Bo Xia

[Paul Mason MD @DrPaulMason]

The widespread misuse of Ozempic is leading us headlong into a tsunami of osteoporis and sarcopenia (muscle weakness). In this note for my patients, I detail the evidence that clearly demonstrates this is not a drug to be taken lightly. If you know anyone prescribing Ozempic, they should read this.

Ozempic - a disaster waiting to happen
Glucagon-like Peptide-1 (GLP-1) is a key hormone regulating energy balance. It's release can be heavily influenced by processing of food, such as grinding, milling, or juicing, which can increase how quickly it is absorbed.

One key mechanism of GLP-1 is to suppress secretion of the hunger hormone, ghrelin, thereby suppressing hunger. GLP-1 itself is secreted by L-cells in the lower small intestine in response to the presence of nutrients incluiding carbohydrate, protein, and fat. The location of L-cells far down the small intestine is significant, as rapidly digested processed foods may not reach this far. Consequently processed foods may not stimulate an appropriate increase in GLP-1 levels, leading to persistently high ghrelin levels and hunger. This explains why one can often continue consuming large amounts of processed foods without experiencing true satiety.

Ozempic (Semaglutide) mimics the effects of natural GLP-1 but has a longer duration of action, explaining its profound appetite-suppressing effects. However, mucking around with human physiology can often have unintended consequences.

One of the trials used for the approval of Ozempic was a a drug company-funded trial known as STEP1. It demonstrated impressive weight loss over 68 weeks of once-weekly injections, the more than 1,300 participants experiencing an average weight loss of 16.86 kg (37lbs). As always however, the devil is in the detail. DEXA body composition scanning was performed on 95 of the STEP1 subjects, and revealed first of all that less than 5% of fat lost was the more problematic visceral fat. Even more concerning, 41% of the total weight lost appeared to come from muscle and bone. You read that correctly. These subjects were on a path both to osteoporosis and sarcopenia (excessive muscle loss).

This obvious raises questions about the impact of Ozempic on bone health. A double-blinded, randomised controlled trial was subsequently conducted at two public hospitals in Denmark. This study also found impairment in bone health, weekly semaglutide injections over 52 weeks resulting in bone mass loss in the lumbar spine and hip, as well as thinning of the outer strong cortical bone of the tibia. Perhaps even more concerningly however was that levels of the bone resorption marker C-terminal telopeptide (CTX) continued to rise throughout the study. This suggests that not only is bone loss ongoing while taking semaglutide, but the rate of bone loss may even accelerate with prolonged used. I cannot emphasise this enough. The longer subjects take semaglutide, the closer to osteoporosis they likely get.

Which then raises the question of what happens when semaglutide is ceased? Does bone mass return. Unfortunately we don't know the answer to this question, because the drug company funded follow-up to the STEP1 trial, which followed subjects for 12 months after discontinuing semaglutide only reported on weight, not body composition. Still even looking only at weight, the results were not good. Participants regained on average two-thirds of the weight they had lost. Given that 59% of the initial weight loss was fat, it is plausible that the regained weight was primarily composed of fat. It is perhaps unlikely that if indeed these subjects had only regained muscle and bone, that we would not have been told about it.

Additionally, the STEP1 trial found treatment with semaglutide to be associated with significant increases in the pancreatic enzyme lipase (rising from 25 U/L to 36 U/L). This is concerning given that Roche withdrew another GLP-1 agonist, Taspoglutide, due to severe side effects, including pancreatitis. Similarly, Exenatide (Byetta), another drug in this class, carries a black box warning for both pancreatitis and kidney dysfunction.

There are of course other issues with this class of drug, however I think these alone justify severe caution be used when prescribing it. The fact is, it is very likely that the longer you are on this drug, the weaker your bones get. And with no evidence that this bone mass returns when it is stopped, we may well be facing a future tsunami of premature osteoporosis and sacropenia in coming years.

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