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Clinical · Comorbidities · continued

Obstructive sleep apnoea and a hard endpoint in this class posts 31–60

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.

TS
taper_shiftTL3Regular11 Mar 2025#31

I read post #29 twice before replying, because I had assumed the opposite.

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.

0 likes 17mo
JC
j.cabreraTL2 Moderator12 Mar 2025 · edited#32
h.falk, post #19: Worth separating two things that post #15 runs together. 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. Go to post

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.

29 likes in reply to #19 17mo
F
FFaulknerTL3Regular14 Mar 2025#33

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.

14 likes 16mo
VO
v.okonkwoTL2 Moderator15 Mar 2025#34

post #33 is right about the mechanism and I think understates the practical bit.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

5 likes 16mo
T
ThibodeauTL3Regular16 Mar 2025#35

Coming back to post #33, 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.

0 likes 16mo
FC
f.chowdhuryTL2 Moderator18 Mar 2025#36

Picking up post #33: that is the part I would want checked first.

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.

0 likes 16mo
CI
c.inglethorpeTL319 Mar 2025#37
RM
r.molnarTL2 Moderator20 Mar 2025#38

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.

9 likes 16mo
LP
l.piresTL2 Moderator22 Mar 2025 · edited#39
da.bakker, post #11: Interactions between comorbidities: diabetes and kidney disease together change the risk calculation for hypoglycemia and for medication clearance. They are not independent variables. Go to post

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.

30 likes in reply to #11 16mo
ME
m.ekstromTL2 Moderator23 Mar 2025#40
t.wojcik, post #3: post #2 is right about the mechanism and I think understates the practical bit. 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. Go to post

This follows post #37 rather than contradicting it.

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.

15 likes in reply to #3 16mo
JD
j.delacroixTL3Regular24 Mar 2025#41

Picking up post #38: that is the part I would want checked first.

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.

0 likes 16mo
CF
c.falkTL2 Moderator26 Mar 2025#42

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.

5 likes 16mo
CW
cohort_watchTL2Member27 Mar 2025#43
l.pires, post #39: 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. Go to post

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.

20 likes in reply to #39 16mo
RM
ra.mensaTL2 Moderator28 Mar 2025#44
hana.sato, post #7: post #6 answers the question as asked. The question underneath it is different. 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. Go to post

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.

0 likes in reply to #7 16mo
ML
m.lindqvistTL2 Moderator29 Mar 2025#45

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.

0 likes 16mo
RR
r.restrepoTL2 Moderator31 Mar 2025#46

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

2 likes 16mo
AW
a.westergaardTL3Regular1 Apr 2025#47

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.

14 likes 16mo
DY
d.yilmazTL22 Apr 2025#48
ML
m.lehtinenTL2 Moderator3 Apr 2025#49

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.

0 likes 16mo
CC
c.cardosoTL2 Moderator5 Apr 2025#50

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.

0 likes 16mo
TD
t.dumitruTL2 Moderator6 Apr 2025#51

On post #47 — 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.

0 likes 16mo
C
chromatogramTL4Analytical chemist7 Apr 2025 · edited#52
owen.brady, post #1: On the subject in the title: Obstructive sleep apnoea and a hard endpoint in this class Working notes rather than a conclusion. Asking about a population rather than about a person. The published trials in this class mostly enrolled a fairly specific group, and the questions here frequently come from people well outside it. I would like… Go to post

post #51 answers the question as asked. The question underneath it is different.

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.

26 likes in reply to #1 16mo
RE
r.ekstromTL2 Moderator8 Apr 2025#53
f.chowdhury, post #36: Picking up post #33: that is the part I would want checked first. 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. Go to post

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.

8 likes in reply to #36 16mo
EF
endo_fellow_rkTL3Endocrinology fellow9 Apr 2025#54

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.

2 likes 16mo
MB
m.brobergTL2 Moderator11 Apr 2025#55

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.

0 likes 16mo
CB
c.bakkerTL2 Moderator12 Apr 2025#56
t.dumitru, post #51: On post #47 — 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. Go to post

post #55 is right about the mechanism and I think understates the practical bit.

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.

0 likes in reply to #51 16mo
AW
a.wikstromTL2 Moderator13 Apr 2025#57

I read post #55 twice before replying, because I had assumed the opposite.

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.

12 likes 15mo
SL
s.leclercTL4 Moderator14 Apr 2025#58
Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.

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.

4 likes 15mo
LV
l.vukovicTL2 Moderator15 Apr 2025 · edited#59
b.jansen, post #27: This follows post #24 rather than contradicting it. 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. Go to post

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

27 likes in reply to #27 15mo
WP
weekly_pinTL2Regular17 Apr 2025#60
c.wijnberg, post #14: This follows post #11 rather than contradicting it. 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. Go to post

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.

13 likes in reply to #14 15mo