A Deep Dive Into GLP-1 Therapies in 2026: Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES

Over the past decade, glucagon-like peptide 1 (GLP-1) receptor agonists have evolved from niche injectable glucose-lowering agents into foundational therapies for diabetes, obesity, and a broadening spectrum of cardiometabolic conditions. In a discussion with The American Journal of Managed Care^® (AJMC^®), Diana Isaacs, PharmD, BCPS, BC-ADM, CDCES, a clinical pharmacist in endocrinology and director of education and training in diabetes technology at the Cleveland Clinic, described the current moment as “transformative.”

The approval of the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonist tirzepatide in 2022 marked a pivotal inflection point, Isaacs noted. Its potency for both hemoglobin A_1C (HbA_1C) reduction and weight loss rapidly earned it a prominent place in the American Diabetes Association Standards of Care, alongside high-dose semaglutide. Weekly formulations have improved adherence compared with older, more frequent injections, while robust cardiovascular outcome data with dulaglutide, semaglutide, and now tirzepatide have elevated GLP-1–based agents from surrogate-focused therapies to tools for reducing major adverse cardiovascular events, kidney disease progression, and other complications.

Isaacs emphasized that GLP-1 therapies are increasingly being deployed earlier in the disease course, supported by data such as the the phase 4 SURPASS-EARLY (NCT05433584) program with tirzepatide. This aligns with a “treat to target” rather than “treat to fail” philosophy, aiming to push HbA_1C into the normal or near-normal range without hypoglycemia risk and to prevent long-term complications.

Their role now extends into conditions such as metabolic dysfunction–associated steatohepatitis (MASH), sleep apnea, and possibly even substance use disorders, with semaglutide already securing key indications beyond diabetes and obesity. Routine screening for MASH using tools like the FIB-4 score, Isaacs argued, should be part of comprehensive diabetes care.

Access and affordability remain critical. Although prior high prices led to discontinuation and rebound hyperglycemia or weight regain, federal pricing agreements capping Medicare costs around $245 per month and expanding direct-to-patient models are improving access. Isaacs urged payers to consider proactive rather than reactive coverage, given the potential to prevent diabetes, kidney disease, and cardiovascular events.

Looking ahead, triple agonists such as retatrutide, monthly GLP-1 injectables, and combination agents like cagrilintide plus semaglutide may further intensify weight and glucose effects. For health plans and managed care leaders, Isaacs’ message is clear: staying current with this rapidly evolving class is essential, as GLP-1–based therapies continue to redefine standards of care in 2026 and beyond.