Section 1: Introduction -- The Drug Everyone Is Asking About

A 52-year-old woman in Kingston attends her primary care clinic. She has type 2 diabetes, hypertension, and a BMI of 38. She is on metformin, lisinopril, and amlodipine. She has seen social media posts about Ozempic. She has read that it makes people lose weight without trying. She wants to know if she can get it.

Her clinician has three patients that afternoon asking the same question. One has type 2 diabetes. One has obesity but no diabetes. One has neither -- she wants the drug because a celebrity she follows takes it.

GLP-1 receptor agonists -- semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide -- have become the most-discussed class of drugs in popular culture since statins. Their effects on weight are real and significant. Their cardiovascular and renal benefits in patients with type 2 diabetes are well-documented. Their mechanisms are understood. Their adverse effects are manageable but meaningful. And their place in Caribbean clinical practice -- where diabetes prevalence exceeds 12%, obesity is widespread, and access to these drugs is constrained by cost, cold chain, and formulary -- requires careful consideration.

This report provides the clinical evidence, the safety profile, the drug interactions, the Caribbean-specific considerations, and a framework for the conversation every clinician in the region is now having.

Section 2: What GLP-1 Receptor Agonists Actually Do

2.1 The mechanism

GLP-1 (glucagon-like peptide-1) is an incretin hormone produced in the gut in response to eating. It stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon release, slows gastric emptying, and acts on the brain's satiety centres to reduce appetite.

GLP-1 receptor agonists mimic this hormone with a substantially longer half-life -- from hours (exenatide twice daily) to a week (semaglutide once weekly). The result is prolonged insulin stimulation, prolonged appetite suppression, and prolonged gastric slowing.

2.2 The glycaemic effect

All GLP-1 receptor agonists reduce HbA1c, typically by 1.0-1.5 percentage points. They produce glucose-dependent insulin secretion -- meaning they do not cause hypoglycaemia when used as monotherapy or in combination with metformin. Hypoglycaemia risk increases when combined with insulin or sulfonylureas.

2.3 The weight effect

Weight loss is a class effect, mediated primarily through central appetite suppression and delayed gastric emptying. Mean weight loss:

The weight loss with semaglutide 2.4 mg (Wegovy) is substantially greater than any previous pharmacological weight management option and has driven the public attention this class has received.

2.4 The cardiovascular effect

Three GLP-1 receptor agonists have demonstrated cardiovascular mortality benefit in randomised controlled trials in patients with type 2 diabetes and established cardiovascular disease or high cardiovascular risk:

• Liraglutide (LEADER trial, 2016): Reduced major adverse cardiovascular events (MACE) by 13% vs placebo. Reduced cardiovascular death.
• Semaglutide (SUSTAIN-6 trial, 2016): Reduced MACE by 26% vs placebo.
• Semaglutide (SELECT trial, 2023): Reduced MACE in patients with obesity and cardiovascular disease but WITHOUT diabetes -- the first cardiovascular outcomes trial demonstrating benefit of a weight management drug independent of glycaemic control.

2.5 The renal effect

Liraglutide (LEADER) and semaglutide (FLOW trial, 2024) have demonstrated renal protective effects -- reduced progression of diabetic kidney disease, reduced urinary albumin:creatinine ratio. The FLOW trial was specifically designed for patients with type 2 diabetes and CKD and was stopped early due to clear benefit.

Section 3: Who They Are For -- and Who They Are Not For

3.1 Evidence-based indications

3.2 Who they are NOT for

Section 4: The Adverse Effects -- What Patients Need to Know

4.1 Gastrointestinal effects -- the main reason people stop

Nausea, vomiting, diarrhoea, and constipation are the most common adverse effects, occurring in up to 40% of patients during initiation and dose escalation. They are dose-dependent and improve over time in most patients.

Management: Start at the lowest dose and escalate slowly. With semaglutide, the standard escalation is every 4 weeks. Eating smaller, lower-fat meals and avoiding lying down after eating reduces nausea. In patients with existing gastroparesis (including many Caribbean diabetic patients), GLP-1 RA-induced gastric slowing can substantially worsen symptoms.

Clinical implication: GLP-1 receptor agonists slow gastric emptying. This delays the absorption of co-prescribed oral medications. In a patient on warfarin, this can produce INR instability during initiation. In a patient on oral hypoglycaemics, the pharmacokinetics change.

4.2 Pancreatitis

GLP-1 receptor agonists have been associated with acute pancreatitis in post-marketing surveillance, though causality remains contested in the literature. The absolute risk is small but the consequence is serious. Patients should be counselled to seek medical attention for persistent severe abdominal pain.

4.3 Gallbladder disease

Rapid weight loss -- and GLP-1 RA use specifically -- is associated with increased cholelithiasis (gallstone formation). The SCALE trials demonstrated a higher rate of gallbladder-related events with liraglutide vs placebo.

4.4 Thyroid effects

Rodent studies demonstrated dose-dependent thyroid C-cell tumours with GLP-1 receptor agonists. This has not been replicated in human epidemiological data, but all drugs in this class carry a contraindication for patients with personal or family history of medullary thyroid carcinoma or MEN2.

4.5 Muscle loss

In the STEP 1 trial, approximately 39% of weight lost with semaglutide was lean mass (muscle). This proportion is higher than typically observed with lifestyle interventions alone. In Caribbean populations, where sarcopenia in older adults already contributes to functional decline, this is a consideration in older patients pursuing GLP-1-mediated weight loss.

The clinical implication: GLP-1 receptor agonist prescribing for obesity should ideally be accompanied by resistance exercise and adequate protein intake to preserve muscle mass. This is not always practical in Caribbean settings.

4.6 Cardiovascular effects in patients at low risk

The cardiovascular benefit trials enrolled high-risk patients (established CVD or high cardiovascular risk). Extrapolating these benefits to lower-risk patients -- or to patients without diabetes using the drug purely for weight management -- is not supported by the same evidence base.

Section 5: Drug Interactions

5.1 Insulin and sulfonylureas

GLP-1 receptor agonists combined with insulin or sulfonylureas carry a significant hypoglycaemia risk. When initiating a GLP-1 RA in a patient already on insulin or a sulfonylurea: - Reduce the sulfonylurea dose by 50% on initiation - Reduce the insulin dose by 20% on initiation - Counsel the patient on hypoglycaemia recognition and management

5.2 Warfarin and narrow-index drugs

GLP-1 receptor agonists slow gastric emptying, which delays absorption of orally administered drugs. In patients on warfarin, this can produce INR instability -- particularly during dose escalation when the gastric slowing effect is changing. Monitor INR more frequently during GLP-1 RA initiation in patients on warfarin.

For other narrow-index oral drugs (phenytoin, digoxin, ciclosporin), the clinical significance of delayed absorption is uncertain but monitoring is prudent.

5.3 Oral contraceptives

Delayed gastric emptying theoretically reduces the absorption reliability of oral contraceptives. Clinical evidence for this interaction is limited, but patients should be counselled and alternative contraceptive methods considered if compliance with timing is uncertain.

5.4 Orlistat

Orlistat (a lipase inhibitor used for weight management) combined with a GLP-1 receptor agonist produces additive GI adverse effects. The combination is generally not recommended.

Section 6: Caribbean-Specific Considerations

6.1 Access and cost

Semaglutide (Ozempic 1 mg) carries a significant cost. In the United States, the monthly cost without insurance is approximately US$900. Caribbean pricing varies but remains substantially above what is accessible for most patients in public health systems. Formulary inclusion is limited across the Caribbean.

In practice, this means GLP-1 receptor agonist prescribing in the Caribbean is largely confined to private patients with the means to self-fund, or to patients who obtain the drug from informal channels -- including purchasing abroad, using insulin pens of varying provenance, or using compounded semaglutide.

Compounded semaglutide (produced by compounding pharmacies, particularly in the United States) became widely available during the Ozempic shortage of 2022-2024. It is not bioequivalent to the branded product, is not subject to the same manufacturing standards, and has been associated with dosing errors. Clinicians should ask specifically whether patients are obtaining compounded products.

6.2 Cold chain requirements

GLP-1 receptor agonists require refrigeration (2-8 degrees Celsius). In Caribbean territories with unreliable electricity or limited cold chain infrastructure, storage integrity is a genuine concern. Patients transporting drugs from abroad may compromise efficacy through inadequate refrigeration.

6.3 Needle use in injection-naive patients

Weekly subcutaneous injection is a significant barrier for patients who have never self-injected. Training, pen device availability, and needle disposal facilities are all relevant.

6.4 The diabetes-first principle

In Caribbean patients with type 2 diabetes, the evidence for GLP-1 receptor agonists is clearest in patients with established cardiovascular disease or CKD -- groups where the drug has demonstrated mortality and renal benefit beyond glycaemic control. For patients without these comorbidities, the choice between GLP-1 RAs and other antidiabetic agents (metformin, SGLT2 inhibitors) should weigh efficacy, safety, cost, and patient preference.

6.5 Obesity without diabetes

The SELECT trial (2023) demonstrated cardiovascular benefit of semaglutide 2.4 mg in patients with obesity and cardiovascular disease but without diabetes. This expands the evidence base beyond glycaemic control. However, the formulation (2.4 mg Wegovy) is distinct from the diabetes formulation (1 mg Ozempic) and the cost differential is significant.

6.6 The social media question

Caribbean clinicians are encountering patients who have self-diagnosed and self-sourced GLP-1 receptor agonists based on social media content. Key points for this conversation:

• The drugs are effective for their indicated populations
• Weight loss is real but partial -- most patients do not achieve and maintain "ideal" body weight
• Weight regains substantially when the drug is stopped (STEP 1 extension data: two-thirds of weight lost was regained within one year of stopping)
• The drug is not a substitute for dietary and physical activity changes
• For patients without a clinical indication (type 2 diabetes, obesity with comorbidity, high cardiovascular risk), the benefit-risk calculation is different from the evidence base

Section 7: The Clinical Conversation

Patient: "Can I get Ozempic?"

Key questions to answer before prescribing:

1. Does the patient have type 2 diabetes? If yes, what is the current HbA1c and what are they already on?
2. Does the patient have a BMI above 30, or above 27 with a weight-related comorbidity?
3. Does the patient have established cardiovascular disease or high cardiovascular risk?
4. Does the patient have CKD? (GLP-1 RAs are specifically beneficial here)
5. Is there a history of pancreatitis, medullary thyroid carcinoma, or MEN2?
6. Is the patient pregnant or planning pregnancy in the next 2 months?
7. Is the patient on insulin or a sulfonylurea? (Dose reduction required)
8. Is the patient on warfarin? (INR monitoring required during initiation)
9. Can the patient access, afford, and store the drug appropriately?
10. Is the patient prepared for GI side effects during initiation?

If the patient has type 2 diabetes with established CVD or CKD, the evidence supports prescribing. If the patient has obesity with a comorbidity, the evidence supports prescribing where access and cost allow. If neither applies, the conversation should include an honest discussion of what the evidence supports and what it does not.

Section 8: About ElesRx

ElesRx includes GLP-1 receptor agonist entries in the clinical database. When a GLP-1 RA is added to a patient's medication list, the system flags hypoglycaemia risk with concurrent insulin or sulfonylureas, INR monitoring requirements in patients on warfarin, and the contraindication in pregnancy and patients with a history of medullary thyroid carcinoma or MEN2.

The tool is available at elesrx.com. ElesRx is a product of PIPPS Smart Apps, a division of J.C. Epiphany Limited (Jamaica, est. 1998).

Section 9: Methodology and References

9.1 Data sources

GLP-1 receptor agonist data is drawn from the ElesRx clinical database, DailyMed, the European Medicines Agency, Health Canada, and the primary trial publications cited below. This report summarises evidence current to mid-2025.

9.2 Limitations

This is a rapidly evolving field. Trial data for additional GLP-1 receptor agonists (tirzepatide, which acts on both GLP-1 and GIP receptors) and for new formulations (oral semaglutide, Rybelsus) is not covered in full. Caribbean-specific prescribing data is limited.

9.3 Author and conflict of interest disclosure

This report was authored by Juliet Duncan, BPharm, founder of J.C. Epiphany Limited and developer of ElesRx. The author has a commercial interest in ElesRx. This report is published without an access gate as a contribution to Caribbean clinical education. No external funding was received.

9.4 Citation

Duncan J. The GLP-1 Report: Semaglutide, Liraglutide, and the Weight Loss Drug Question in Caribbean Practice. ElesRx Clinical Reports, Report 14. Published 2027 at elesrx.com/reports/glp1-report/. J.C. Epiphany Limited, Jamaica.

References

1. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). N Engl J Med. 2016;375(4):311-322. doi:10.1056/NEJMoa1603827

2. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). N Engl J Med. 2016;375(19):1834-1844. doi:10.1056/NEJMoa1607141

3. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563

4. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347

5. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183