ALL THE LATEST NEWS ABOUT GLP-1s AND FERTILITY

ALL THE LATEST NEWS ABOUT GLP-1s AND FERTILITY TREATMENT

BRIEFING: A recent article in Medscape Medical News asked a question we asked in the VOICE months ago: “Are GLP-1s the newest fertility treatments?" We, indeed, not only asked the question, but also answered it—with a great degree of certainty—in the affirmative, not only because GLPs are so incredibly successful in achieving weight loss, but because their effectiveness has transformed weight loss into a practical treatment goal that until now had not been realistic because so many infertile couples, of course, do not have the time to delay their treatment for too long. 

GLP-1s, therefore, once again lead this section of the VOICE, followed by News from the Restaurant Scene. And, of course, our list of favorite restaurants in NYC, primarily for the benefit of the many out-of-town visitors to the CHR who this month, because of the annual Foundation for Reproductive Medicine Conference, will be present in NYC in larger numbers than usual.

This new family of wonder drugs is marching on: A new study in the New England Journal of Medicine reports that once-weekly semaglutide in individuals with obesity and knee osteoarthritis with moderate-to-severe pain, unsurprisingly, resulted in significantly greater reduction in body weight and osteoarthritis-related pain than placebo. 1 An accompanying editorial, however, made additional important points: 2 First, the author notes that obesity increased the risk of knee osteoarthritis in two ways: Through obvious mechanical stress from the excessive weight on the joints, but also through the excessive visceral adipose tissue which secretes adipocytokines and other soluble mediators of pain. In addition, inflammation in the joints also contributes to pain and so do structural deteriorations through cartilage loss.

As the editorial notes, unfortunately, anti-cytokine therapies, which have been successful in rheumatoid arthritis, have been shown to be much less successful in osteoarthritis. GLP1s obviously facilitate weight loss, but also have anti-inflammatory and immunomodulatory effects. The authors in other words suggest that the observed improvement in knee pain may not only be due to the wight loss. A

nd knee osteoarthritis is not the only new indication for GLPs: An abstract at the annual ASRM conference in Denver presented by researchers from Harvard University claimed that GLP-1s offer in women with type 2 diabetes better protective benefits from developing uterine fibroids than metformin and insulin. This has relevance because, as the investigators noted, type 2 diabetes and obesity are associated with insulin resistance which, in turn, is associated with increased risk of developing fibroid tumors. 3 Does this mean that GLP-1s may be able to decrease the prevalence of fibroids in genetically predisposed women even if they are not obese and diabetic?

And not to be forgotten, in patients with type 2 diabetes semaglutide was also shown to be associated with a 40% to 70% reduction in risk for first-time Alzheimer’s disease, in comparison to other diabetes medications. 4 But not everything that shines is gold: One increasing concern – though so-far available data are still contradictory – is the possible association of significant weight loss from GLP-1s (especially in older individuals) with sarcopenia 5 which – as the article notes – creates a two-fold increased risk of mortality. 

Also based on an abstract at ASRM 2024 in Denver an anonymous article in Healio quotes Richard S. Legro, MD, chair of OB/GYN at Penn State Health in Hershey, PA, as reemphasizing that, due to GLP-1s, the subject of wight loss for obese patients with infertility is coming up in counseling more often than before, “but comes with its own list of risks and benefits that must be carefully considered.” 6

The two key takeaways of the article were that (i) women with obesity can (still) successfully become pregnant, often without fertility treatments; and (ii) clinicians should avoid perpetuating stigma when discussing weight loss with patients struggling to conceive.

We are not sure we would word the conclusions in this way because Lego himself very well describes how quintessential an issue obesity has become in regard to infertility in women as well as men: Ca. 40% of all infertility patients are obese. Moreover, obesity is associated with basically every adverse fertility outcome, from time to pregnancy, to pregnancy loss, pregnancy complications, preterm delivery, gestational diabetes, preeclampsia, Cesarean section rates large for gestational age infants, and neonatal adverse outcomes.

While noting all of these associations, he in the next sentence is quoted as saying that the effects of obesity are “exaggerated in the public’s and clinicians’ minds.” Sounds to us a little contradictory!

Finally, a Feature article by life science reporter Mariana Lenharo in Nature magazine asked the quintessential question, why do obesity drugs seem to treat so many other ailments? The final answer is, of course, not known yet, but it is already obviously clear that it is more than just weight loss that offers so many different clinical benefits. One of those, as the article notes, is the taming of inflammation. Another is – because of the ability to cross into the brain – substantial central-nervous system effects from anti-addictive behavior, to Parkinson’s and Alzheimer’s (see above), and according to most recent reports maybe also in depression.

REFERENCES

1. Bliddal et al., N Engl J Med 2024’391:171573-1583

2. Felson DT.N Engl J Med 2024;391:17:1643-1644

3. Jin Hsieh et al., Fertil Steril 2024. DOI: 10.1016/j.fertnstert.2024.07.360

4. Wang et al., Alzheimer’s Dement 2024:;1-12. DOI: 101002/alz.14313

5. Lucas EJ. Medscape Diabetes & Endocrinology. October 16, 2024. https://www.medscape.com/viewarticle/unseen-cost-weight-loss-and-aging-tackling-sarcopenia-2024a1000inn?form=fpf

6. Healio.October 21, 2024. https://www.healio.com/news/womens-health-ob-gyn/20241021/patients-need-honest-data-why-weight-loss-is-not-an-easy-answer-for-infertility