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Clinical · Comorbidities · continued

[2026 update] Cardiovascular risk: reading the outcome trials as a set posts 31–60

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

CN
c.niemelTL3Regular10 May 2025#31

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 15mo
ND
n.dziedzicTL2 Moderator12 May 2025#32

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.

18 likes 15mo
OC
o.cousineauTL3Regular14 May 2025#33
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

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.

4 likes in reply to #1 14mo
NN
n.nakamuraTL2 Moderator15 May 2025#34
g.pemberton_uk, post #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. Go to post

Picking up post #31: 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.

0 likes in reply to #27 14mo
EO
e.okaforTL2 Moderator17 May 2025#35

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 14mo
NV
n.vogelTL2 Moderator19 May 2025#36

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.

25 likes 14mo
SR
s.rasmussenTL2 Moderator21 May 2025#37

I read post #35 twice before replying, because I had assumed the opposite.

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.

7 likes 14mo
LT
l.trevinoTL2 Moderator22 May 2025#38
n.nakamura, post #34: Picking up post #31: 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. Go to post

This follows post #35 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.

1 like in reply to #34 14mo
BP
bench_peakTL3Regular24 May 2025#39

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 14mo
TB
t.batistaTL2 Moderator26 May 2025 · edited#40
n.hartmann, post #22: 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

post #39 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.

33 likes in reply to #22 14mo
RE
r.erdoganTL2 Moderator27 May 2025#41

post #40 answers the question as asked. The question underneath it is different.

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.

6 likes 14mo
DH
dietitian_hollisTL3Dietitian29 May 2025#42

On post #38 — 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.

16 likes 14mo
BK
b.kowalskiTL2 Moderator31 May 2025#43
NHuddleston, post #23: 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. Go to post

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.

31 likes in reply to #23 14mo
EF
e.ferreiraTL3Regular1 Jun 2025#44

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 14mo
AV
a.vukovicTL2 Moderator3 Jun 2025#45

post #44 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.

10 likes 14mo
RA
r.aldana_pharmdTL4Pharmacist5 Jun 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.

22 likes 14mo
SM
s.mbekiTL2 Moderator6 Jun 2025 · edited#47
so.mbeki, post #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. Go to post

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 #30 14mo
NA
n.abernathyTL3Analytical chemist8 Jun 2025#48

I read post #46 twice before replying, because I had assumed the opposite.

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.

1 like 14mo
KF
k.fonsecaTL2 Moderator10 Jun 2025#49

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 14mo
KV
k.vanheckeTL2 Moderator11 Jun 2025#50
f.yildiz, post #26: 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. Go to post

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.

30 likes in reply to #26 14mo
CN
cohort_notesTL2Member13 Jun 2025#51

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 13mo
SP
s.perrinTL2 Moderator15 Jun 2025#52

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 13mo
GC
glossary_checkTL2Member16 Jun 2025#53

Worth separating two things that post #49 runs together.

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 13mo
AK
an.kirchnerTL2 Moderator18 Jun 2025#54
f.rasmussen, post #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. Go to post

post #53 is right about the mechanism and I think understates the practical bit.

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 in reply to #16 13mo
EF
erratum_fileTL3Regular19 Jun 2025#55

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 13mo
HJ
h.jansenTL2 Moderator21 Jun 2025#56

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 13mo
G
GEldridgeTL3Regular22 Jun 2025 · edited#57
e.okafor, post #35: 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

On post #53 — agreed on the reasoning, with one qualification.

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.

0 likes in reply to #35 13mo
AK
a.krastevTL2 Moderator24 Jun 2025#58
NHuddleston, post #23: 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. 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.

21 likes in reply to #23 13mo
DB
d.bramleyTL3Regular26 Jun 2025#59

I read post #57 twice before replying, because I had assumed the opposite.

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.

9 likes 13mo
AN
a.nascimentoTL2 Moderator27 Jun 2025#60

This follows post #57 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.

2 likes 13mo