[2026 update] Cardiovascular risk: reading the outcome trials as a set posts 91–104

Interactions between comorbidities: diabetes and kidney disease together change the risk calculation for hypoglycemia and for medication clearance. They are not independent variables.

Picking up post #89: that is the part I would want checked first.

Multiple comorbidities: a person with diabetes, kidney disease, and cardiovascular disease is outside the studied populations in most trials. Extrapolating to that person requires reasoning from the individual component trials and mechanisms.

Bariatric surgery history: altered anatomy after surgery affects absorption. That matters for oral medications and for reconstituted solutions. Discussing specific medications and doses with a clinician familiar with bariatric surgery is prudent.

Cardiovascular disease: several compounds have cardiovascular outcome trials. SELECT was in people without diabetes; SUSTAIN 6 was in high-risk diabetes. Absolute benefit is largest in high-risk people.

Obstructive sleep apnoea: SURMOUNT-OSA used an objective endpoint, the apnoea-hypopnoea index. Reduction was substantial. Whether the benefit is weight loss or a direct drug effect is not resolved by the trial.

Worth separating two things that post #93 runs together.

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

Hepatic steatosis and MASH: a phase 2 trial in semaglutide for steatohepatitis showed resolution was more frequent on treatment. Histological resolution is a surrogate for long-term clinical outcomes like cirrhosis.

Coming back to post #97, because the follow-up matters more than the original answer.

Comorbidity control: if a comorbidity (high blood pressure, high lipids) is not adequately controlled, the decision about adding compounds in this class depends on the current control status, not on the compound alone.

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

PCOS and metabolic overlap: polycystic ovary syndrome has metabolic overlap with obesity and insulin resistance. Data on compounds in this class in PCOS specifically is thin; most discussion is by mechanism.

post #101 answers the question as asked. The question underneath it is different.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

Chronic kidney disease: compounds in this class have renal benefit in people with kidney disease. The benefit appears to be additive to other renal-protective agents, not a replacement for them.

Type 2 diabetes: the population with the largest evidence base for these compounds. The SURPASS and SUSTAIN programmes established glycaemic benefit. The renal and cardiovascular benefit evidence is separate from the glycaemic benefit evidence.