Semaglutide for weight loss?

Semaglutide is the new kid on the weight-loss block, but it’s looking promising (with some caveats!).

Most popularly by brand names Ozempic and Wegovy, it was first trialled to help diabetics*, and is now sought-after by the rest of the population too. So far, only Wegovy is FDA-approved for weight loss. It contains more semaglutide than Ozempic, and was developed specifically for weight loss, rather than for diabetes.

*Specifically: diabetics with type 2 diabetes. Because it works by helping the pancreas to make insulin, it’s of no help whatsoever to T1D folks, sadly. If you’re T1D and reading this though, today’s book of the day is for you!

First things first: does it work as marketed for diabetes?

It does! At a cost: a very common side effect is gastrointestinal problems—same as for tirzepatide, which (like semaglutide) is a GLP-1 agonist, meaning it works the same way. Here’s how they measure up:

• Head-to-head study: Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes
• Head-to-head systematic review: Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes

As you can see, both of them work wonders for pancreatic function and insulin sensitivity!

And, both of them were quite unpleasant for around 20% of participants:

❝Tirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. Gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups.❞

~ Zaazouee et al., 2022

What about for weight loss, if not diabetic?

It works just the same! With just the same likelihood of gastro-intestinal unpleasantries, though. There’s a very good study that was done with 1,961 overweight adults; here it is:

Once-Weekly Semaglutide in Adults with Overweight or Obesity

The most interesting things here are the positive results and the side effects:

❝The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% confidence interval [CI], −13.4 to −11.5; P<0.001).❞

~ Wilding et al., 2021

In other words: if you take this, you’re almost certainly going to get something like 6x better weight loss results than doing the same thing without it.

❝Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%])❞

~ ibid.

In other words: you have about a 3% chance of having unpleasant enough side effects that you don’t want to continue treatment (contrast this with the 20%ish chance of unpleasant side effects of any extent)!

Any other downsides we should know about?

If you stop taking it, weight regain is likely. For example, a participant in one of the above-mentioned studies who lost 22% of her body weight with the drug’s help, says:

❝Now that I am no longer taking the drug, unfortunately, my weight is returning to what it used to be. It felt effortless losing weight while on the trial, but now it has gone back to feeling like a constant battle with food. I hope that, if the drug can be approved for people like me, my [doctor] will be able to prescribe the drug for me in the future.❞

~ Jan, a trial participant at UCLH

Source: Gamechanger drug for treating obesity cuts body weight by 20% <- University College London Hospitals (NHS)

Is it injection-only, or is there an oral option?

An oral option exists, but (so far) is on the market only in the form of Rybelsus, another (slightly older) drug containing semaglutide, and it’s (so far) only FDA-approved for diabetes, not for weight loss. See:

A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes ← for the science

FDA approves first oral GLP-1 treatment for type 2 diabetes ← For the FDA statement

Where can I get these?

Availability and prescribing regulations vary by country (because the FDA’s authority stops at the US borders), but here is the website for each of them if you’d like to learn more / consider if they might help you:

Rybelsus / Ozempic / Wegovy

First, a quick disambiguation:

• chromium found in food, trivalent chromium of various kinds, is safe (in the quantities usually consumed) and is sometimes considered an essential mineral, sometimes considered unnecessary but beneficial. It’s hard to know for sure, since it’s in a lot of foods (naturally, like many trace elements)
• chromium found in pollution, hexavalent chromium (so: twice as many cationic bonds, if this writer’s chemistry serves her correctly) is poisonous.

We’re going to be writing about the food kind, which is also possible to take as a supplement.

In this case, supplementing vs getting from food is quite a big difference, by the way, since (unlike for a lot of things, which are often the other way around) the bioavailability of chromium from food is very low (around 2.5%), whereas chromium picolinate, one of the most commonly-used supplement forms, boasts higher bioavailability.

Does it work for blood sugars?

Yes, it does! At least, it does in the case of people with type 2 diabetes. Rather than bombard you with many individual studies, here’s a systematic review and meta-analysis of 22 criteria-meeting randomized clinical trials that found:

❝The available evidence suggests favourable effects of chromium supplementation on glycaemic control in patients with diabetes.

Chromium monosupplement may additionally improve triglycerides and HDL-C levels.❞

Source: Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes

Type 1 diabetes does not have anything like the same weight of evidence, and indeed, we couldn’t find a single human study. It was beneficial for mice with artificially-induced T1D, though wait no, we have an update! We found literally a single human study:

Chromium picolinate supplementation for diabetes mellitus

Literally, as in: it’s a case study of one person, and the results were a modest reduction in Hb A1c levels after 3 months of 600μg daily; the researchers concluded that ❝chromium picolinate continues to fall squarely within the scope of “alternative medicine,” with both unproven benefits and unknown risks❞.

As for people without diabetes, it may reduce the risk of diabetes:

Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements

However! This was an observational study, and correlation ≠ causation.

Furthermore, they said:

❝Over one-half the adult US population consumes nutritional supplements, and over one-quarter consumes supplemental chromium. The odds of having T2D were lower in those who, in the previous 30 d, had consumed supplements containing chromium❞

That “over one-quarter consumes supplemental chromium” brought our attention to the fact that this is not talking about specifically chromium “monosupplements” (definitely not quarter of the adult population take those), but rather, “multivitamin and mineral” supplements that also contain a tiny amount (often under 50μg) of chromium.

In other words, this ruins the data and honestly the benefit could have been from anything in the “multivitamin and mineral” supplement, or indeed, could just be “the kind of person who takes supplements is the kind of person who lives a lifestyle that is less conducive to becoming diabetic”.

Does it work for weight loss?

We’re running out of space here, so we’ll be brief:

No.

There are many papers that have concluded this, but here are two:

Chromium picolinate supplementation for overweight or obese adults

and

The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent

Is it safe?

Science’s current best answer is “we don’t know; it hasn’t been tested enough; we haven’t even established the tolerable upper limit, which is usually step 1 of establishing safety”.

Nor is there an estimated average requirement (if indeed there even is a requirement, which question is also not as yet answered conclusively by science), and science falls back to “here’s an average of what people consume in their diet, so that’s probably safe, we guess”.

(that average was reckoned as 25μg/day for young women and 25μg/day for young men, by the way; older ages not as yet reckoned)

You can read about this sorry state of affairs here.

Want to try some?

Notwithstanding the above lack of data for safety, it does have benefits for blood sugars, so if that’s a gamble you’re willing to make, then here’s an example product on Amazon.

Note: the dosage per capsule there (800μg) is half of the low end of the dose that was implicated in the serious kidney condition caused in this case study (1200–2400μg), so if you are going to try it, we strongly recommend not taking more than one per day.

Take care!