Cagrilintide

Cagrilintide is a synthetic, long-acting analog of amylin. Amylin is a naturally occurring peptide
hormone released by the pancreas with insulin in response to food intake.

Here’s a breakdown of what cagrilintide does and its current status:

○ Mechanism of Action:

■ Cagrilintide activates both amylin and calcitonin receptors, offering a
distinct mechanism of action compared to other weight loss agents like
GLP-1 receptor agonists.
■ This dual receptor activity leads to increased satiety (feeling of fullness),
reduced food intake, and delayed gastric emptying.
■ Cagrilintide also plays a role in managing blood glucose levels by helping
to suppress glucagon, a hormone that raises blood sugar.
■ Its structure is modified from pramlintide, the backbone peptide, with
changes to enhance effectiveness, inhibit amyloid fibril formation, and
prolong its action.

○ Therapeutic Uses:
■ Cagrilintide is being investigated as a treatment for obesity and type 2
diabetes.
■ It is often studied in combination with semaglutide, a GLP-1 receptor
agonist, forming a co-formulation called CagriSema.
■ Early trials suggest it may also offer benefits for liver damage,
alcohol-related liver disease, and heart/blood vessel disease.

○ Clinical Trial Results (CagriSema):
■ CagriSema has entered Phase III clinical trials.
■ The REDEFINE 1 trial demonstrated significant weight loss in
obese/overweight individuals treated with CagriSema. Over 68 weeks,
participants experienced an average weight loss of 20.4%, compared to
3.0% with placebo.
■ The REDEFINE 2 trial in individuals with overweight or obesity and type 2
diabetes also showed substantial weight reduction with CagriSema,
nearly 16% in patients adhering to treatment.
■ Clinical trial data indicates CagriSema can also improve blood pressure,
waist circumference, lipid levels, and glycemic control.

○ Side Effects:
■ The most common side effects associated with cagrilintide are
gastrointestinal, including nausea, constipation, and diarrhea.
■ These side effects are similar to those seen with semaglutide alone and
tend to decrease over time.
■ Some patients describe a clear reduction in appetite without the intense
nausea sometimes associated with GLP-1 receptor agonists.