SUSTAIN-6 to SELECT — what worked for you?

From the other side of the consultation, briefly.

SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk. In 3,297 T2DM patients with high CV risk: MACE HR 0.74 (95% CI 0.58-0.95, p=0.02)[1].

Notable: the retinopathy signal in SUSTAIN-6 (HR 1.76) was subsequently attributed to rapid A1C reduction in patients with pre-existing retinopathy — not a direct drug effect. This has been confirmed in longer-term follow-up studies.

Dr.EndoIndy said:

SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.

Adding a me-too, because a thread of one person's experience is not much use.

Dr.EndoIndy said:

SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.

There is a second half to this that has not been said yet. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.

Ask again with the specifics and you will get a better answer than this one.

The figures, for anyone assembling their own picture. Worth knowing that the injection site changes very little. Abdomen, thigh and upper arm are bioequivalent for semaglutide, so a site change is not a plausible explanation for a bad week.

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part.