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Clinical · Comorbidities · continued

[2026 update] Cardiovascular risk: reading the outcome trials as a set posts 61–90

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

CL
customs_ledgerTL3Regular29 Jun 2025#61

This follows post #58 rather than contradicting it.

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.

18 likes 13mo
FW
f.weissTL2 Moderator30 Jun 2025#62
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

I read post #60 twice before replying, because I had assumed the opposite.

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 in reply to #35 13mo
DS
dr_seongTL3Physician2 Jul 2025#63
h.jansen, post #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. 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.

1 like in reply to #56 13mo
CV
c.vasquezTL2 Moderator3 Jul 2025#64

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.

7 likes 13mo
CO
c.okaforTL3Regular5 Jul 2025#65

Picking up post #62: that is the part I would want checked first.

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 13mo
KA
k.asanteTL2 Moderator6 Jul 2025#66

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 13mo
WN
w.novakTL3Regular8 Jul 2025#67
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

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.

17 likes in reply to #1 13mo
NK
n.kravchenkoTL2 Moderator9 Jul 2025 · edited#68

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.

33 likes 13mo
V
VPoulsenTL3Regular11 Jul 2025#69
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

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.

8 likes in reply to #10 13mo
IW
i.wojcikTL2 Moderator12 Jul 2025#70
Wendelboe, post #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. Go to post

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.

19 likes in reply to #25 13mo
D
DKwiatkowskiTL3Regular14 Jul 2025#71

Worth separating two things that post #67 runs together.

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.

11 likes 12mo
DA
d.achebeTL2 Moderator15 Jul 2025 · edited#72

post #71 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.

3 likes 12mo
TF
taper_fileTL3Regular17 Jul 2025#73
n.abernathy, post #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. 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 #48 12mo
HK
h.krastevTL2 Moderator18 Jul 2025#74
o.cousineau, post #33: 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

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.

24 likes in reply to #33 12mo
N
NicolaidesTL3Regular20 Jul 2025#75

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.

7 likes 12mo
WV
w.verhoevenTL2 Moderator21 Jul 2025#76

post #75 answers the question as asked. The question underneath it is different.

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.

1 like 12mo
N
NorringtonTL3Regular23 Jul 2025#77
b.kowalski, post #43: 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

Coming back to post #75, because the follow-up matters more than the original answer.

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 #43 12mo
GT
g.tammTL2 Moderator24 Jul 2025#78

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.

17 likes 12mo
DM
d.magalhesTL2Member26 Jul 2025 · edited#79

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.

23 likes 12mo
AW
am.wikstromTL2 Moderator27 Jul 2025#80

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.

10 likes 12mo
EK
ew.kuuselaTL2 Moderator29 Jul 2025#81

post #80 is right about the mechanism and I think understates the practical bit.

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 12mo
TW
t.waldenstrmTL2Member30 Jul 2025#82

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

1 like 12mo
TB
t.brandtTL2 Moderator31 Jul 2025#83
s.karlsen_rph, post #9: 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

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.

7 likes in reply to #9 12mo
KB
k.bettencourtTL2Member2 Aug 2025#84

I read post #82 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.

17 likes 12mo
JS
j.solbergTL2 Moderator3 Aug 2025#85

post #84 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.

33 likes 12mo
L
LundqvistTL2Member5 Aug 2025#86

On post #82 — 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.

0 likes 12mo
FL
f.laurentTL2 Moderator6 Aug 2025#87
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 12mo
SE
septum_entryTL2Member8 Aug 2025#88

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.

12 likes 12mo
AV
a.vestergaardTL2 Moderator9 Aug 2025#89

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.

1 like 12mo
GD
glossary_deskTL3Regular10 Aug 2025#90

Worth separating two things that post #86 runs together.

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.

6 likes 12mo