GLP-1 Medications: Where They Shine, Where They Fail, and What We Still Don’t Know
GLP-1–based drugs (Ozempic, Wegovy, Mounjaro, Zepbound, etc.) have gone from quiet diabetes meds to “weight-loss shots” and now, in some cases, cardiovascular and sleep-apnea drugs.
They started as type 2 diabetes treatments, proved highly effective for weight loss, and now have strong data for cardiovascular risk reduction in high-risk patients. At the same time, large trials for Alzheimer’s disease have been negative, and we’re still sorting out questions around sexual drive, cancer, and even compulsive behaviors like alcohol or gambling.
Here’s how I explain them to patients.
Educational only, not personal medical advice. Please talk with your own clinician before starting or stopping any medication.
A brief history
GLP-1 (glucagon-like peptide-1) is a gut hormone that helps regulate insulin, glucagon, stomach emptying, and appetite. The first GLP-1 drug, exenatide, was synthesized from exendin-4, a peptide originally isolated from the saliva of the Gila monster lizard in the early 1990s and approved by the FDA in 2005.Over time, we got once-weekly versions (dulaglutide, semaglutide, etc.) and higher doses, which led to:
Strong A1c lowering
Substantial weight loss
Cardiovascular benefits in high-risk patients with diabetes
Where GLP-1s are clearly helpful
Type 2 diabetes
In type 2 diabetes, long-acting GLP-1 RAs:
Lower A1c by roughly 1–1.5 percentage points
Promote clinically meaningful weight loss
Have low hypoglycemia risk
Reduce heart attack and stroke in high-risk patients in multiple large trials
For many with diabetes plus cardiovascular or kidney disease, a GLP-1 RA is now a core cardiometabolic drug, not just a glucose medication.
Obesity and cardiovascular risk
At obesity doses (e.g., semaglutide 2.4 mg / Wegovy), average weight loss in trials is around 15% of body weight, with improvements in BP, lipids, sleep apnea severity, mobility, and quality of life.
The SELECT trial showed semaglutide 2.4 mg reduced major cardiovascular events in people with obesity and cardiovascular disease but without diabetes, leading to FDA approval for CV risk reduction in this group.
Osteoarthritis: weight + pain
In people with obesity and knee osteoarthritis, once-weekly semaglutide 2.4 mg produced:
Greater weight loss
Significantly larger reductions in knee pain
Improved function
Obstructive sleep apnea (OSA)
The SURMOUNT-OSA phase 3 trials showed that tirzepatide (Zepbound) in adults with obesity and moderate-to-severe OSA:
Reduced the apnea–hypopnea index (AHI)
Lowered body weight, hypoxic burden, hsCRP, and systolic BP
Improved sleep-related patient-reported outcomes compared with placebo
In December 2024, the FDA approved Zepbound as the first medication specifically indicated for moderate-to-severe OSA in adults with obesity, alongside diet and physical activity.
Which GLP1 is the “best”?
In head-to-head trials in people with obesity, tirzepatide has produced greater average weight loss than semaglutide—on the order of ~20% vs ~14% body-weight reduction. Both drugs share a similar side-effect pattern: nausea, vomiting, diarrhea, and constipation are the most common issues, usually mild to moderate and dose-related though it appears fewer people stop taking tirzepatide due to side effects.
Where they have not worked: Alzheimer’s disease
There was genuine hope that GLP-1s could help Alzheimer’s disease, based on animal data and early human signals.
The large phase 3 EVOKE and EVOKE+ trials of oral semaglutide in early Alzheimer’s were reported negative for cognitive outcomes: biomarkers moved in favorable directions, but there was no meaningful slowing of clinical decline versus placebo.
Right now, GLP-1s are not an Alzheimer’s treatment. Any future role will depend on earlier or different targets and still needs to be proven.
Where uncertainty remains
Sexual drive and function
Patients ask about this a lot; data are still sparse.
Large GLP-1 trials rarely measured libido or sexual satisfaction as primary endpoints.
Early reports and pharmacovigilance data suggest mixed effects: some people report improved sexual function (from weight loss, better confidence, better metabolic health), others report reduced libido or anhedonia.
A possible mechanism: GLP-1s appear to dampen dopamine-mediated reward responses, which may be helpful for cravings, but could also blunt some forms of desire, including sexual.
Cancer: mixed signal, big picture
There are three main threads:
Rodent C-cell tumors → hence the medullary thyroid carcinoma / MEN2 class warning.
Human data so far: large trials and meta-analyses have not shown a clear increase in overall cancer, thyroid cancer, or pancreatic cancer, but follow-up is still relatively short for what may become decades-long use.
A large JAMA Network Open study of more than 1.6 million people with type 2 diabetes found that GLP-1 RAs were associated with a significantly lower risk of 10 of 13 obesity-related cancers compared with insulin, but no clear advantage over metformin, and a higher risk of kidney cancer vs metformin.
Compulsive habits: alcohol, gambling, and reward circuitry
This is one of the more intriguing (and early) frontiers.
Preclinical work shows GLP-1 signaling can reduce alcohol and drug intake in animals, likely by blunting dopamine release in reward pathways.
Observational studies and early trials suggest GLP-1 RAs may reduce alcohol consumption and cravings in people with alcohol use disorder, and real-world data show lower alcohol-related events in GLP-1 users vs controls.
Addiction researchers are exploring GLP-1s for other compulsive behaviors (opioids, nicotine, gambling, compulsive shopping), with early human data and expert commentary suggesting promise but not proof.
Body composition and muscle
Finally, what you lose matters:
GLP-1-driven weight loss includes both fat and lean mass.
Without resistance training and adequate protein, you can end up lighter but also weaker and less robust.
In my practice, if someone starts a GLP-1, we almost always pair it with:
A resistance-training program plus
Attention to protein intake
I’d rather see slightly slower weight loss with better muscle preservation than maximal speed and a big hit to lean mass.
How I frame GLP-1s in a concierge setting
When someone asks, “Should I go on Ozempic / Wegovy / Mounjaro / Zepbound?” we walk through three questions:
Are you in a group where benefits are clearly high?
Type 2 diabetes with cardiovascular or kidney risk
Obesity or overweight with comorbidities, where meaningful weight loss would change your riskObesity-related OSA or knee osteoarthritis where GLP-1s can treat upstream weight and symptoms
Have we done the foundations?
Nutrition you can actually live with
Sleep and circadian rhythm dialed
Movement plan, including resistance training and aerobic work
If we use a GLP-1, how do we do it intelligently?
Awareness of rare GI, gallbladder, pancreas risks and known warnings
Open monitoring of mood, libido, and compulsive behaviors
Protecting muscle mass with lifting and protein
The message I want patients to internalize:
GLP-1s are powerful tools for the right person at the right time. They’re neither miracle drugs nor villains. The real work is matching them to the right patient, at the right risk level, while still doing the unglamorous basics—sleep, nutrition, movement, and mental health.
