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well tolerated

Most adverse events reported were mild or moderate in severity, and there were no apparent differences between treatment groups: events were reported in 69/71 participants taking 0.16-4.5 mg cagrilintide and 23/24 on placebo.

Two severe adverse events were reported in two participants, one with cagrilintide 1.2 mg in combination with semaglutide 2.4 mg (viral meningitis), and one in the pooled placebo in combination with semaglutide 2.4 mg group (serum creatinine increase). Both the events were deemed unlikely to be related to study treatment.

“Our data support the further clinical development of this drug combination for weight management. A phase 3 trial program is now being planned to test cagrilintide in combination with semaglutide for weight management,” they conclude.

No Clear Differences in Adverse Events Between Groups

Enebo and coauthors explain that cagrilintide is thought to affect food choices by targeting both homeostatic and hedonic regions of the brain to induce satiety.

“Mean body weight reductions in this trial were also greater than those found in 26 weeks with cagrilintide alone (up to 7.8% reduction in body weight relative to placebo with 4.5-mg dose),” add the authors, referring to previous research.

“The data support once-weekly dosing. The combination of cagrilintide 1.2, 2.4, or 4.5 mg plus semaglutide 2.4 mg led to greater weight loss compared with semaglutide 2.4 mg only.”

For the current study, conducted in the United States, 96 individuals, of whom 95 were exposed to treatment, aged 18-55 years with a BMI of 27.0-39.9 kg/m² who were otherwise healthy were randomized to cagrilintide (0.16-2.4 mg, n = 12 in each group; 4.5 mg group, n = 11) or placebo (n = 24) in combination with semaglutide 2.4 mg. Mean age was 40.6 years, 59% of participants were men, and 54% were Black or African American.

I agree with Prof Aronson completely. The way well-tolerated is used can be the scientific equivalent of political spin. Whether or not a patient has tolerated a drug is dependent of how tolerant the patient is (to adverse effects) as well as the adverse effects themselves, and is likely to be a function of the perceived benefits. A drug that prevents imminent death is likely to be tolerated even if it does cause your hair to fall out. On the other hand the same adverse event would not be tolerated for drug treatment of a mild headache. Toleration is an individual value judgement, and so the extent to which a patient has “tolerated” a drug can only be established by asking the patient. If a drug is described as well-tolerated the editors should expect some evidence that the patients have been asked appropriate questions about their experience of taking the drug. In the absence of such evidence the term should not be used.

It’s not obvious, but “tolerance” comes from the Latin word ferre, to carry, whose principal parts, from different roots, are ferro, ferre, tuli, latum (see BMJ 2000;320:625). And “tolerance” carries several technical meanings.

On the other hand, I’m not sure about tolerance either.

Pharmacological tolerance can be acquired or natural. Acquired tolerance is reduced sensitivity to a drug, from previous exposure either to it or (cross-tolerance) to another drug. It should not be confused with tachyphylaxis or …