Mounjaro, Zepbound
Evidence Grade A — Regulatory approved. 1852 published studies. 215 registered clinical trials.
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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.
1,852 published studies: 1002 human, 58 animal, 34 in-vitro, 659 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.
Tirzepatide for the Treatment of Concurrent Type 1 Diabetes and Overweight or Obesity
Trial of Tirzepatide for the Treatment of Cannabis Use Disorder
Safety and Efficacy of NA-931 and Tirzepatide in Adults Who Are Overweight or Obese
A Study of Weight Loss Intervention With Tirzepatide and Progestin Intrauterine Device to Treat Endometrial Hyperplasia and Grade 1 Endometrial Cancer
Tirzepatide for the Treatment of Cannabis Use Disorder
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Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
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.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
