A clinical overview of how GLP-1 and GIP receptor agonists work, who they are suitable for, and why medical supervision is non-negotiable.
In the last three years, GLP-1 receptor agonists have shifted from niche diabetes medications to the most discussed pharmacological interventions in weight management. Semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) are now household names. But the popular conversation around these medications often misses the clinical nuance that determines who benefits, who doesn’t, and how to use them safely.
What Are GLP-1 Medications and How Do They Work?
GLP-1 stands for glucagon-like peptide-1, a hormone naturally produced in the gut in response to food. It performs three critical functions: it stimulates insulin release, suppresses glucagon (which raises blood sugar), and crucially for weight management, it acts on the hypothalamus to reduce appetite and slow gastric emptying.
Semaglutide is a GLP-1 receptor agonist: it mimics this hormone at the receptor level. Tirzepatide (Mounjaro) is a dual agonist, acting on both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. This dual mechanism is thought to explain tirzepatide’s superior weight loss outcomes in the SURMOUNT trial series, where patients achieved an average of 20-22% body weight reduction over 72 weeks.
Mounjaro vs Ozempic: Is One Better?
Clinically, tirzepatide has demonstrated greater mean weight loss in head-to-head comparison data, likely due to the additive GIP receptor action. However, ‘better’ is never a universal answer in medicine. Individual response varies considerably based on receptor sensitivity, baseline metabolic function, comorbidities, and tolerance of side effects.
Approximately 10-15% of patients are ‘non-responders’ to GLP-1 medications. This is often due to underlying hormonal dysregulation, gut microbiome composition, or genetic receptor variants, not lack of adherence. Identifying this early through proper diagnostic assessment prevents wasted time and cost.
Common Side Effects and How to Manage Them
Gastrointestinal side effects (nausea, vomiting, constipation, and diarrhoea) are the most common reasons patients discontinue treatment. These are dose-dependent and largely manageable through careful titration. At our clinic, we use a slower-than-standard titration protocol where clinically appropriate, which significantly reduces early dropout.
- Nausea: Most common in the first 4-8 weeks; managed with dietary modification and slower titration
- Constipation: Requires proactive fibre and hydration advice from the outset
- Fatigue: Often temporary; may indicate inadequate caloric or protein intake
- Muscle loss (sarcopenia): A serious concern with rapid weight loss, mitigated by resistance training and adequate protein prescription
- Pancreatitis: Rare but important; contraindicated in patients with personal or family history
Why Medical Supervision Is Not Optional
The proliferation of online prescribing services has made GLP-1 medications far more accessible, but accessibility is not the same as safety. Appropriate prescribing requires a thorough cardiovascular, endocrine, and renal assessment. Patients with a history of medullary thyroid carcinoma, pancreatitis, severe gastroparesis, or specific cardiac arrhythmias should not be prescribed these medications.
Beyond safety, optimising outcomes requires ongoing clinical monitoring: body composition analysis (to protect muscle mass), nutritional guidance, dosage adjustment, and managing the psychological dimensions of appetite suppression. Weight regain is almost universal upon discontinuation without concurrent behavioural and metabolic work. This is something our programme addresses from the outset.
At Harley Weight Loss Clinic, GLP-1 therapy is prescribed only after a comprehensive diagnostic consultation with Dr Ajaz. It forms one component of a personalised protocol, never a standalone solution.
Written by Dr Saima Ajaz, MBBS, MRCGP
Lead Clinician, Medical Director, Harley Weight Loss Clinic
