GLP-1 Agonists: Making the Informed Choice

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Curious about the science behind today’s most talked-about diabetes and weight-management treatments? Our new, four-part blog series on GLP-1 Agonists will break down everything you need to know — from how these drugs work, to their real-world results, side effects, and what’s coming next in the pipeline.

Today, we’re covering how someone might choose between GLP-1 molecules, using a goal-based approach. We’ll also go over typical dosing, and risks to watch out for when starting on this class of drugs for the first time.

Below are some factors that influence which GLP-1 agonist might be the best choice depending on the situation and goals of the person considering their use:

Primary Goal

If the main goal is blood sugar / HbA1c reduction (e.g. in T2DM), many of the drugs listed above are viable.

If weight loss / obesity is a major goal, drugs with obesity-indications (Wegovy, Zepbound, Saxenda) or higher-doses of semaglutide/liraglutide may be preferable.

Cardiovascular & Renal Benefits

Some GLP-1s have shown strong evidence of reducing cardiovascular events (myocardial infarction, stroke) in people with T2DM + cardiovascular disease (see liraglutide, semaglutide injectable, dulaglutide).

Also, kidney-protective effects have been demonstrated by many GLP-1 class molecules.

Convenience & Route of Administration

Route of administration depends heavily on personal preference. GLP-1s can be taken via weekly injections, daily injections or via oral formulations.

Some people prefer fewer injections; others may prefer daily for more “granular” control or dose titration.

Oral semaglutide (Rybelsus) offers a non-injection route, but requires special timing due to bioavailability (empty stomach, etc.).

Side Effect Profiles & Tolerability

Gastrointestinal side effects (nausea, vomiting, diarrhea, constipation) are common, especially when initiating or increasing dose.

There is some risk of pancreatitis (rare), gallbladder disease, possible effects on thyroid C-cells (in animal studies) in some cases.

The speed of dose escalation matters for tolerability.

Cost, Insurance Coverage & Access

Due to demand, manufacturing supply and recency of discovery, these drugs tend to be expensive. Insurance may only cover certain brand-names or only if certain criteria are met (BMI thresholds, comorbidities, etc.).

In Canada, Health Canada approvals exist, but reimbursement / public formulary status varies.

Supply issues have been present but are stabilizing in many regions.

Patient Characteristics / Comorbidities

Kidney or liver disease, history of pancreatitis, risk of medullary thyroid carcinoma, pregnancy, may all affect safety on a case-by-case basis.

Age could also affect which drug may be right for you (pediatric/adolescent approvals differ).

Typical Dosing & Titration

People prescribed GLP-1s typically start at a lower “starter dose” to improve tolerability (especially GI side effects). The dose is then gradually increased (weekly or after a few weeks) until reaching a maintenance dose that balances efficacy & side effects.

As an example, semaglutide injectable for diabetes might begin low, then increase in steps to full dose; obesity doses are higher.

Oral semaglutide (Rybelsus) has special guidelines: it is usually taken with a small amount of water after overnight fast; wait before eating or taking other medications.

Risks, Side Effects & Monitoring

Some common side effects may include nausea, vomiting, diarrhea or constipation; decreased appetite; possibly mild hypoglycemia when used with other glucose-lowering drugs.

Some less common but more serious risks are pancreatitis; gallbladder disease; dehydration; kidney effects (if volume depletion); possible risk to pancreatic islets; possible risk to thyroid (shown in animal studies) in some agents.

You may be at higher personal risk of serious side effects if you have a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2; have severe gastrointestinal disease; are pregnant; have other certain pancreatitis risks.

In Part 3, we’ll be looking at what new GLP-1 molecules are coming down the development pipeline, and what’s next for this class of “miracle drugs.” It’s releasing exclusively on our blog November 11th, so make sure to add us to your bookmarks to stay up to date!: https://joinastudy.ca/canadian-health-blog/

Sources

https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists

https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/health-product-infowatch/december-2024.html

https://pubmed.ncbi.nlm.nih.gov/26371721/

https://www.endocrinologyadvisor.com/ddi/glp-1-agonists/

https://hopkinsdiabetesinfo.org/medications-for-type-2-diabetes-glp-1-agonists/

https://www.ncbi.nlm.nih.gov/books/NBK551568/

https://www.ncbi.nlm.nih.gov/books/n/rc72848269830370/

https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-shortages/information-consumers/supply-notices/ozempic.html

https://www.practicenursing.com/content/clinical/glp-1-receptor-agonists-and-their-role-in-managing-type-2-diabetes

https://www.drugs.com/medical-answers/glp-1-drug-best-weight-loss-3579236/

https://www.primetherapeutics.com/en/glp-1-pipeline-update-november-2024