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Retatrutide is a novel triple-receptor agonist that has already been tested in a couple of studies (phase 1 and phase 2) regarding its potential metabolic effects compared to previous incretin mimetics. Here is what researchers should know about these notable trials: The phase 1 study, conducted in Singapore in 2019, was the initial proof-of-concept investigation for retatrutide. It involved 47 healthy participants with a wide range of BMIs. The peptide was tested in dosages of up to 6mg/weekly for up to 12 weeks and was well tolerated amongst all participants. There was a significant reduction in appetite and improvements in metabolic parameters such as cholesterol levels [6]. Even the lowest dose of 1mg/weekly resulted in an 8.7% reduction in baseline weight, compared to a 2.1% reduction in the placebo group. The 12mg/weekly group saw the highest 24.2% reduction and 100% of the subjects receiving this dose lost at least 5% of baseline body weight. Additionally, there were significant reductions in waist circumference, blood pressure, glycated hemoglobin (HbA1c), fasting glucose and insulin levels, and non-HDL cholesterol levels [8].

Research regarding the potential weight loss effects of cagrilintide in people with obesity (but without T2D) includes notable phase 1b and phase 2 clinical trials, while phase 3 trials are currently underway. The phase 1b trial involved 96 non-diabetic adults aged 18-55 with overweight or obesity and lasted for 20 weeks. The study included six sequential, overlapping cohorts receiving varying weekly doses of cagrilintide (0.16 to 4.5 mg), combined with 2.4 mg semaglutide. Control groups received only semaglutide as an active comparator alongside placebo injections. The researchers reported the following findings [10]: The 2.4 mg/weekly cagrilintide + semaglutide group experienced a -17.1% weight reduction compared to -9.8% in the matched placebo plus semaglutide group (a difference of -7.3%). The 4.5 mg/weekly cagrilintide + semaglutide group achieved a -15.4% weight reduction versus -8% in the matched placebo group (a difference of -7.4%). The phase 2 trial involved 706 non-diabetic participants with overweight or obesity. Participants were randomized to receive various weekly doses of cagrilintide (0.3 mg to 4.5 mg/weekly), a daily dose of another FDA-approved GLP-1 agonist with a shorter half-life called liraglutide (3 mg/daily), or a placebo. Cagrilintide led to dose-dependent weight loss over 26 weeks, with reductions ranging from -6% to -10.8%, compared to -3% with placebo and -9% with liraglutide [11].