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Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hnselmann A, Nilsson B, Mller JE, Hjort J, Rasmussen J

The primary efficacy endpoint was the mean change from baseline in the monthly average number of headache days of at least moderate severity during the 3-month treatment period

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Feeling hot or warm: A sensation of internal warmth, particularly in the chest and core Feeling warmer than usual in the hours after injection Running warmer at night noticeably different from pre-treatment baseline Mild sweating without exertion or elevated ambient temperature Flushing: Brief episodes of facial or chest flushing Warmth that comes in waves rather than continuously Redness that resolves within minutes to hours Feeling cold (less commonly): A smaller subset of patients report the opposite feeling colder than usual Most plausible explanation: as the acute thermogenic effect subsides in the days between injections, and as substantial fat loss removes insulating tissue, some patients experience a new cold sensitivity that wasn't present before treatment What we don't know precisely: The exact percentage of retatrutide patients who experience thermal sensations this was not a reported endpoint in TRIUMPH-4 or TRIUMPH-1 Whether the effect is more pronounced at 12mg vs 9mg (though glucagon pharmacology predicts dose-dependence) How quickly it typically resolves after each injection patient reports vary What the mechanistic evidence does support clearly: glucagon receptor activation raises metabolic rate and activates brown adipose tissue thermogenesis

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