THE COMPLETE MEN'S GUIDE TO GLP-1 MEDICATIONS

WHAT ARE GLP-1 MEDICATIONS?

GLP-1 medications are a class of drugs that mimic a hormone your body naturally produces called glucagon-like peptide-1. When you eat, your gut releases GLP-1, which tells your pancreas to release insulin and tells your brain you're full. These medications amplify that signal — dramatically.

The result is reduced appetite, slower gastric emptying (food sits in your stomach longer), and for most people, significant weight loss. Clinical trials consistently show 15-22% total body weight loss over 12-18 months — results that were essentially impossible with previous weight loss medications.

There are currently two main GLP-1 medications used for weight loss:

Semaglutide (brand names: Wegovy for weight loss, Ozempic for diabetes) is a pure GLP-1 agonist. It's been on the market longer and has the most safety data, including cardiovascular protection studies.

Tirzepatide (brand names: Zepbound for weight loss, Mounjaro for diabetes) is a dual GLP-1/GIP agonist — it targets two hormone receptors instead of one. It's newer, more powerful, and in head-to-head trials produces more weight loss.

SEMAGLUTIDE VS TIRZEPATIDE: THE REAL COMPARISON

Until recently, comparing these drugs required extrapolating across different trials. That changed with SURMOUNT-5, the first head-to-head study comparing Zepbound (tirzepatide) to Wegovy (semaglutide) in adults with obesity.

The results were definitive: tirzepatide produced 20.2% mean weight loss compared to 13.7% for semaglutide over 72 weeks. That's a 47% relative advantage for tirzepatide. The gap was even larger at higher weight loss thresholds — significantly more tirzepatide patients hit 20% and 25% total body weight loss.

Factor	Semaglutide (Wegovy)	Tirzepatide (Zepbound)
Weight Loss	~15% (14.9% in STEP 1)	~21% (20.2% in SURMOUNT-5)
Mechanism	GLP-1 only	GLP-1 + GIP (dual agonist)
CV Data	SELECT trial: 20% MACE reduction	CV outcomes trial ongoing
Max Dose	2.4 mg weekly	15 mg weekly
Titration	16 weeks to max dose	20 weeks to max dose
Brand Cost	~$1,300/month	~$1,000/month

Which should you choose? If maximum weight loss is the priority (BMI >40, or you need significant loss for surgery clearance), tirzepatide is statistically more likely to get you there. If you have established cardiovascular disease, semaglutide currently has stronger evidence for heart protection (the SELECT trial showed a 20% reduction in heart attacks, strokes, and cardiovascular death). If you plateau on semaglutide, switching to tirzepatide often breaks through the stall.

TESTOSTERONE: WHAT ACTUALLY HAPPENS

This is the question men ask most: "Will this tank my testosterone?" The research says the opposite — for obese men, GLP-1s typically restore testosterone, not lower it.

The ENDO 2025 study from Saint Louis University tracked 110 men with obesity on GLP-1 medications for 18 months. The proportion of men with normal testosterone rose from 53% to 77% following approximately 10% body weight loss. Total testosterone increased from 312 ng/dL to 368 ng/dL (P<.001).

Why does this happen? Obesity and low testosterone create a vicious cycle. Fat tissue contains an enzyme called aromatase that converts testosterone to estrogen. More body fat means more aromatase, which means less testosterone. The elevated estrogen also signals your brain to produce less testosterone. GLP-1s break this cycle by reducing fat mass, which reduces aromatase activity, which allows testosterone to normalize.

What About Fertility?

This is where GLP-1s have a major advantage over testosterone replacement therapy. A Ljubljana study (2024) randomized 25 men with type 2 diabetes and low testosterone to either semaglutide or injectable TRT. The critical finding: semaglutide improved sperm morphology from 2% to 4% normal forms, while TRT significantly decreased sperm concentration and total count.

If you're planning to have kids, GLP-1s offer a fertility-preserving path to weight loss that TRT cannot.

MUSCLE PRESERVATION: THE HONEST NUMBERS

Let's be direct: rapid weight loss always involves some muscle loss. With GLP-1s alone, roughly 25-40% of weight lost is lean mass. That's not great, but it's also not unusual — it's similar to what happens with any rapid weight loss method including bariatric surgery.

The good news: you can significantly improve this ratio with the right approach, and new combination therapies are showing remarkable results.

The BELIEVE trial combined semaglutide with bimagrumab (a myostatin inhibitor) and achieved 22.1% total weight loss with 92.8% coming from fat mass — compared to just 71.8% with semaglutide alone. That's 67% better muscle preservation. While bimagrumab isn't commercially available yet, this proves the muscle loss isn't inevitable — it's a problem being solved.

How to Preserve Muscle Now

1. Prioritize Protein. Research suggests 1.6-2.3 g/kg of body weight daily. An 86% majority of GLP-1 patients don't hit adequate protein targets due to reduced appetite. If solid food is difficult, use whey protein isolate shakes.

2. Resistance Training. 2-3 sessions per week of compound movements (squats, deadlifts, presses, rows). You don't need to train like a bodybuilder — you need to give your body a reason to keep muscle while in a caloric deficit.

3. Don't Rush. Faster weight loss typically means more muscle loss. The standard titration schedule exists partly for this reason — gradual loss is healthier loss.

CARDIOVASCULAR BENEFITS

This is the data that transformed how doctors view GLP-1s — they're not just weight loss drugs, they're cardioprotective.

The SELECT trial enrolled 17,604 patients with obesity and established cardiovascular disease — but without diabetes. Over 39.8 months, semaglutide 2.4mg reduced major adverse cardiovascular events by 20% compared to placebo. Benefits appeared within 3 months. This led to FDA approval in March 2024 for cardiovascular risk reduction — the first weight loss drug ever approved for this indication.

The cardiovascular benefits go beyond what you'd expect from weight loss alone. GLP-1s reduce inflammation (measured by CRP), improve blood vessel function, and may directly protect heart muscle cells.

SIDE EFFECTS: WHAT TO EXPECT

GLP-1s are generally safe, but they have a distinct side effect profile that's predominantly gastrointestinal. In clinical trials:

• Nausea: 44% of participants (most common)
• Diarrhea: 30%
• Vomiting: 24%
• Constipation: 24%

These effects are typically transient, peaking during the first 2-3 days after a dose increase and subsiding as your body adjusts. The titration schedule exists specifically to minimize these effects — rushing it significantly increases the risk of severe symptoms and treatment abandonment.

Management Strategies That Work

The Volume Rule: Because gastric emptying is slowed, your stomach can't handle large volumes. Shift from 3 large meals to 5-6 small, nutrient-dense meals. Overeating is the fastest route to nausea.

Fat Content: High-fat foods take longer to digest naturally. Combined with GLP-1s, they can sit in your stomach for hours, causing bloating, sulfurous burps, and reflux. Many patients need to reduce fat intake significantly — not for calories, but for comfort.

Hydration: Nausea leads to reduced fluid intake, which causes dehydration, which worsens nausea and causes constipation. Aim for 2-3 liters of water daily. Consider electrolyte supplements if intake is difficult.

DOSING SCHEDULES

Both medications follow a "start low, go slow" approach to minimize side effects. The titration schedule is not optional — it's a safety protocol.

Key difference: Tirzepatide offers more "parking spots." Many patients achieve substantial weight loss at 5, 7.5, or 10 mg and never need to escalate to 15 mg. This flexibility is useful for managing side effects.

WHAT IT ACTUALLY COSTS

Let's be honest about pricing — these are expensive medications, and the cost landscape is complicated.

Brand-Name Pricing

Without insurance, Wegovy runs approximately $1,300/month and Zepbound approximately $1,000/month. With good insurance coverage that includes weight loss medications, copays can be $25-100/month. Without coverage, you're paying cash.

Compounded Alternatives

Compounded semaglutide typically costs $150-400/month through telehealth providers. Compounded tirzepatide ranges from $300-600/month. These are significantly cheaper, but come with important caveats:

Saving Money

HSA/FSA: GLP-1 prescriptions are generally eligible for Health Savings Account and Flexible Spending Account payment, letting you pay with pre-tax dollars.

Manufacturer Programs: Novo Nordisk and Eli Lilly offer savings programs for eligible patients — check their websites directly.

Coming Soon: Oral semaglutide 25mg was FDA-approved December 2025 at an expected price of $149/month — significantly cheaper than injectable. It launches January 2026.

HOW TO GET STARTED

Eligibility

Most providers follow FDA label criteria: BMI ≥30 (obese) OR BMI ≥27 (overweight) with at least one weight-related condition such as high blood pressure, high cholesterol, type 2 diabetes, or sleep apnea. All require a telehealth or in-person consultation with a licensed physician.

Telehealth vs. Traditional Doctor

Both routes work. Telehealth is typically faster (same-week appointments common), may be cheaper (subscription models often include medication), and is more convenient. Traditional doctors may offer more comprehensive care and can handle complex medical situations. Many men use telehealth to start and transition to a primary care physician for long-term management.

THE BOTTOM LINE

GLP-1 medications represent a genuine breakthrough in weight loss treatment. For men specifically, the data is encouraging:

• Testosterone typically improves — 77% of obese men with low T normalized after treatment
• Fertility is preserved — unlike TRT, which suppresses sperm production
• Cardiovascular protection is real — 20% reduction in heart attacks and strokes
• Muscle loss can be minimized — with proper protein intake and resistance training
• Side effects are manageable — mostly GI, mostly temporary, mostly related to eating too much or too fast

These medications aren't magic — they still require lifestyle changes to work optimally. But they fundamentally shift what's possible for men who've struggled with weight loss. For the first time, there's a medical treatment that works with your biology instead of against it.

The questions to ask yourself: Is the cost manageable? Am I willing to commit to injections and the titration process? Do I have realistic expectations about the timeline and effort involved?

If the answers are yes, GLP-1s may be worth discussing with a doctor.