CagriSema and the link between obesity and type 2 diabetes

Abstract

In The Lancet, Juan P Frias and colleagues report positive results in a phase 2 trial evaluating the safety and efficacy of co-administered cagrilintide and semaglutide (CagriSema) for type 2 diabetes, 1 Frias JP Deenadayalan S Erichsen L et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023; (published online June 23.)https://doi.org/10.1016/S0140-6736(23)01163-7 Google Scholar approximately 2 years after a phase 1b study showed early efficacy in the treatment of obesity. 2 Enebo LB Berthelsen KK Kankam M et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021; 397: 1736-1748 Summary Full Text Full Text PDF PubMed Google Scholar The role of a gut–brain axis in energy balance has been intensely studied since the 1994 discovery of leptin as a hormone produced by adipose tissue in response to feeding. 3 Zhang Y Proenca R Maffei M Barone M Leopold L Friedman JM Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372: 425-432 Crossref PubMed Scopus (11820) Google Scholar In the years that followed, many investigations led to the current understanding of energy regulation to include signalling in the liver and endocrine pancreas through both classic incretins (eg, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 [GLP-1]) and the unique hormone co-secreted with insulin (amylin). Research also showed that abnormal energy balance can be improved by perturbing the axis via altering or bypassing segments of the gastrointestinal tract with bariatric surgery. 4 Ashrafian H le Roux CW Metabolic surgery and gut hormones—a review of bariatric entero-humoral modulation. Physiol Behav. 2009; 97: 620-631 Crossref PubMed Scopus (88) Google Scholar And nearly 30 years later, gut hormone analogues, notably liraglutide, semaglutide, and tirzepatide, have been investigated as effective treatments for both type 2 diabetes and obesity. CagriSema is currently also being evaluated as a drug to treat both type 2 diabetes and obesity. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trialIn people with type 2 diabetes, treatment with CagriSema resulted in clinically relevant improvements in glycaemic control (including CGM parameters). The mean change in HbA1c with CagriSema was greater versus cagrilintide, but not versus semaglutide. Treatment with CagriSema resulted in significantly greater weight loss versus semaglutide and cagrilintide and was well tolerated. These data support further investigation of CagriSema in this population in longer and larger phase 3 studies. Full-Text PDF