This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
post #30 answers the question as asked. The question underneath it is different.
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.
Coming back to post #32, 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.
post #34 is right about the mechanism and I think understates the practical bit.
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.
Interactions between comorbidities: diabetes and kidney disease together change the risk calculation for hypoglycemia and for medication clearance. They are not independent variables.
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.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
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.
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.
Coming back to post #41, because the follow-up matters more than the original answer.
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.
Picking up post #41: that is the part I would want checked first.
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.
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.
This follows post #45 rather than contradicting it.
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.
On post #45 — agreed on the reasoning, with one qualification.
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.
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.
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.
Interactions between comorbidities: diabetes and kidney disease together change the risk calculation for hypoglycemia and for medication clearance. They are not independent variables.
On post #50 — agreed on the reasoning, with one qualification.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
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.
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.
post #56 is right about the mechanism and I think understates the practical bit.
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.
Worth separating two things that post #54 runs together.
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.
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 #58, because the follow-up matters more than the original answer.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
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