Evidence Grade A — Regulatory approved. 2040 published studies. 165 registered clinical trials.
Medically reviewed by a licensed medical professional
Loading...
Tirzepatide (sold as Mounjaro for diabetes and Zepbound for weight management) is a once-weekly injection that activates two gut hormone receptors simultaneously — GIP and GLP-1 — making it the first dual-action treatment in its class. It has produced the largest weight loss of any approved medication: an average of 22.5% body weight in clinical trials at the highest dose.
Tirzepatide is also known by these brand and alternate names:
2,040 published studies: 1096 human, 61 animal, 37 in-vitro, 729 reviews
Tirzepatide is marketed as Mounjaro for type 2 diabetes (approved May 2022) and Zepbound for weight management (approved November 2023), with a further approval for obstructive sleep apnoea in people with obesity (December 2024). It was developed by Eli Lilly and is the first medication to target both GIP and GLP-1 receptors.
In clinical trials, patients taking the highest dose lost an average of 22.5% of their body weight, and a head-to-head study showed it was significantly more effective than semaglutide for weight loss (20.2% versus 13.7%). A three-year extension study showed sustained weight loss of approximately 20% with continued use, and a separate trial found it reduced progression to type 2 diabetes by 94% in people with prediabetes. Trials are now underway for chronic kidney disease and cardiovascular outcomes. The most common side effects are gastrointestinal, including nausea and diarrhoea, which tend to improve over time.
Your body uses two key hormones after eating — GIP and GLP-1 — to control blood sugar and appetite. Most similar medications only target one of these. Tirzepatide is designed to activate both at the same time, which produces a combined effect greater than either hormone alone. It triggers insulin release when blood sugar is high, suppresses the hormone that raises blood sugar, slows stomach emptying so you feel full longer, and reduces appetite through signals to the brain. This dual approach is why it achieves greater weight loss and blood sugar improvements than single-target treatments.
Tirzepatide's clinical evidence is extensive. In a head-to-head study against semaglutide, it achieved 20.2% weight loss versus 13.7%. A three-year extension study showed sustained weight loss of approximately 20% with continued use. The SURMOUNT-3 trial found it reduced progression from prediabetes to type 2 diabetes by 94% — one of the most striking preventive results in metabolic medicine. It has also received approval for obstructive sleep apnoea in people with obesity. Active trials are investigating tirzepatide for chronic kidney disease and cardiovascular outcomes. A Phase II trial showed resolution of fatty liver disease (MASH) in 73% of patients at the highest dose. Side effects are predominantly gastrointestinal (nausea, diarrhoea, vomiting), tend to improve over time, and a thyroid tumour boxed warning exists based on animal data. Most weight is regained after stopping treatment, consistent with the class. A numerically higher rate of cardiovascular death was noted in one trial but was not statistically significant.
PeptideTrace tracks 165 registered clinical trials for Tirzepatide sourced from ClinicalTrials.gov.
Tirzepatide for the Treatment of Concurrent Type 1 Diabetes and Overweight or Obesity
Trial of Tirzepatide for the Treatment of Cannabis Use Disorder
Effectiveness of Combined GLP-1 Receptor Agonist Therapy and Structured Exercise on Skeletal Muscle Morphology, Quality, and Physical Function in Overweight and Obese Individuals
Safety and Efficacy of NA-931 and Tirzepatide in Adults Who Are Overweight or Obese
The Effect of Exercise and Tirzepatide on Weight and Health Outcomes (EXER-MED)
FDA ORIG 1
EMA Marketing Authorisation
FDA SUPPL 6
FDA SUPPL 2
FDA ORIG 1
FDA SUPPL 3
FDA SUPPL 19
FDA SUPPL 6
FDA SUPPL 15
FDA SUPPL 11
FDA SUPPL 5
FDA SUPPL 15
FDA SUPPL 22
FDA SUPPL 10
Health Canada Market Authorisation
FDA SUPPL 13
FDA SUPPL 20
FDA SUPPL 31
FDA SUPPL 31
FDA SUPPL 34
FDA SUPPL 39
FDA SUPPL 37
FDA SUPPL 41
FDA SUPPL 2
FDA SUPPL 9
FDA SUPPL 42
Tirzepatide is a 39-amino-acid synthetic peptide engineered as a dual GIP and GLP-1 receptor agonist. It contains a C20 unsaturated fatty diacid chain for albumin binding, producing a half-life of approximately 5 days and enabling once-weekly subcutaneous dosing. It is an imbalanced dual agonist with equal affinity for the GIP receptor relative to native GIP but approximately 5-fold weaker affinity at GLP-1R compared to native GLP-1.
Tirzepatide co-activates both GIPR and GLP-1R, producing synergistic enhancement of glucose-dependent insulin secretion, glucagon regulation, appetite suppression, and delayed gastric emptying. It displays biased agonism at GLP-1R, favoring cAMP signaling over β-arrestin recruitment, which may reduce receptor desensitization and improve sustained efficacy. The dual incretin mechanism engages non-overlapping hypothalamic and brainstem receptor populations, and GIP receptor activation may independently decrease food intake and increase energy expenditure. This dual agonism achieves greater metabolic effects than pure GLP-1 receptor agonism alone.
Tirzepatide is marketed as Mounjaro (type 2 diabetes, approved May 13, 2022), Zepbound (chronic weight management, approved November 8, 2023; moderate-to-severe OSA with obesity, approved December 2024). In the SURMOUNT-1 trial (N=2,539), tirzepatide 15 mg achieved 22.5% mean weight loss versus 2.4% with placebo over 72 weeks. SURMOUNT-5 showed superiority over semaglutide 2.4 mg (20.2% vs 13.7%). The SURPASS program demonstrated HbA1c reductions up to 2.30% with the 15 mg dose. In SURPASS-2, all tirzepatide doses were superior to semaglutide 1.0 mg for glycemic control. The SURPASS-CVOT trial (N=13,299) met noninferiority versus dulaglutide for cardiovascular outcomes but did not achieve superiority (MACE HR 0.92). The SUMMIT trial in heart failure with preserved ejection fraction showed a 38% reduction in cardiovascular death or worsening HF (HR 0.62).
Compare prices from 20 vendor listings
View pricing data across vendors and countries for Tirzepatide
Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
Evidence Reviews
Timelines
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
