Tirzepatide vs CagriSema vs Retatrutide: Which GLP-1 WINS?
A short solo update in which Dr. Mike Moller compares tirzepatide, CagriSema and retatrutide on weight loss results, mechanism and side effects, then covers keeping muscle on these drugs.
With Dr. Mike Moller
Key moments
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- 0:00Why the new trial mattersMoller introduces the CagriSema versus tirzepatide result and says falling just short still meant large weight loss. He previews the three drugs and what he will compare.
- 1:14Semaglutide as the baselineHe describes how GLP-1 agonists reduce hunger and slow gastric emptying. He cites almost 15% weight loss at 68 weeks on 2.4 mg of semaglutide.
- 1:43Tirzepatide adds GIPMoller says Lilly added GIP receptor activity to a GLP-1 agonist and that studies often show even better weight loss. He frames the field as a race to add a mechanism without hurting tolerability or muscle.
- 2:13CagriSema against tirzepatide resultsHe reports 23% weight loss for CagriSema versus 25 and a half percent for tirzepatide at 84 weeks. He reads this as GIP looking slightly better than amylin as the add-on.
- 3:32Retatrutide's triple mechanismHe explains that retatrutide adds glucagon to GLP-1 and GIP, which he says should raise energy expenditure. He cites 28% weight loss at 68 weeks on 12 mg in phase three.
- 4:21Retatrutide side effect concernsMoller reports around 24% discontinuation for adverse effects, with higher heart rate, anxiety, poor sleep and abnormal skin sensation in about 20%. He suggests switching to another drug if these occur.
- 5:11Why muscle loss happensHe says these drugs often cause notable muscle loss because a caloric deficit pushes the body toward breaking tissue down. He stresses keeping muscle with age.
- 6:05His muscle protection checklistHe lists optimized testosterone and thyroid, roughly 1 to 2 g of protein per kilogram, weight lifting, electrolytes, hydration and adequate micronutrients.
- 7:07Final scoreboardMoller says tirzepatide edges out the approved GLP-1 drugs, CagriSema is strong and useful for practitioners, and retatrutide looks most promising but has heart rate concerns.
What the video says
Dr. Mike Moller gives a solo update of about eight minutes on three GLP-1 based weight loss drugs: tirzepatide, CagriSema and retatrutide. He builds it around the head-to-head trial in which Novo Nordisk's CagriSema was tested against Eli Lilly's tirzepatide, and around newer retatrutide results. He also covers side effects and ways to protect muscle while taking these drugs.
He starts with semaglutide as the baseline, citing almost 15% weight loss at 68 weeks on 2.4 mg in one major trial. He explains that tirzepatide adds GIP receptor activity to a GLP-1 agonist. For CagriSema, which he describes as 2.4 mg of semaglutide plus 2.4 mg of the amylin agonist cagrilintide, he reports 23% weight loss at 84 weeks against 25 and a half percent for tirzepatide at 15 mg. He concludes that adding GIP looks slightly better than adding amylin, while still calling 23% a strong result. He notes that side effects can hurt adherence in both arms.
Retatrutide is presented as a next generation tirzepatide that adds glucagon signaling to GLP-1 and GIP. Moller says glucagon is expected to raise energy expenditure and act on fat cells. He cites a phase three result of 28% weight loss at 68 weeks on 12 mg, with about 24% discontinuing because of adverse effects. He lists higher heart rate, anxiety, trouble sleeping and abnormal skin sensation, which he says affected about one in five people. His suggestion is that someone who struggles with retatrutide could switch to tirzepatide or CagriSema.
The last third is about muscle. Moller says these drugs often come with muscle loss because of the caloric deficit, and he recommends optimized hormones (testosterone and thyroid in particular), about 1 to 2 g of protein per kilogram of body weight, resistance training, electrolytes and hydration, and attention to micronutrients. His closing scoreboard puts tirzepatide ahead of the approved options, CagriSema as a strong alternative, and retatrutide as the most promising but still in trials.
On each compound
Semaglutide1:14
Moller describes semaglutide as the foundation GLP-1 agonist that reduces hunger and slows gastric emptying. He cites almost 15% weight loss at 68 weeks on 2.4 mg in one major trial.
See how your DNA reads SemaglutideTirzepatide1:43
Moller says tirzepatide combines GLP-1 with GIP activity. In the head-to-head trial he reports 25 and a half percent weight loss at 84 weeks on 15 mg, and he calls it the leader among approved GLP-1 drugs.
See how your DNA reads TirzepatideCagriSema2:13
He describes CagriSema as 2.4 mg of semaglutide plus 2.4 mg of cagrilintide. He reports 23% weight loss at 84 weeks, just short of tirzepatide, and calls it a worthwhile option with a different mechanism.
See how your DNA reads CagriSemaCagrilintide2:13
Moller identifies cagrilintide as the amylin receptor agonist half of CagriSema. He says amylin is another signal the brain uses to register fullness.
See how your DNA reads CagrilintideRetatrutide3:32
Moller calls retatrutide a GLP-1, GIP and glucagon triple agonist still in trials. He cites 28% weight loss at 68 weeks on 12 mg, with about 24% stopping for side effects including raised heart rate, anxiety, poor sleep and abnormal skin sensation.
See how your DNA reads RetatrutideWhat this video doesn’t settle
- The video gives trial figures from memory without naming the studies, so the populations, designs and doses behind each number cannot be checked from it.
- Weight loss results from different trials and different time points (68 versus 84 weeks) are placed side by side, and the video does not establish that they are directly comparable.
- The claim that adding GIP is slightly better than adding amylin rests on one trial that Moller himself says had issues.
Questions this video answers
How does CagriSema compare to tirzepatide for weight loss?
Moller reports that in a head-to-head trial CagriSema produced 23% weight loss at 84 weeks, compared with 25 and a half percent for tirzepatide at 15 mg. He notes the trial did not show CagriSema beating tirzepatide, but calls 23% still impressive.
What is retatrutide and how is it different from tirzepatide?
Moller describes retatrutide as a triple agonist that adds glucagon receptor activity to the GLP-1 and GIP activity of tirzepatide. He says glucagon signaling should raise energy expenditure and push fat cells to burn energy, and that this is what sets it apart.
What side effects of retatrutide does Dr. Moller mention?
He cites about 24% discontinuation due to adverse effects in a phase three trial. He lists higher heart rate, anxiety, trouble sleeping and abnormal skin sensation, which he says about 20% of people had.
How does Dr. Moller suggest protecting muscle on GLP-1 drugs?
He recommends optimizing hormones such as testosterone and thyroid, eating roughly 1 to 2 g of protein per kilogram of body weight, and doing weight lifting. He also advises electrolytes, hydration and enough micronutrients to avoid deficiencies like low iron or B vitamins.
Video by Dr. Michael Moeller on YouTube, embedded as published. The summary is written by PeptidesDNA from the video; every claim in it is the speaker’s. Not affiliated with or endorsed by the creator. Not medical advice.
