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Clinical · Comorbidities · continued

Hepatic steatosis: what the MASH trial evidence supports posts 31–60

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

JM
j.moreauTL2 Moderator2 May 2025#31
n.rowntree, post #22: Picking up post #19: 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. Go to post

post #30 is right about the mechanism and I think understates the practical bit.

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.

1 like in reply to #22 15mo
KO
k.otieno_statsTL3Statistician3 May 2025#32
bench_peak, post #30: 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

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.

6 likes in reply to #30 15mo
SB
s.balogunTL2 Moderator5 May 2025#33

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.

22 likes 15mo
TP
tracked_parcelTL2Regular6 May 2025#34

I read post #32 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 15mo
RV
r.vukovicTL2 Moderator8 May 2025#35
m.ndiaye, post #29: 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

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.

0 likes in reply to #29 15mo
RM
r.mcalisterTL3Regular9 May 2025#36
c.nyberg, post #3: On the opening post — agreed on the reasoning, with one qualification. 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.

3 likes in reply to #3 15mo
RN
r.nakamuraTL2 Moderator10 May 2025#37

Picking up post #34: that is the part I would want checked first.

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.

16 likes 15mo
DT
dexa_twice_yearlyTL3Regular12 May 2025 · edited#38

Coming back to post #36, 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.

31 likes 15mo
RS
r.szaboTL2 Moderator13 May 2025#39

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 15mo
GP
g.pemberton_ukTL3Regional · UK14 May 2025#40
ak.kravchenko, post #7: Worth separating two things that post #3 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

Worth separating two things that post #36 runs together.

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 in reply to #7 14mo
SF
sterile_fileTL3Regular16 May 2025#41
r.mcalister, post #36: 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

Worth separating two things that post #37 runs together.

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 #36 14mo
KB
ka.batistaTL2 Moderator17 May 2025 · edited#42

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.

32 likes 14mo
AS
a.stephanopoulosTL318 May 2025#43
NC
n.chowdhuryTL2 Moderator19 May 2025#44

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
VT
vial_tableTL2Member21 May 2025#45
n.chowdhury, post #44: 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. 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.

1 like in reply to #44 14mo
JP
j.palaciosTL2 Moderator22 May 2025#46

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 14mo
F
FairweatherTL2Member23 May 2025#47

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

23 likes 14mo
DV
d.vestergaardTL2 Moderator25 May 2025#48
ar.petrov, post #11: Picking up post #8: that is the part I would want checked first. 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… Go to post

Picking up post #45: that is the part I would want checked first.

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.

11 likes in reply to #11 14mo
VK
v.klausenTL3Regular26 May 2025 · edited#49

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 14mo
HF
h.fonsecaTL2 Moderator27 May 2025#50

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.

17 likes 14mo
YR
y.rahimiTL2 Moderator28 May 2025#51

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 14mo
AD
appeals_deskTL3Regular30 May 2025#52
g.verhoeven, post #13: 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

I read post #50 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.

7 likes in reply to #13 14mo
RP
r.petrovTL2 Moderator31 May 2025#53
bench_peak, post #30: 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

post #52 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.

18 likes in reply to #30 14mo
P
preregisteredTL3Research methods1 Jun 2025 · edited#54

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 14mo
CH
c.haddadTL2 Moderator2 Jun 2025#55

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.

4 likes 14mo
RF
resistance_firstTL2Regular4 Jun 2025#56
t.steenkamp, post #8: post #7 is right about the mechanism and I think understates the practical bit. 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

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.

12 likes in reply to #8 14mo
NV
n.vukovicTL2 Moderator5 Jun 2025#57

post #56 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.

25 likes 14mo
PN
plateau_notesTL2Regular6 Jun 2025 · edited#58

On post #54 — 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 14mo
AN
a.nascimentoTL2 Moderator7 Jun 2025#59

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.

0 likes 14mo
DB
d.bramleyTL3Regular8 Jun 2025#60
h.castellanos, post #27: 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

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.

2 likes in reply to #27 14mo