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Researchers have investigated cagrilintide for managing blood sugar levels in patients with T2D (type 2 diabetes) when combined with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide. In a 32-week phase 2 trial, researchers evaluated the efficacy of a cagrilintide and semaglutide combination (marketed as CagriSema) for overweight and obese T2D patients. The scientists divided the subjects into three equal groups, each receiving either 2.4 mg/weekly semaglutide, 2.4 mg/weekly cagrilintide, or both doses combined (cagrilintide + semaglutide combo). The results were as follows [12]: Weight reduction was highest in the cagrilintide + semaglutide combo group (-15.6%), followed by cagrilintide alone (-8.1%) and semaglutide alone (-5.1%). HbA1c levels significantly decreased by -2.2% with the cagrilintide + semaglutide combo, -1.8% with semaglutide alone, and -0.9% with cagrilintide alone. Fasting glucose levels fell most significantly with the cagrilintide + semaglutide combo (-3.3 mmol/L), compared to semaglutide alone (-2.5 mmol/L) and cagrilintide alone (-1.7 mmol/L). As evident from the results, 2.4 mg/weekly cagrilintide proved more effective for weight reduction than 2.4 mg/weekly semaglutide. Moreover, cagrilintide significantly enhances the weight loss and antidiabetic properties of the GLP-1 agonist semaglutide.

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].