💬 GLP-1 and GIP/GLP-1 Receptor Agonists in Obesity & Type 2 Diabetes (2025 Update)

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By Dr. Sk Sabir Rahaman, MBBS, MD (Pharmacology), DFM(Family Medicine), FCFM, CCEBDM, CCLSD 

📍 Specialist Family Physician | Consultant Pharmacologist | Lifestyle & Diabetes Expert


Understanding Semaglutide, Tirzepatide, and the Debate About Weight Regain

🧠 1. Why Everyone’s Talking About These Drugs

In just a few years, GLP-1 receptor agonists (like semaglutide) and the newer dual GIP/GLP-1 agonist (tirzepatide) have reshaped how we treat obesity and type 2 diabetes (T2DM).

They do much more than lower blood sugar — they suppress appetite, slow digestion, and help the body use insulin more efficiently.
The result: major, sustained weight loss and better metabolic health while on treatment.

  • Semaglutide 2.4 mg: typically 10–15% average body weight loss in trials.

  • Tirzepatide: often 15–20% or more — the highest seen in modern studies.

  • SELECT trial: proved semaglutide even reduces heart attacks and strokes in obese people without diabetes.

⚙️ 2. How They Work — The Incretin Boost

  • GLP-1 receptor agonists mimic the natural hormone GLP-1, which helps the pancreas release insulin only when glucose is high, slows gastric emptying, and increases satiety.

  • Tirzepatide stimulates both GLP-1 and GIP receptors, giving a double incretin effect — leading to even greater metabolic and weight benefits.

⚖️ 3. Weight Loss Results — and What the Numbers Mean

  • In the STEP trials, semaglutide users lost about 10–15% of body weight over ~1.5 years.

  • In SURMOUNT-1, tirzepatide users lost around 20% at higher doses — results once thought possible only after bariatric surgery.

  • Both drugs improve blood pressure, cholesterol, fatty liver, and glycemic control.

  • Tirzepatide also showed over 90% reduction in diabetes progression among people with prediabetes.

❤️ 4. Heart Benefits

  • Semaglutide (SELECT trial, NEJM 2023): lowered major cardiovascular events in overweight/obese adults without diabetes but with prior heart disease.

  • This was a landmark finding — proving an anti-obesity drug can save lives.

  • Tirzepatide’s CV outcome trial is ongoing (SURPASS-CVOT) — early results suggest at least equal safety compared to other GLP-1 drugs.

🔁 5. The “Rebound Weight Gain” Concern — Let’s Clarify

Yes, weight regain after stopping GLP-1 or tirzepatide is real.

  • In STEP-extension and SURMOUNT-4, people who stopped the drug regained much of the lost weight within months.

  • Those who continued treatment maintained their weight loss.

But this doesn’t mean the drugs “fail.”
It means obesity is a chronic disease, not a short-term problem.
Just like blood pressure rises after stopping antihypertensives, or sugar rises after stopping insulin — the condition returns if treatment stops.

So, doctors aren’t “against” these drugs — they’re just reminding us that:

  • Stopping too soon usually leads to rebound.

  • Long-term or maintenance therapy (with lifestyle support) is needed.

  • We must plan follow-up strategies — nutrition, activity, behavioral support — before starting.

In short:
These drugs don’t cure obesity — they help manage it effectively while used.
With ongoing treatment, patients can sustain major benefits safely.

⚠️ 6. Safety Snapshot

Most side effects are digestive and improve with time:

  • Nausea, vomiting, diarrhea, constipation

  • Gallstones (from rapid weight loss)

  • Rare pancreatitis — stop if severe abdominal pain occurs

  • Kidney injury — from dehydration

  • Avoid if there’s a personal/family history of medullary thyroid cancer or MEN2

  • Stop before pregnancy (especially semaglutide)

Also, beware of unregulated or compounded “GLP-1” products sold online — these can be unsafe.

🩺 7. What to Monitor

Before starting:
✔️ Kidney function, thyroid/family history, pancreatitis risk
✔️ Pregnancy plan discussion
✔️ Adjust insulin or sulfonylureas if used

During therapy:
✔️ Watch for GI side effects, dehydration
✔️ Check weight, BP, HbA1c, lipids
✔️ Counsel on gallbladder and thyroid symptoms

Before stopping:
✔️ Have a maintenance plan — dietitian, exercise, behavior therapy, or alternate meds

🤝 8. The Long Game — Multidisciplinary Care Works Best

Obesity care succeeds when medication is part of a long-term, team-based plan:
🏃‍♀️ Exercise + 🍎 Nutrition + 🧠 Behavioral support + 💊 Pharmacotherapy
Endocrinologists, dietitians, cardiologists, and psychologists together can help patients maintain health and minimize relapse.

📘 9. Updated Guidelines (2024–2025)

  • EASO (Europe, 2025): Recommends semaglutide/tirzepatide as first-line pharmacotherapy for many people with obesity and related complications.

  • ADA (2025): Encourages their use in T2DM when weight loss and heart protection are priorities.

  • NICE (UK): Reviewing cost and access policies through 2025.

💬 10. The Balanced Bottom Line

✅ Benefits:

  • Remarkable and sustained weight loss

  • Strong glycemic control

  • Heart protection (for semaglutide)

  • Huge potential for diabetes prevention

⚠️ Limitations:

  • Weight returns after stopping (unless lifestyle or therapy continues)

  • Cost and access barriers

  • Ongoing monitoring for rare side effects

💡 Doctor’s Perspective

“GLP-1 and GIP/GLP-1 agonists are game-changers — but not magic bullets.
They work beautifully when part of a structured, long-term obesity care plan.
Think of them not as a quick fix, but as a chronic therapy for a chronic disease.”
— Dr. Sk Sabir Rahaman

🧾 Key Studies to Know

  • SELECT Trial (Semaglutide CVOT) — NEJM, 2023

  • SURMOUNT-1 (Tirzepatide for Obesity) — NEJM, 2022

  • Head-to-Head: Tirzepatide vs Semaglutide — NEJM, 2025

  • SURMOUNT-4 (Maintenance Trial) — JAMA, 2024

  • FDA Wegovy/Ozempic Labeling — Access Data, 2025

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