Anne Komé, PharmD, Discusses Key Metabolic Drug Effects Emerging Postapproval

The sodium-glucose cotransporter-2 (SGLT-2) inhibitors' role in promoting ketogenesis and the glucagon-like peptide-1 (GLP-1) receptor agonists' effects on gastric emptying were both characterized largely in the postmarketing setting, raising questions about how thoroughly the metabolic profiles of novel agents are understood before patients receive them. The topic was taken up at the American Diabetes Association 2026 Scientific Sessions, examining how postapproval science is reshaping our understanding of these drug classes.

Anne Komé, PharmD, CPP, BCACP, CDCES, a clinical pharmacist practitioner in the Endocrinology Clinic at the UNC Chapel Hill Medical Center, and moderator of the session “Perturb & Observe: What Pharmacologic Challenges Reveal about Human Metabolism,” tied the current landscape to a pivotal regulatory inflection point.

"Historically, in 2008, the FDA started to require cardiovascular outcomes trials for type 2 diabetes—and then since then, that's kind of how we've learned about all these other benefits," she said, noting that the mandate effectively created an inadvertent mechanism for uncovering secondary effects.

Komé expressed optimism that the field is shifting away from sequential discovery. Pharmaceutical companies, she said, are increasingly evaluating metabolic effects concurrently during development rather than waiting for postmarketing indications to emerge. She cited ongoing work at Amgen on a once-monthly GLP-1 agent, with simultaneous trials underway for obstructive sleep apnea, cardiovascular disease, diabetes, and obesity.

That concurrent approach matters in practice—because how a clinician selects among GLP-1 agents today already depends heavily on the mechanism and indication. "I have to look at the patient in front of me and say, 'Am I doing this for glycemic control versus am I doing this for obesity?’" she explained. Potency, lean muscle mass risk, cardiovascular or renal labeling, and comorbidity burden all factor into individualized selection.

The message from the session: earlier, broader mechanistic study isn't just scientifically valuable; it's increasingly essential to responsible prescribing.