Compounded Semaglutide vs Tirzepatide: Which Is Better for Midlife Women?

If you’re a woman in your 30s, 40s, 50s, or 60s, you’ve likely heard about GLP-1 medications being used for weight, cravings, and energy balance. With so many names in circulation — semaglutide, tirzepatide, compounded injections, dissolvable tablets — it can feel difficult to sort out which option is appropriate for you.

Both semaglutide and tirzepatide are effective, but they differ in how they act in the body, the clinical evidence supporting them, and the forms in which they are available. It’s also important to distinguish between FDA-approved medications and compounded versions, which are not regulated in the same way.

This guide outlines the key differences, clinical evidence, and safety considerations, so that women in midlife can make informed decisions with their healthcare provider.

Josie’s TL;DR

• Semaglutide is FDA-approved in several brand forms (Ozempic®, Wegovy®, Rybelsus®). Compounded semaglutide is available but not FDA-approved.
• Tirzepatide is FDA-approved for type 2 diabetes (Mounjaro®) and obesity (Zepbound®). Oral tirzepatide is not yet FDA-approved; compounded tirzepatide versions are experimental, and not FDA-approved
• Clinical trials (STEP for semaglutide, SURMOUNT-1 for tirzepatide) show both support weight loss, with tirzepatide producing stronger results on average.
• Both drugs have potential side effects and contraindications. Compounded versions may carry added risks of variable strength and purity.
• Lifestyle measures, hormone therapy, and other strategies remain important tools for midlife weight management alongside medication.
• Your Josie provider will recommend the right fit based on your symptoms, history, and goals

What’s the Core Difference Between Compounded Semaglutide and Compounded Tirzepatide?

Compounded semaglutide and compounded tirzepatide are both GLP-1 medications that help regulate appetite, cravings, and blood sugar. The key difference is how they work inside your body.

• Compounded semaglutide mimics one hormone: GLP-1.
• Compounded tirzepatide mimics two: GLP-1 and GIP.

This dual mechanism appears to increase appetite suppression and weight loss potential. In the STEP trials, semaglutide produced meaningful reductions in weight among people with obesity. In the SURMOUNT-1 trial, tirzepatide led to even greater average weight loss compared with semaglutide, although both were effective.

For midlife women, this means compounded tirzepatide may feel stronger, particularly when weight gain is linked to insulin resistance or hormonal changes. Compounded semaglutide may be a gentler option, especially for those new to GLP-1 medications or sensitive to gastrointestinal side effects.

Key distinctions at a glance:

• Compounded semaglutide: GLP-1 only
• Compounded tirzepatide: GLP-1 + GIP
• Both support appetite control and blood sugar balance
• Tirzepatide may feel stronger or work faster for some
• Semaglutide is often better tolerated at lower starting doses

Want to go deeper on each option?

• Everything You Need to Know About Compounded Semaglutide for Midlife Women
• What Midlife Women Should Know About Compounded Tirzepatide

Considering Midlife Hormonal Changes

Weight management during perimenopause and menopause is complex. Estrogen decline can increase fat storage, raise insulin resistance, and intensify cravings. These shifts mean some women respond differently to medications.

• Semaglutide may be a steady entry point for women experiencing early appetite changes, fatigue, or digestive sensitivity.
• Tirzepatide may help those struggling with persistent cravings or more pronounced insulin resistance.

However, medications are only one part of the picture. Evidence supports the role of balanced nutrition, physical activity, stress management, and adequate sleep in midlife weight health. In some cases, hormone replacement therapy (HRT) may also be considered as part of a broader strategy for symptom and weight management.

Safety, Side Effects, and Contraindications

Both compounded semaglutide and tirzepatide share a common side effect profile, particularly in the early stages:

• Nausea
• Constipation or diarrhea
• Fatigue
• Headaches
• Appetite suppression that may feel too strong initially

For most, these effects improve with time and dose adjustments. However, important safety considerations include:

• Avoid use if you or your family have a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2).
• Caution in individuals with a history of pancreatitis or severe gastrointestinal disease.
• Long-term safety is still being studied, though semaglutide has demonstrated cardiovascular benefit in trials, while tirzepatide’s long-term cardiovascular outcomes are under evaluation.

Compounded medications are sometimes used during drug shortages, but unlike brand-name versions, they are not FDA-approved. Their purity and strength may vary by pharmacy, and oversight is limited. This is an important distinction for women considering compounded options.

Oral vs Injectable — What Formats Are Available?

At Josie, both compounded semaglutide and compounded tirzepatide are available in two formats:

• Oral dissolvable tablets (taken daily)
• Injectable medications (taken weekly)

This gives you flexibility to start where you’re most comfortable and switch if your needs change.

We offer compounded oral tirzepatide and compounded oral semaglutide, as well as our premium, personalized GLP-1 medication.

Learn the difference, and which is better for you - Compounded GLP-1 oral or injectable.

Why Women Love Having Both Options:

• Oral is great for needle aversion or gentle starts
• Injectable is convenient (one dose per week) and may lead to stronger appetite control
• Some women begin with oral for a soft landing, then transition to injectables when ready

At Josie, your provider helps you decide what’s best based on your symptoms, goals, and lifestyle. There’s no one-size-fits-all plan — and no pressure to choose one format forever.

Oral vs Injectable Options

Currently, the FDA has approved:

• Oral semaglutide: Rybelsus® (daily tablet).
• Injectable semaglutide: Ozempic® (weekly injection for diabetes) and Wegovy® (weekly injection for obesity).
• Injectable tirzepatide: Mounjaro® (diabetes) and Zepbound® (obesity).

At present, oral tirzepatide is not FDA-approved. Any oral versions offered through compounding pharmacies are considered experimental.

Injectables remain the most studied and commonly prescribed format. Some individuals find weekly injections more convenient, while others prefer daily oral dosing if available and appropriate.

Why Women Love Having Both Options:

• Oral is great for needle aversion or gentle starts
• Injectable is convenient (one dose per week) and may lead to stronger appetite control
• Some women begin with oral for a soft landing, then transition to injectables when ready

At Josie, both compounded semaglutide and compounded tirzepatide are available in two formats:

• Oral dissolvable tablets (taken daily)
• Injectable medications (taken weekly)

This gives you flexibility to start where you’re most comfortable and switch if your needs change.

We offer compounded oral tirzepatide and compounded oral semaglutide, as well as our premium, personalized GLP-1 medication.

Learn the difference and find out which is better for you - Compounded GLP-1 oral or injectable.

Real Stories: What It Looks Like to Start on the Right One

There’s no perfect answer — but when women get matched to the right option based on symptoms, goals, and provider insight, everything just clicks.

Meet Dana, 56 - Compounded Semaglutide Injections

Dana was postmenopausal, struggling with relentless cravings, and felt defeated after trying low-carb diets for years. Her Josie quiz results flagged fatigue, sensitive digestion, and past trouble with appetite suppressants.

After reviewing her intake, the Josie care team recommended compounded semaglutide injections with a slow start.

“The biggest shift for me was mental. I wasn’t starving. I wasn’t crashing mid-morning. It felt gentle, but it worked.”

Within 4 weeks, Dana noticed fewer blood sugar crashes and more consistent energy — all without nausea or bloat. Her provider gradually increased her dose as her body adjusted.

Meet Camille, 45 - From Oral to Injectable Compounded Tirzepatide

Camille came to Josie already set on oral compounded tirzepatide. She was needle-averse, and the idea of a dissolvable tablet felt approachable and easy to stick with.

She gave it a real shot — but after a couple of months, she wasn’t seeing the results her friends were getting on Josie’s injectable version. After a conversation with her provider, she decided to try switching.

“I was terrified of injections, but it’s actually really simple. Just once a week, and I don’t even think about it anymore.”

Now on compounded tirzepatide injections, Camille’s energy has improved, and her appetite is much easier to manage. Getting over her needle fear unlocked the results she was hoping for.

Both Dana and Camille took different paths, but both found their stride with Josie’s personalized, flexible approach.

Which One Should You Start With?

The decision between semaglutide and tirzepatide should always be guided by a healthcare provider, taking into account:

• Health history and contraindications
• Current symptoms and hormone status
• Past response to weight loss strategies
• Comfort with oral vs injectable dosing

In general:

• Semaglutide may suit women seeking a gradual, well-tolerated entry point.
• Tirzepatide may be considered when stronger appetite regulation or greater weight reduction is needed.

Neither should replace the foundation of lifestyle measures such as nutrition, activity, and sleep. In some midlife cases, HRT or other interventions may be part of the broader plan.

At Josie, your quiz responses guide the recommendation — and your provider helps adjust the dose based on how you feel, not just a schedule.

The best place to start is with a provider who listens — and a medication that’s built around your body. Take our quiz to get started.

FAQs: Semaglutide vs Tirzepatide

Are both options available as injections and orals?

Semaglutide is FDA-approved in both injectable and oral forms. Tirzepatide is FDA-approved only in injectable form; oral tirzepatide is not yet approved. Compounded versions are not FDA-approved, but are available in both oral and injectable forms.

Which one is better for menopause weight gain?

Both have been effective in clinical trials. Tirzepatide has shown greater average weight loss in SURMOUNT-1, but responses vary. Lifestyle, hormonal factors, and tolerance play a major role.

Are compounded versions the same as brand names?‍

No. Compounded versions are not FDA-approved, may vary in quality, and should be used cautiously, often only when brand versions are unavailable.

Are side effects the same for both?

Not exactly. Nausea, fatigue, and digestive issues are common for both, but tirzepatide can feel stronger. Compounded options allow for slower dose increases, which may reduce intensity.

What safety risks should I be aware of?

Avoid if there is a personal or family history of medullary thyroid cancer or MEN2. Use caution with pancreatitis or severe stomach disease. Long-term safety is still under study.

Can I switch if the first one doesn’t work well?

Yes. Many women adjust their approach with their provider, including changing medications or dosing formats, based on results and tolerance.

How do I know which one I’ll get?

Your provider recommends the best option after reviewing your quiz answers, health history, and goals. The choice is personalized — not one-size-fits-all.

Final Thoughts

Semaglutide and tirzepatide are valuable tools for weight management in midlife, supported by strong trial data. Tirzepatide has demonstrated greater average weight loss, while semaglutide has more established long-term safety data.

Compounded options may be available, but they are not FDA-approved and should be approached carefully. For midlife women, the best strategy is a personalized plan that combines medical guidance, safe prescribing, and ongoing lifestyle support.

Resources

• FDA: Zepbound (tirzepatide) approval for weight management
• FDA: Wegovy (semaglutide) cardiovascular benefit approval
• NEJM: STEP trial – Once-Weekly Semaglutide in Adults with Overweight or Obesity
• NEJM: SURMOUNT-1 trial – Tirzepatide Once Weekly for the Treatment of Obesity
• Nature Medicine: Two-year effects of semaglutide in adults with overweight or obesity (STEP-5 trial)
• FDA: Risks with compounded semaglutide products
• ‍FDA: Concerns about unapproved GLP-1 products