Microdosing GLP-1 and Cagrisema headlines
Two clinicians on the Docs Who Lift podcast argue against microdosing GLP-1 drugs, mainly from compounded supplies, and go through the topline CagriSema REDEFINE 1 results.
With Dr. Spencer Nadolsky, Dr. Carl
Key moments
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- 0:31Topline CagriSema results and expectationsThe hosts introduce the day's topics and say the CagriSema headline came in around 22%, short of the 25% target they say Novo Nordisk wanted. They still call that result good by earlier standards.
- 2:10What microdosing meansNadolsky says microdosing was popularized by a naturopathic doctor and that low and slow titration is old, but sub-therapeutic dosing is newer. He frames it against how dosing trials normally work.
- 6:13Semaglutide phase 2 dosing dataNadolsky cites a 2016 Diabetes Care phase 2 trial. He says the 0.1 mg dose matched or trailed placebo on A1C and weight, and benefit appeared at 0.2 mg and above.
- 9:18A patient on a lower doseNadolsky describes a patient with type 1 diabetes who he says stayed on 0.5 mg weekly, lost almost 14% of her weight and cut her insulin from about 50 to 24 units daily. He calls this therapeutic, not true microdosing.
- 11:02Why he avoids compounded microdosesHe says compounded low doses lack long-term data, especially on cardiovascular outcomes. He would use compounded drugs only for someone who cannot get the approved product.
- 19:03Tirzepatide microdose and inflammation claimsThe hosts criticize a longevity figure taking 0.5 mg tirzepatide for inflammation. Nadolsky cites an early dosing study where that dose gave weight loss similar to placebo and slightly higher fasting glucose.
- 27:18Cagrilintide and the amylin backgroundThey explain CagriSema as semaglutide plus cagrilintide, a long-acting amylin analog. They contrast it with the older pramlintide, which needed mealtime dosing and never caught on.
- 28:58Earlier CagriSema trialsNadolsky recaps phase 2 and phase 1b results. He says the combination reached roughly 15 to 17% weight loss at 20 weeks against about 8% for semaglutide.
- 30:20REDEFINE 1 topline numbersThey give the phase 3 design and headline figures: 68 weeks, fixed dose, about 23% weight loss for those who stayed on drug, and over 40% reaching 25% or more. They also note lower top-dose completion with the combination.
- 33:23Supply, pricing and what comes nextThe hosts discuss vial pricing, possible approval in 2025 and upcoming drugs such as retatrutide. They end by repeating that low doses are fine when used as indicated and that compounded versions need caution.
What the video says
This episode of the Docs Who Lift podcast has two clinician hosts covering two news items. The first is the idea of microdosing GLP-1 drugs, which they say was popularized by a naturopathic doctor. The second is the topline release of the CagriSema phase 3 trial, REDEFINE 1. The hosts also spend time on drug pricing, compounding pharmacies and corporate behavior, which is outside the peptide content.
On microdosing, Nadolsky says the idea of going low and slow is not new, but that sub-therapeutic doses are a different matter. He walks through a published phase 2 semaglutide dosing trial, in which he says the 0.1 mg weekly dose performed about the same as placebo, and the 0.2 mg dose began to show an effect on A1C. He applies the same reasoning to tirzepatide, citing an early dosing study where a 0.5 mg dose produced weight loss about equal to placebo. He argues that a person on a very low dose would not know whether any long-term benefit exists, and he objects to the claim that tiny doses reduce inflammation. He does describe patients who feel well on lower approved doses, including a person with type 1 diabetes who he says lost almost 14% of body weight on 0.5 mg weekly. He says he would use compounded versions only when a patient truly cannot get the approved drug.
The second half covers CagriSema, a fixed-dose combination of semaglutide and cagrilintide, an amylin analog. The hosts say the 68-week trial enrolled about three and a half thousand people and compared the combination with each component and with placebo. They report weight loss near 23% among those who stayed on treatment, against about 12% for cagrilintide, 16% for semaglutide and 2.5% for placebo. They also flag that fewer people on the combination reached the top dose. They treat the result as good, though short of the 25% Novo Nordisk reportedly wanted, and they say the full data are not yet published.
On each compound
Semaglutide6:13
Nadolsky says a phase 2 trial showed 0.1 mg weekly performing like placebo and benefit beginning at 0.2 mg. He also says some patients do well on 0.5 mg, below the labeled maintenance dose.
See how your DNA reads SemaglutideTirzepatide19:03
Nadolsky says a 0.5 mg dose, far below the 2.5 mg starting dose, produced weight loss about the same as placebo in an early trial. He says fasting glucose rose slightly, while approved doses lowered it.
See how your DNA reads TirzepatideCagrilintide27:18
The hosts describe it as a long-acting amylin analog and a successor to pramlintide. They say it slows gastric emptying, supports insulin secretion, suppresses glucagon and increases satiety.
See how your DNA reads CagrilintideCagriSema30:20
The hosts report REDEFINE 1 topline results of almost 23% weight loss among those who stayed on treatment, versus 16% for semaglutide, about 12% for cagrilintide and 2.5% for placebo. They note only 57% of the combination group reached the top dose.
See how your DNA reads CagriSemaRetatrutide1:01
The hosts describe it as a GLP-1, GIP and glucagon triple agonist that they say is expected to reach 25% weight loss. They say they are waiting for phase 3 data.
See how your DNA reads RetatrutideWhat this video doesn’t settle
- The CagriSema figures are press-release topline numbers, and the hosts say the full REDEFINE 1 data had not yet been published.
- The dosing-trial comparisons are Nadolsky's own selection of short studies, so they do not show what microdosing does over months or years.
- The patient with type 1 diabetes is a single case with no control group, and the hosts call the dose therapeutic, not a true microdose.
Questions this video answers
Does microdosing semaglutide work according to Dr. Nadolsky?
Nadolsky says a phase 2 trial found the 0.1 mg weekly dose no better than placebo for A1C or weight, with benefit starting around 0.2 mg. He allows that some patients do well on lower approved doses, but says true microdoses lack supporting data.
What does Dr. Nadolsky say about compounded GLP-1 microdoses?
He says compounded low doses have not been studied long term, so claims about cardiovascular benefit cannot be made. He would consider compounded product only when a patient cannot obtain the approved drug.
What were the CagriSema REDEFINE 1 results?
The hosts say the 68-week trial showed almost 23% weight loss in people who stayed on the combination, compared with about 12% for cagrilintide, 16% for semaglutide and 2.5% for placebo. They stress that only topline figures were available.
Does a low dose of tirzepatide reduce inflammation?
Nadolsky says there is no good data for that claim. He cites an early dosing study where 0.5 mg gave weight loss about like placebo and slightly raised fasting glucose, and he says it is unknown whether such a dose offers any benefit.
Video by Dr. Spencer Nadolsky 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.
