psychiatric disorders Animal studies only
  • Review: liraglutide modulates mood-related neural circuits, neuroplasticity, synaptic remodeling, and neuroinflammation. Evidence described as preliminary; mechanistic distinctions from conventional antidepressants noted. No large-scale clinical trial data cited. PMID 40471368 Gammoh et al., Molecular Biology Reports (2025)
  • Review: preliminary clinical evidence suggests liraglutide may decrease weight gain, improve cognition, and prevent cognitive decline. Considerable preclinical data on neurogenesis promotion, anti-apoptosis, and antioxidant effects. PMID 30020885 Camkurt et al., Hormone Molecular Biology and Clinical Investigation (2018)
• Diabetic wound healing Animal studies only
  • Animal study (db/db and STZ-induced diabetic mice): liraglutide significantly accelerated wound closure via the Myo1c/Dock5 pathway, improving re-epithelialization, collagen deposition, and keratinocyte function. PMID 39159301 Zhang et al., Advanced Science (2024)
• Diabetic cardiomyopathy Animal studies only
  • Review: liraglutide demonstrated antioxidant, antihyperglycemic, anti-apoptotic, and anti-inflammatory effects in diabetic cardiomyopathy models. Evidence primarily from preclinical studies. PMID 37966282 Gupta & Ekbbal, Current Drug Research Reviews (2024)
• Renal ischemia-reperfusion injury Animal studies only
  • C57BL/6J mouse model (72 mice, 8/group): liraglutide relieved renal ischemia-reperfusion injury and ferroptosis, inhibited macrophage extracellular trap formation, and skewed macrophage polarization to M2 phenotype via STAT3/6 pathway. PMID 39340991 Sun et al., International Immunopharmacology (2024)
• Hepatic steatosis / NAFLD (mechanistic/preclinical) Animal studies only
  • Mouse model (HFD, 12 weeks): liraglutide alleviated liver steatosis via RORα-mediated autophagy pathway; effect absent in liver-specific Rorα knockout mice. PMID 37310057 Yu et al., IUBMB Life (2023)
  • db/db mouse model: liraglutide (200 µg/kg/day i.p., 5 weeks) decreased hepatic iron deposition and ferroptosis, reduced AST/ALT and liver fibrosis, and suppressed ROS via Nrf2/HO-1/GPX4 pathway. PMID 35311455 Song et al., Bioengineered (2022)
• Aortic aneurysm and dissection Animal studies only
  • APOE-/- mouse model with Ang II infusion: liraglutide 200 µg/kg i.p. reduced aortic aneurysm/dissection incidence and mortality by inhibiting M1 macrophage polarization via GLP-1R/PI3K/AKT/CXCL3 pathway. PMID 38548245 Zhang et al., Biochemical Pharmacology (2024)
• Myocardial ischemia/reperfusion injury In vitro only
  • H9C2 cardiomyocyte cell line under hypoxia/reoxygenation: liraglutide preconditioning reduced cell death and intracellular calcium overload via Homer1-dependent regulation of ER calcium homeostasis. PMID 33535171 Cui et al., Aging (2021)
• Age-related macular degeneration (AMD) / retinal pigment epithelium protection In vitro only
  • ARPE-19 cell line: liraglutide reduced FFA-induced lipid droplet accumulation, oxidative stress, and EMT via AMPK activation and lipophagy enhancement. PMID 40332323 Tsou et al., International Journal of Molecular Sciences (2025)
• Intrauterine adhesions Animal studies only
  • IUA rat model and human endometrial organoids: liraglutide reduced endometrial inflammation, collagen fibrosis, and EMT by directly targeting NF-κB and inhibiting NF-κB phosphorylation. PMID 40784419 Shi et al., Experimental Cell Research (2025)
• Diabetic kidney disease — gut microbiome axis Animal studies only
  • DKD rat model: liraglutide 0.4 mg/kg/day improved renal tubule structure, altered gut microbiota composition, and increased serum L-5-Oxoproline levels, which reduced ectopic lipid deposition in renal tubular cells in a dose-dependent manner. PMID 39154828 Yi et al., European Journal of Pharmacology (2024)
• Sleep — increase in NREM sleep Animal studies only
  • Rat study: subcutaneous liraglutide (0.06, 0.10, 0.30, 0.60 mg/kg) dose-dependently decreased wakefulness and increased NREM sleep, primarily during the dark (active) period, at doses known to reduce heroin-seeking behavior. PMID 36410565 Fang et al., Brain Research Bulletin (2023)
• PCOS — follicle development and ovulation Animal studies only
  • RNA-sequencing of granulosa cells from PCOS patients treated with liraglutide showed inhibition of CXCL10 secretion via JAK signaling. In vitro mouse follicle culture: liraglutide improved follicular development and ovulation disrupted by CXCL10. PMID 39107809 Zhao et al., Reproductive Biology and Endocrinology (2024)

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.