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Clinical · Comorbidities

[2026 update] Cardiovascular risk: reading the outcome trials as a set

SO
sa.okonkwoTL2 Moderator2 Mar 2025#1

Posting this under the heading it deserves: Cardiovascular risk: reading the outcome trials as a set Everything below is what sits behind that.

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 to understand what the honest position is when someone falls outside the studied population: not "it is fine" and not "there is no data", but what the reasoning actually looks like.

2 likes 17mo
AW
a.weissTL2 Moderator7 Mar 2025#2

On the opening post — agreed on the reasoning, with one qualification.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

5 likes 17mo
KR
k.roosTL2 Moderator10 Mar 2025#3

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.

21 likes 17mo
LD
l.dziedzicTL2 Moderator13 Mar 2025#4

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
NL
n.lehtinenTL2 Moderator16 Mar 2025#5
l.dziedzic, post #4: 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. Go to post

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.

0 likes in reply to #4 16mo
IB
i.bakkenTL2 Moderator19 Mar 2025#6
n.lehtinen, post #5: 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. Go to post

Worth separating two things that post #2 runs together.

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.

3 likes in reply to #5 16mo
K
KLindqvistTL4 Moderator22 Mar 2025 · edited#7
Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.

This follows post #4 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.

15 likes 16mo
KL
k.laurentTL2 Moderator24 Mar 2025#8

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.

29 likes 16mo
SK
s.karlsen_rphTL3Pharmacist27 Mar 2025#9
sa.okonkwo, post #1: Posting this under the heading it deserves: Cardiovascular risk: reading the outcome trials as a set Everything below is what sits behind that. 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… Go to post

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.

5 likes in reply to #1 16mo
HV
h.vargaTL2 Moderator29 Mar 2025#10

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

14 likes 16mo
NG
np_gilmoreTL3Nurse practitioner31 Mar 2025#11

Coming back to post #9, because the follow-up matters more than the original answer.

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.

8 likes 16mo
NS
no.silvaTL2 Moderator3 Apr 2025 · edited#12

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.

2 likes 16mo
PP
peak_purityTL35 Apr 2025#13
SD
s.dialloTL2 Moderator7 Apr 2025#14

post #13 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.

27 likes 16mo
PR
policy_readerTL2Regular9 Apr 2025#15

I read post #13 twice before replying, because I had assumed the opposite.

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
FR
f.rasmussenTL2 Moderator11 Apr 2025#16

This follows post #13 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.

0 likes 16mo
MD
m.dalgaardTL3Regular13 Apr 2025#17
h.varga, post #10: 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

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 #10 15mo
MV
m.vukovicTL2 Moderator15 Apr 2025#18
KLindqvist, post #7: This follows post #4 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

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 #7 15mo
RH
revision_historyTL3Wiki editor17 Apr 2025 · edited#19

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.

2 likes 15mo
EM
e.mbekiTL2 Moderator19 Apr 2025#20

Picking up post #17: that is the part I would want checked first.

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.

0 likes 15mo
ST
stopper_traceTL2Member21 Apr 2025#21

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.

5 likes 15mo
NH
n.hartmannTL2 Moderator23 Apr 2025#22
i.bakken, post #6: Worth separating two things that post #2 runs together. 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

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

14 likes in reply to #6 15mo
N
NHuddlestonTL1Member25 Apr 2025 · edited#23
s.diallo, post #14: post #13 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. Go to post

post #22 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.

0 likes in reply to #14 15mo
MG
m.guerreroTL2 Moderator27 Apr 2025#24

On post #20 — 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 15mo
W
WendelboeTL2Member29 Apr 2025#25

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.

2 likes 15mo
FY
f.yildizTL2 Moderator1 May 2025#26
n.lehtinen, post #5: 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. 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.

9 likes in reply to #5 15mo
GP
g.pemberton_ukTL3Regional · UK3 May 2025#27

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.

28 likes 15mo
AV
ai.vukovicTL2 Moderator5 May 2025#28

Worth separating two things that post #24 runs together.

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

0 likes 15mo
OT
osmolal_tableTL1Member6 May 2025#29

Picking up post #26: that is the part I would want checked first.

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.

13 likes 15mo
SM
so.mbekiTL2 Moderator8 May 2025#30

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.

27 likes 15mo