GLP-1 Agonists: Looking to the Future

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Following the success of Ozempic®, Wegovy®, and other GLP-1 receptor agonists, pharmaceutical companies are racing to develop the next wave of metabolic drugs. These new therapies build on the proven benefits of currently approved GLP-1s—lowering blood sugar, supporting weight loss, and reducing cardiovascular risk—while aiming for even greater results in weight management and metabolic health.

The table below highlights some of the most promising GLP-1 drugs and multi-agonist combinations currently in clinical development, the companies behind them, and the additional health conditions they’re being studied for. From oral GLP-1s to triple-action molecules targeting obesity, fatty liver disease, and cardiovascular outcomes, these next-generation treatments could reshape the future of diabetes and obesity care.

Drug Candidate	Company / Sponsor	Mechanism / Targets	Indications Being Tested	Clinical Phase & Highlights
Orforglipron	Eli Lilly and Company	Oral, small‐molecule GLP-1 receptor agonist	Type 2 diabetes; Obesity/weight-management	Phase 3: in the ACHIEVE-1 trial (T2D) showed ~1.3–1.6 % HbA1c reduction at 40 weeks, and ~7.9 % body-weight loss in highest dose arm.
Retatrutide (LY-3437943)	Eli Lilly	Triple agonist: GLP-1 + GIP + Glucagon receptors	Obesity; Type 2 diabetes; Fatty liver disease (MASLD/NASH)	Phase 2/3: In a 48-week obesity study, doses 8 mg & 12 mg achieved ~22.8-24.2 % weight loss; in a liver-fat substudy in MASLD, >80 % reduction in liver fat at 24-48 weeks.
CagriSema (combination semaglutide + cagrilintide)	Novo Nordisk	Dual agonist: GLP-1 + Amylin analog (cagrilintide)	Obesity / weight management; Metabolic disease	Under development (late-stage) — aims to enhance weight-loss efficacy beyond standalone GLP-1.
Amycretin	Novo Nordisk	Dual agonist: GLP-1 + Amylin (experimental)	Obesity; Metabolic disorders	Early to mid‐stage trials.
Survodutide	Zealand Pharma (with Boehringer Ingelheim)	GLP-1 + Glucagon receptor co-agonist	Obesity; Non-alcoholic steatohepatitis (NASH)	In development — exploring metabolic/ liver-disease indications.
Danuglipron	Pfizer	Once-daily oral GLP-1 receptor agonist	Obesity / weight loss	Development terminated Apr-2025 due to a liver-injury safety signal.

These drugs reflect major shifts: from injectable only to oral formulations (e.g., Orforglipron); and from single-target (GLP-1) to multi-agonist (GLP-1 + GIP, GLP-1 + Glucagon, GLP-1 + Amylin) aiming for stronger weight-loss and broader metabolic effects. Their indication expansion is broadening: beyond T2DM and obesity to include MASLD/NASH, cardiovascular disease, kidney disease, and fatty-liver/steatosis. For example, Retatrutide showed marked liver-fat reduction in a MASLD subgroup.

An additional note for Orforglipron: Eli Lilly expects regulatory filings toward late-2025 (obesity) and possibly 2026 (diabetes) based on clinical results.

As we can see from the final drug listed in the table above, not all testing pipelines result in success: Danuglipron’s termination underscores that safety (e.g., liver injury) and tolerability remain critical obstacles to the approval of new GLP-1s.

These developments have implications for future treatment paradigms: improved convenience (oral), wider access global scale, more powerful weight-loss, and potentially new classes of metabolic disease therapies.

In Part 4, we’ll review some of the most Frequently Asked Questions regarding GLP-1s, and their answers. It’s releasing exclusively on our blog November 14th, so make sure to add us to your bookmarks to stay up to date!: https://joinastudy.ca/canadian-health-blog/

Sources

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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/

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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

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