GLP‑1 Drugs for Obesity and Weight Loss (2025): A Full Guide with ScriptScores™

Slug: glp-1-weight-loss-2025-scriptscores
Meta: Evidence-based overview of GLP‑1 and GIP/GLP‑1 medications for weight management: how they work, who qualifies, expected results, risks, long‑term use, costs, and our ScriptScores™ for each option.

This article is informational and not medical advice. Talk to a licensed clinician before starting or stopping any medication.

TL;DR

• Weekly GLP‑1/GIP‑GLP‑1 injections reduce appetite, slow gastric emptying, and improve insulin signaling, which helps you eat less without feeling as hungry.

• Average loss at clinically approved doses: ~15% of body weight with semaglutide 2.4 mg (Wegovy), ~16–22% with tirzepatide (Zepbound), and ~8% with liraglutide 3 mg (Saxenda), alongside diet and activity.

• Labels include a boxed warning about thyroid C‑cell tumors in rodents; avoid use with personal/family history of MTC or MEN2.

• New indications expand benefits: Wegovy now carries approvals for cardiovascular risk reduction and MASH (noncirrhotic, F2–F3 fibrosis); Zepbound is also approved for obstructive sleep apnea in adults with obesity.

• Coverage is improving for selected indications, but access and out‑of‑pocket costs vary by plan.

ScriptScores™: How we rate these meds

Scale: 0–100 (higher is better).
Weights: Efficacy 50% · Safety/Tolerability 20% · Evidence Strength 20% · Access/Affordability 10%.

The scores reflect published efficacy, labeled safety, breadth of supporting trials, and current U.S. coverage patterns. They are editorial, not clinical directives.

What GLP‑1 and GIP/GLP‑1 drugs are

GLP‑1 receptor agonists were built for type 2 diabetes control and later adapted for chronic weight management. Tirzepatide targets both GIP and GLP‑1 receptors, which appears to add to appetite control and weight loss. All approved weight‑management products are injectables supplied in prefilled pens.

How they reduce weight

• Heighten satiety signals in the brain

• Slow stomach emptying

• Improve post‑meal insulin response and blunt glucose swings

People often report less intrusive food thoughts (“food noise”) and a shift away from hyper‑palatable foods. Effects build gradually as doses increase.

Who qualifies

Approved for:

• Adults with BMI ≥30, or BMI ≥27 with a weight‑related condition (e.g., hypertension, dyslipidemia, sleep apnea, cardiovascular disease, type 2 diabetes)

• Adolescents 12+ with obesity for Wegovy and Saxenda (per labels; specifics vary)

Do not use if you or family have medullary thyroid carcinoma (MTC) or MEN2, or if you’ve had a serious hypersensitivity to the active drug. Pregnancy: not recommended. Severe GI disease: not recommended. Your clinician will screen for pancreatitis history, gallbladder disease, and medication interactions.

What results to expect

With lifestyle support (nutrition, activity, sleep, alcohol limits), pivotal trials reported:

• Semaglutide 2.4 mg (Wegovy): ~15% average loss by week 68; many reach ≥15%.

• Tirzepatide (Zepbound): ~16–22% average loss by week 72 depending on dose.

• Liraglutide 3 mg (Saxenda): ~8% average loss by week 56.

Results vary. A minority lose <5%. Some discontinue due to side effects. Visceral fat and liver fat tend to drop with effective therapy.

Benefits beyond weight

• Cardiovascular risk: Wegovy lowers major CV events in adults with overweight/obesity and established CV disease.

• Liver health: Wegovy has an accelerated approval to treat MASH with F2–F3 fibrosis in non‑cirrhotic adults.

• Sleep apnea: Zepbound treats moderate‑to‑severe OSA in adults with obesity.

• Metabolic markers: Typical improvements include lower A1c, fasting glucose, triglycerides, and systolic BP.

Risks and side effects

Common (dose‑related): nausea, vomiting, diarrhea, constipation, belching, abdominal pain or bloating, reflux/heartburn, fatigue. These are most noticeable after starting or stepping up a dose.

Less common but serious:

• Gallbladder disease (e.g., cholelithiasis, cholecystitis)

• Pancreatitis

• Acute kidney injury (often from dehydration during severe GI symptoms)

• Intestinal obstruction (ileus) warning on semaglutide

• Hypoglycemia when combined with insulin or sulfonylureas

• Allergic reactions up to anaphylaxis (rare)

Boxed warning: risk of thyroid C‑cell tumors in rodents; avoid with MTC/MEN2.

Cosmetic changes: Rapid fat loss can unmask volume loss in the face or buttocks and may lead to looser skin. These are effects of weight loss itself, not a direct drug toxicity.

Dosing and titration (typical)

• Wegovy: 0.25 mg weekly ×4 weeks → 0.5 mg ×4 → 1.0 mg ×4 → 1.7 mg ×4 → 2.4 mg weekly maintenance (some remain at 1.7 mg if effective/tolerable).

• Zepbound: 2.5 mg weekly ×4 → escalate by 2.5 mg every ≥4 weeks to 5/10/15 mg maintenance per response and tolerability. OSA maintenance is typically 10 or 15 mg.

• Saxenda: Daily injection titrated weekly to 3.0 mg/day.

Your clinician can pause or reduce the dose if side effects spike.

Long‑term use and stopping

Obesity is chronic. When treatment stops, hunger and weight often rebound. In extension data, participants regained a meaningful portion of lost weight after withdrawing semaglutide. The best hedge: build durable habits during treatment—adequate protein, resistance training 2–3×/week, sleep, and activity—so you keep more of the loss if you pause meds.

Costs, coverage, and access

• Medicare Part D may cover Wegovy for cardiovascular risk reduction in adults with established CVD; not for weight loss alone. Prior authorization is common.

• Commercial plans vary widely and may require documentation, step therapy, and stop rules.

• Compounded products: not FDA‑approved. The FDA has reported dosing errors and counterfeit risks. Use only if medically justified and dispensed by a licensed compounding pharmacy, and only when FDA‑approved products are unavailable.

Ways to stretch value (ethically): titrate slowly to reduce wasted pens, align nutrition/training/sleep to improve “results per dose,” use manufacturer support if eligible, and verify pharmacy sourcing.

Alternatives

• Other prescription anti‑obesity meds: orlistat, phentermine‑topiramate, naltrexone‑bupropion. Less average weight loss but lower cost for some.

• Metabolic/bariatric surgery: highest and most durable average loss with broad metabolic benefits; invasive but often covered.

• Lifestyle programs: low‑carb or Mediterranean‑style patterns plus structured resistance and aerobic training.

Provider checklist (use at your consult)

• Am I a candidate based on BMI and comorbidities? Which option fits my history?

• What titration plan will we use, and how do we manage nausea/constipation?

• How will we monitor A1c, lipids, BP, gallbladder, and retinopathy risk if relevant?

• What are realistic 3‑, 6‑, and 12‑month targets and stop rules?

• What’s the plan for maintenance and for a safe pause if needed?

Bottom line

• Zepbound leads on average weight loss and adds an OSA indication.

• Wegovy pairs strong weight loss with CV risk‑reduction and MASH (F2–F3) treatment approvals.

• Saxenda remains a daily, lower‑efficacy option when weeklies are unsuitable.
  Use approvals, access, and your health history to pick the right fit—and focus on habits during treatment to protect results long term.