GLP-1s in Perimenopause — What You Need to Know First
Day 15 of the 30-day Perimenopause Series.
The Question I Get Almost Every Week
Should I just get on one of the shots? It usually arrives near the end of a visit, half-joking, and underneath it is a woman who has done everything yesterday's post described — lifted, slept, eaten the protein — and is watching the weight settle around her middle anyway. Her sister is on one. Two women at work are on one. There is an ad on her phone offering a prescription after a four-question form.
So let me answer it honestly, including the part where my answer is more cautious than the internet's.
GLP-1s are not cheating. They are not a shortcut. For the right woman at the right time, they are a tool. Just make sure you keep the muscle.
What They Actually Do
GLP-1 receptor agonists — semaglutide, tirzepatide and their relatives — mimic a gut hormone your body already makes after eating. They chemically suppress appetite in the brain and delay stomach emptying. Women describe the effect as food noise going quiet: the constant low-grade negotiation about eating simply stops. That is a real and powerful thing, and for some women it is the first relief they have had in years.
They are approved for type 2 diabetes and for chronic, long-term weight management, and the weight effect is substantial — often one to two-plus pounds a week, totaling fifteen to twenty percent of body weight. There is also solid evidence of cardiovascular benefit in specific higher-risk groups: in a large trial of adults with overweight or obesity and established cardiovascular disease but not diabetes, semaglutide reduced major cardiac events by about twenty percent. That is a serious finding and it belongs in any honest accounting of this class.
Note the phrase chronic, long-term. It is in the indication itself, and most women are never told what it means for them.
Where They Genuinely Help
There are women for whom these medications are entirely appropriate, and I do not want the caution in this post to talk them out of care they need.
Type 2 diabetes, where this class is now a mainstay of treatment.
Documented obesity meeting established criteria, particularly alongside a weight-related condition — prediabetes, hypertension, fatty liver, sleep apnea, or significant cardiometabolic risk.
Significant insulin resistance that has not responded to a genuine, supported, structured effort — not a half-hearted three weeks, but a real attempt with real support.
Women whose cardiometabolic risk is high enough that the calculus clearly favors treating it now.
For those women, withholding a medication that works because of a cultural squeamishness about weight drugs would be poor care. That is not what this post is arguing.
What I Am Arguing: They Are Prescribed Too Widely
My concern is not the drug. It is the prescribing.
A medication developed for metabolic disease is now dispensed through app-based services after a brief online questionnaire — frequently with no metabolic workup, no assessment of muscle mass or nutrition, no strength training plan, no discussion of what happens when you stop, and no follow-up that would catch a problem. Women fifteen pounds above where they would like to be are being started on a chronic injectable. Compounded versions of uncertain provenance are sold at scale.
That is not treatment. That is a transaction. And midlife women — exhausted, watching their bodies change, told for decades that thinner is the goal — are precisely the population most likely to be sold something they were never properly evaluated for.
The Muscle Problem — and Why It Matters More at 47
This is the part I most want women in this window to understand, and it is the part the advertising never mentions.
In the body-composition substudy of the STEP 1 trial, participants taking semaglutide lost about fifteen percent of their body weight over sixty-eight weeks. Fat mass fell by roughly nineteen percent and lean body mass by roughly ten percent — which works out to somewhere near forty percent of the total weight lost coming from lean tissue rather than fat.
Gradual weight loss tends to follow what is known as the quarter fat-free mass rule — about twenty-five percent of what you lose is lean tissue. So the forty percent figure is meaningfully more than you would anticipate from a slower, food-and-training approach. And with resistance training and adequate protein, lean-mass loss can be reduced to close to nothing. Same pounds on the scale. Different body at the end of it.
The Fair Counterargument
You will see that forty percent figure used online as though it means forty percent of the weight lost was muscle. It does not, and I want to be accurate with you even where accuracy softens my own point.
Lean body mass on a DXA scan is not the same as skeletal muscle. It includes water, organs, and connective tissue. In women, only around forty percent of fat-free mass is actually skeletal muscle — so the muscle loss itself is a fraction of that forty percent, not the whole of it.
Losing some lean tissue is a normal physiological response to losing weight by any method. A smaller body needs less structural tissue to carry around. This is not unique to these medications.
And in that same STEP 1 substudy, overall body composition improved. Because fat was lost preferentially, lean tissue made up a larger share of the body at the end than at the start. By that measure these participants were, proportionally, leaner.
So why do I still raise it? Because none of those caveats change what you should do about it, and because of who is in front of me. A thirty-year-old absorbs a period of lean-mass loss and rebuilds. A perimenopausal woman is already losing muscle to age and to falling estrogen, and already losing bone density fastest in exactly these years. She has less margin, and the same percentage costs her more.
Lean tissue is also not decorative. Losing it lowers your resting metabolic rate, so the medication that made you smaller can leave you burning less at rest than when you started — precisely the trap you were trying to escape. And the injection does nothing to build cardiorespiratory fitness, muscular strength, or bone density. It was never designed to. The scale rewards her for this. Her physiology does not.
What Muscle Does That a Shot Cannot
This is the mechanistic piece worth understanding even if you do end up on a medication.
A working muscle pulls sugar straight out of your blood without needing insulin at all — contraction opens its own glucose transport pathways. Nothing in a syringe replicates that. The medication route is hormone-dependent; it enhances insulin signaling rather than bypassing the need for it.
A single session of exercise improves your cells' sensitivity to insulin for roughly the next twenty-four to forty-eight hours — directly and immediately. On medication, sensitivity improves too, but indirectly and more slowly, as a downstream consequence of losing fat.
The two approaches ask different things of your pancreas. Reducing dietary sugar lowers the insulin demand you place on it. The medication prompts beta cells to secrete insulin in response to what you eat — glucose-dependently, so it does not drive insulin when your sugar is normal. Both can lower an A1C; they are not doing the same thing to get there.
Muscle is metabolically active tissue you keep. It supports your resting metabolic rate rather than eroding it, and strength training is the only item on this list that also builds the bone you are losing right now.
None of that makes the medication wrong. It makes it incomplete on its own — which is exactly why it should never be handed over without the rest of the plan attached.
What Happens When You Stop — and Most Women Do
In the STEP 1 trial extension, participants who came off semaglutide regained roughly two-thirds of the weight they had lost within about a year, and much of their metabolic improvement reversed with it. That is not a moral failure. It is what happens when you withdraw a treatment for a chronic condition.
And stopping is not the exception. Real-world persistence analyses have shown roughly half of patients discontinuing within the first year and up to about seventy percent by the second, driven mostly by cost and side effects — though those figures have been improving as supply and insurance coverage stabilize. At retail prices commonly running nine hundred to thirteen hundred dollars or more per month out of pocket, the pattern is not surprising.
Put those two facts side by side and you get the scenario I actually worry about. A woman loses forty pounds, a meaningful share of it lean tissue. She stops — because of cost, or nausea, or a job change — and regains most of the weight as fat. She now weighs what she did at the start with less muscle and a lower metabolic rate than before she began. The honest question is therefore not will this work. It is: am I prepared for this to be indefinite, can I afford it indefinitely, and if I stop, what is the plan? Ask that before the first injection, not after the twelfth.
If You and Your Clinician Decide It Is Right
Then do it properly, with the scaffolding that makes it work. Done well, this can be a genuinely good decision.
Resistance training is not optional on these medications. It is the single variable that most determines whether you lose fat or lose your body. Two to three sessions a week, started before or alongside the medication — not someday.
Protein becomes a daily discipline precisely when you least feel like eating. Appetite suppression makes under-eating protein extremely easy, and under-eating protein is how you lose the muscle. Plan it deliberately rather than waiting for hunger to remind you.
Insist on real monitoring — metabolic labs, nutritional status, and an honest conversation about bone health in a woman already in the fastest bone-loss window of her life.
Expect the common side effects rather than being blindsided: nausea, vomiting, diarrhea, constipation, and reflux are frequent, not rare.
Know the serious risks and the hard stops. There is a boxed warning for thyroid C-cell tumors — based on rodent data — which makes a personal or family history of medullary thyroid carcinoma or MEN2 a contraindication. Pancreatitis, gallbladder disease and gallstones, and severe gastroparesis are recognized risks. Not for use in pregnancy or while trying to conceive.
Get it from a clinician who examines you and follows you — not from an app, and not compounded from a source nobody can vouch for.
A Psychiatric Caution Worth Naming
This is my lane, so I will say it directly. If you have a history of an eating disorder — anorexia, bulimia, binge eating, or a long private history of restriction that never got a name — a medication whose mechanism is appetite suppression deserves serious thought and honest disclosure to whoever prescribes it. For some women it quiets a genuinely tormenting relationship with food. For others it hands a restrictive illness a powerful new tool and calls it treatment. Which of those it becomes is not something an online form can determine.
And separately: if your mood darkens after starting any medication, report it promptly rather than waiting it out.
A Note to Your People
If a woman you love is considering one of these: do not tell her it is cheating, and do not tell her she does not need it. Neither is your call. What is useful is asking whether she has been properly evaluated, whether anyone has talked to her about muscle, and whether she has a plan for what happens if she stops.
Whole-Person Steps
Before anything else, get the workup: hemoglobin A1c or fasting glucose and insulin, lipids, thyroid, liver enzymes, and vitamin D. Find out what your metabolism is actually doing.
Ask the four questions any honest prescriber should welcome: Do I meet the actual criteria? What is the plan to protect my muscle and bone? How long am I expected to stay on this? What happens if I stop or cannot afford it?
If you are not on one: give strength training and adequate protein a real six months with real support before concluding they failed you. Most women have never actually tried this version.
If you are on one: lift, eat the protein, and ask for monitoring. You can do this well — the medication and the muscle work are not in competition.
Disclose any eating disorder history to your prescriber, even if it was thirty years ago and even if it was never formally diagnosed.
Do not buy these medications from anyone who did not examine you.
If You Are in Utah
At Integrative Mind Body Psychiatry, I help women think this decision through with the whole picture in front of them — metabolic health, mood, sleep, hormones, eating history, and what they actually want their body to be able to do at seventy. I will not talk you out of a medication you need, and I will not pretend a shot is a substitute for muscle. Telehealth for adults, adolescents, and women in hormonal transitions across Utah. Insurance accepted through Headway. Learn more at integrativemindbodypsychiatry.com.
For educational purposes only. Not a substitute for individualized medical advice, and not a recommendation for or against any medication for any individual — that decision belongs to you and the clinician who examines you. Body-composition and weight-regain figures derive from the STEP 1 trial and its extension; discontinuation figures from real-world persistence analyses, which have been improving as supply and coverage stabilize.
Tomorrow: Day 16 — Bone Loss Starts in Perimenopause, Not After Menopause.
Respectfully, and with real care,
Beth Makar, RN, Dual-MSN, PMHNP-BC
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