How Do GLP-1 Medications Compare to HRT for Weight Loss?

SAs women enter menopause, hormonal shifts can make maintaining a healthy weight more challenging. Many women notice slower metabolism, changes in fat distribution (especially around the abdomen), and increased difficulty losing weight — even with the same diet and exercise routine. Today, two types of medications are often discussed in this context: GLP-1 medications, such as semaglutide (Ozempic®, Wegovy®) or tirzepatide (Zepbound®), and hormone replacement therapy (HRT), commonly prescribed to relieve menopause symptoms. While both treatments may influence body weight, they work in very different ways. This article explores how GLP-1 medications compare to HRT for weight loss, especially for women over 50.

Active Ingredient: Semaglutide

The active ingredient, Semaglutide, is a GLP-1 receptor agonist only. It mimics the hormone GLP-1, which helps regulate blood sugar and appetite.

Active Ingredient: Tirzepatide

The active ingredient, Tirzepatide, is a dual agonist — it activates GLP-1 receptors and GIP (glucose-dependent insulinotropic polypeptide) receptors. The added GIP activity may enhance weight loss and blood sugar control compared to GLP-1–only drugs.

Key Takeaways

• GLP-1 medications are originally diabetes drugs that now play a major role in medical weight management.

• HRT primarily treats menopause symptoms (like hot flashes, mood swings, and bone loss), but it can indirectly support healthy metabolism.

• GLP-1s typically produce significant weight loss, while HRT mainly helps prevent weight gain related to estrogen decline.

• The right choice depends on individual goals, menopausal symptoms, and overall health history.

What Are GLP-1 and HRT Drugs?

GLP-1 medications

GLP-1 (glucagon-like peptide-1) receptor agonists are injectable or oral medications that mimic a natural hormone involved in blood sugar and appetite regulation. They include:

• Semaglutide (Ozempic®, Wegovy®, Rybelsus®)

• Tirzepatide (Mounjaro®, Zepbound®)

• Liraglutide (Saxenda®, Victoza®)

Originally developed for type 2 diabetes, GLP-1s are now FDA-approved for chronic weight management. They help users feel full sooner, reduce cravings, and improve insulin sensitivity — all of which support sustained weight loss.

HRT (Hormone Replacement Therapy)

HRT provides estrogen (and sometimes progesterone or testosterone) to replace declining hormone levels during menopause. It’s primarily prescribed to reduce hot flashes, night sweats, mood changes, and vaginal dryness, and to protect bone density.

While HRT is not a weight-loss medication, it may indirectly influence metabolism and fat distribution by restoring hormonal balance disrupted during menopause.

A brief history

• GLP-1 drugs were introduced in the early 2000s for diabetes and gained major attention after 2021 when semaglutide and tirzepatide were shown to cause 15–20% average body-weight reduction.

• HRT has been used for decades and remains a standard therapy for menopausal symptom relief, though its popularity dipped after early 2000s safety concerns before later studies clarified its risks and benefits.

GLP-1 and HRT Drugs: Mechanism of Action for Weight Loss

How GLP-1s work

GLP-1 medications mimic the gut hormone GLP-1, which:

• Slows stomach emptying, helping you feel full longer

• Reduces appetite and food cravings

• Enhances insulin release and stabilizes blood sugar

• Improves energy metabolism

Together, these mechanisms lead to reduced calorie intake and gradual, steady weight loss.

How HRT affects weight

During menopause, dropping estrogen levels can:

• Slow metabolism

• Increase fat storage, especially around the abdomen

• Reduce lean muscle mass

By restoring estrogen, HRT may help:

• Prevent or reduce abdominal fat gain

• Improve insulin sensitivity

• Maintain muscle tone and bone health

However, HRT’s impact is more about stabilizing weight and metabolic health, not producing significant fat loss.

Comparing both

• GLP-1s: Directly target appetite, blood sugar, and calorie intake.

• HRT: Addresses the hormonal environment that contributes to weight gain during menopause.

In short: GLP-1s cause weight loss, while HRT helps minimize menopausal weight gain.

GLP-1 vs HRT: Weight-Loss Results

GLP-1 results

In major trials:

• Semaglutide (Wegovy®) users lost an average of 15% of body weight over 68 weeks.

• Tirzepatide (Zepbound®) achieved even greater results — up to 21% body-weight reduction in some participants.

• Benefits are sustained when lifestyle changes are maintained alongside treatment.

HRT results

Research on HRT and weight loss shows modest effects:

• Some studies show slower fat accumulation and better body-composition outcomes in women taking estrogen therapy compared to those not on HRT.

• However, HRT alone does not cause significant weight loss. Its effect is primarily weight stabilization, not reduction.

• Women on HRT may find it easier to maintain weight and avoid menopausal belly fat compared to women without treatment.

Bottom line

GLP-1 drugs have clinically proven weight-loss effects, while HRT’s metabolic benefits are supportive but secondary.

GLP-1 and HRT Side Effects for Women After 50

Side effects of GLP-1s

Common:

• Nausea, vomiting, or constipation

• Fatigue or dizziness

• Mild hair shedding

Serious but rare:

• Gallbladder disease, pancreatitis, or thyroid-related risks

Most effects are temporary and improve with gradual dose titration.

Side effects of HRT

Common:

• Breast tenderness, bloating, or mood changes

• Mild fluid retention

Potential long-term risks (depend on type, dose, and duration):

• Increased risk of blood clots or stroke (especially oral estrogen)

• Possible breast-cancer risk with long-term combined HRT

Transdermal (patch, gel) forms may carry lower clot risk than oral pills.

Comparison

• GLP-1s: More effective for weight loss; side effects are mostly gastrointestinal.

• HRT: Mild weight stabilization benefits; side effects relate to hormone levels and cardiovascular risks.

What Medication to Choose for Weight Loss if You Are a Woman in Menopause

If your main goal is weight loss, GLP-1 medications are typically more effective and evidence-based.
If your primary concern is menopause symptom relief, HRT may be the better first step — with added benefits of preventing weight gain and improving metabolic balance.

Consider:

Talk to your doctor about:

• Your current weight, BMI, and metabolic profile

• Menopause symptoms (sleep, mood, bone health)

• Past medical history (heart, thyroid, cancer risk)

• Possible combination therapy — some women benefit from both HRT and GLP-1s under supervision

A telehealth provider like Heally can assess your symptoms, goals, and lab results to help determine whether GLP-1 medication, HRT, or a combination is right for you.

If you want to explore your eligibility for GLP-1 or GIP/GLP-1 treatments today, Heally can connect you to a licensed provider who helps assess your situation and determine whether one of the approved drugs might be right for you. Schedule a free consultation and let us help you plan what’s safe, effective, and accessible now.

Conclusion

GLP-1 medications and HRT address two very different problems — but for women over 50, they can both play valuable roles in improving overall health and well-being.

• GLP-1s offer clinically proven, significant weight loss and metabolic benefits.

• HRT primarily manages menopausal symptoms while supporting hormonal balance and preventing fat accumulation.

For many women, the best approach may be personalized, combining hormone optimization with modern metabolic medications — under the care of a qualified clinician.

Sources

• American Diabetes Association: Standards of Medical Care in Diabetes, 2025
• New England Journal of Medicine: Once-Weekly Semaglutide in Adults with Overweight or Obesity
• Harvard Health Publishing: GLP-1 diabetes and weight-loss drug side effects: “Ozempic face” and more
• Metabolism Clinical and Experimental: Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause
• JCEM: Effect of Postmenopausal Hormone Therapy on Body Weight and Waist and Hip Girths
• University of Illinois Chicago: What efficacy data are available on the use of tirzepatide for obesity?
• Reuters: Novo Nordisk says its obesity drug in higher dose shows 20.7% weight loss
• PubMed Central: The History of Estrogen Therapy
• ScienceDirect ELSEVIER: Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss: A Review of Central and Peripheral Pathways in Appetite and Energy Regulation
• Women’s Health Reports: Adverse Changes in Body Composition During the Menopausal Transition and Relation to Cardiovascular Risk: A Contemporary Review
• WILEY BioMed Research International: Estrogen Deficiency and the Origin of Obesity during Menopause
• PubMed Central: Body composition and cardiometabolic health across the menopause transition
• JAMA Network: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial
• PubMed Central: Influence of Menopausal Hormone Therapy on Body Composition and Metabolic Parameters
• New England Journal of Medicine: Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
• PubMed Central: Impact of hormone replacement therapy on the body mass and fat compositions of menopausal women: a cross-sectional study
• NHS: Side effects of hormone replacement therapy (HRT)Hormone Therapy for Menopause Symptoms

1. FDA Label: OZEMPIC (Semaglutide Injection) Medication Guide
2. FDA Label: WEGOVY (Semaglutide Injection) Medication Guide
3. FDA Label: RYBELSUS (Oral Semaglutide) Medication Guide

1. FDA Label: MOUNJARO (Tirzepatide Injection) Medication Guide
2. FDA Label: ZEPBOUND (Tirzepatide Injection) Medication Guide

Liraglutide FDA Labels:

1. FDA Label: VICTOZA (Liraglutide Injection) Medication Guide
2. FDA Label: SAXENDA (Liraglutide Injection) Medication Guide

Important Medical Information and Disclaimers

Compounded Drug Warning

Individual Results May Vary

Common side effects of GLP-1 medications may include:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Stomach pain or discomfort
• Decreased appetite
• Indigestion or gas
• Redness, itching, or soreness at the injection site

Most side effects are mild to moderate and may improve as your body adjusts to treatment. If you experience severe or persistent symptoms, contact your healthcare provider promptly.

Boxed Warning (Thyroid C-Cell Tumor Risk)

GLP-1 receptor agonists, including semaglutide, carry an FDA boxed warning regarding the potential risk of thyroid C-cell tumors. Do not use if you or a family member has a history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
When to Seek Immediate Medical Attention
Contact your healthcare provider or seek emergency care if you experience:

• Severe abdominal pain that does not go away
• Signs of an allergic reaction (rash, swelling, difficulty breathing)
• Symptoms of pancreatitis (severe abdominal pain, vomiting)
• Symptoms of severe dehydration (dizziness, confusion, rapid heartbeat)

FDA Adverse Event Reporting

To report medication side effects to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also contact the medication’s manufacturer directly.