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ForumsRetatrutide & Triple AgonistsRetatrutide and blood pressure — multi-receptor cardiovascular effects

Retatrutide and blood pressure — multi-receptor cardiovascular effects

Dr.RaviCardio Sun, May 31, 2026 at 6:10 PM 10 replies 363 viewsPage 1 of 2
Dr.RaviCardio
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May 31, 2026 at 6:10 PM#1

This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes. The effect appeared earlier than the weight-loss curve can comfortably explain, which is the basis for arguing that some of the benefit is direct — anti-inflammatory and vascular — rather than purely a consequence of weight.

Where I think it is weakest: the completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.

What would genuinely help is knowing how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. If the honest answer is that nobody knows, that is a useful answer and I would rather have it.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
17 20pete_manc_UK, anna.melb_AU, mark_tokyo and 14 others
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pete_manc_UK
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May 31, 2026 at 7:53 PM#2
Dr.RaviCardio said:
SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

Fair, but phase 2 tolerability figures rarely survive contact with phase 3 scale. Triple agonism means three receptor systems generating adverse events, and the dropout column is the one I would read first when the larger trials report.

18 21RunnerRach, TrialNerd_Beth, HPLC_Greg and 15 others
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Dr.GastroMayo
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May 31, 2026 at 9:36 PM#3
Dr.RaviCardio said:
SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

I read this differently from Dr.RaviCardio, on substance rather than tone. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

19 22COA_Karl, MikeFit_NJ, InsuranceTom and 16 others
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PharmD_Rodriguez
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May 31, 2026 at 11:19 PM#4

Short answer first, then the reasoning. The glucagon component looks paradoxical and is not. Glucagon receptor agonism raises energy expenditure and drives hepatic fatty-acid oxidation, and its hyperglycaemic tendency is offset by the GLP-1 arm's insulin secretagogue effect. Net result: intake down from GLP-1/GIP, expenditure up from glucagon, glycaemia neutral or improved. It is a balancing act, and it is why the liver-fat results are the most interesting part of the dataset.

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wendy_avl
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Jun 1, 2026 at 9:24 AM#5
pete_manc_UK said:
Fair, but phase 2 tolerability figures rarely survive contact with phase 3 scale.

This matches mine closely enough to be worth saying so out loud.

21 24RickReta_CO, PharmHunterJen, TomTeleRx and 18 others
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