ADA 2026: Key Pharmacotherapy Advances in Type 1 and Type 2 Diabetes

The 86th American Diabetes Association (ADA) Scientific Sessions, held June 5 through 8, 2026, in New Orleans, Louisiana, highlighted important advances across the diabetes treatment landscape. While obesity therapeutics and diabetes technology generated considerable attention, several presentations focused specifically on therapies for type 1 diabetes (T1D) and type 2 diabetes (T2D).

Key themes included the emergence of investigational oral incretin therapies, continued development of once-weekly insulin formulations, expanding evidence supporting established therapies such as semaglutide and tirzepatide, and growing momentum behind disease-modifying and regenerative approaches for T1D.

Orforglipron: Oral GLP-1 Therapy Continues to Advance

One of the most anticipated presentations at ADA 2026 involved orforglipron, Lilly's investigational oral nonpeptide glucagon-like peptide (GLP)-1 receptor agonist. Although not FDA approved for T2D at the time of presentation, results from the phase 3 ACHIEVE clinical development program suggest that orforglipron (Foundayo; Eli Lilly) may become an important future treatment option.

In ACHIEVE-5 (NCT06109311), investigators evaluated orforglipron added to titrated insulin glargine in adults with longstanding T2D inadequately controlled on basal insulin. Among 546 participants with a mean diabetes duration of about 15 years and baseline A_1C of 8.5%, all evaluated doses were superior to placebo. Mean A_1C reductions ranged from approximately 1.54% to 2.05% compared with 0.77% for placebo, while body weight decreased by 2.7% to 6.1% versus a 0.6% increase with placebo. Rates of level 2 hypoglycemia were similar between treatment groups despite background insulin therapy.¹

Additional phase 3 data from ACHIEVE-2 (NCT06192108) demonstrated superiority of all evaluated doses of orforglipron compared with dapagliflozin (Farxiga; AstraZeneca) in adults inadequately controlled on metformin. Orforglipron 12 mg and 36 mg produced greater weight loss, whereas the 36 mg dose also resulted in larger reductions in triglycerides, non–high-density lipoprotein cholesterol, and systolic blood pressure.²

Bottom line for pharmacists: Orforglipron remains investigational, but the ACHIEVE program demonstrated clinically meaningful improvements in glycemic control and body weight that could position it as an important future alternative to injectable GLP-1 receptor agonists if approved.

Tirzepatide Continues to Expand Beyond Glycemic Control

Several ADA 2026 presentations reinforced the expanding evidence base for tirzepatide.

The SURPASS-CVOT retinopathy substudy evaluated retinal outcomes among patients with longstanding T2D, established cardiovascular disease, and existing or high-risk diabetic retinopathy. Although tirzepatide (Mounjaro; Eli Lilly) produced substantially greater A_1C reductions than dulaglutide (Trulicity; Eli Lilly) at 6 months (–2.18% vs –1.28%), investigators found no meaningful differences in diabetic retinopathy progression between treatment groups over 12 months. These findings provide reassurance regarding retinal safety despite substantial glucose lowering.³

Another noteworthy oral presentation evaluated major adverse limb events in patients with T2D and peripheral artery disease. In a real-world analysis of more than 24,000 propensity-matched patients, tirzepatide was associated with an approximately 45% lower risk of major adverse limb events compared with injectable semaglutide (Ozempic, Wegovy; RR, 0.55; 95% CI 0.46-0.65). Significant reductions were also observed for critical limb ischemia, amputation, and peripheral revascularization procedures.⁴

Bottom line for pharmacists: Tirzepatide continues to demonstrate benefits extending beyond glucose lowering and weight reduction, with emerging evidence supporting potential vascular and limb-related benefits in high-risk populations.

Semaglutide Remains a Foundational Cardiometabolic Therapy

Although semaglutide is firmly established in diabetes care, ADA 2026 reinforced its expanding role across the cardiometabolic disease spectrum.

One notable oral presentation explored potential mechanisms underlying the cardiovascular benefits observed in the SELECT (NCT03574597) trial. Investigators evaluated 6 proteins previously identified as being modulated by semaglutide and found that changes in several markers—including thrombospondin-2, NT-proBNP, angiopoietin-2, and CD93—appeared to mediate a substantial proportion of semaglutide's reduction in major adverse cardiovascular events. These findings suggest that semaglutide's cardiovascular benefits extend beyond weight loss alone.⁵

Semaglutide also remains the benchmark against which many emerging therapies are compared. Both tirzepatide and investigational agents such as orforglipron and retatrutide (Eli Lilly) are frequently evaluated relative to semaglutide because of its established efficacy, cardiovascular outcomes data, and extensive clinical experience.

In addition, semaglutide remains a component of emerging combination strategies, including IcoSema (Novo Nordisk), the investigational fixed-ratio combination of insulin icodec and semaglutide discussed at ADA 2026.⁶

Bottom line for pharmacists: While newer therapies continue to generate excitement, semaglutide remains one of the most important foundational therapies in diabetes and cardiometabolic care and continues to serve as a key benchmark for emerging therapies.

Retatrutide Remains an Important Investigational Therapy to Watch

Retatrutide, Lilly's investigational triple agonist targeting glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors, continued to generate significant interest throughout ADA 2026 discussions.

Although most of the attention surrounding retatrutide focused on obesity and weight management rather than dedicated diabetes presentations, the therapy remains highly relevant to diabetes care because of its substantial effects on body weight, insulin sensitivity, and glycemic control observed across its development program.

Bottom line for pharmacists: Retatrutide remains investigational, but its potential to address obesity, diabetes, and broader cardiometabolic disease simultaneously makes it one of the most important metabolic therapies currently in development.

Once-Weekly Insulin Moves Closer to Clinical Practice

Insulin innovation remained a major theme at ADA 2026.

Efsitora alfa (Eli Lilly), an investigational once-weekly basal insulin, was evaluated in multiple analyses from the QWINT clinical trial program. A pooled analysis of the QWINT-1 (NCT05662332), QWINT-2 (NCT05362058), QWINT-3 (NCT05275400), and QWINT-4 (NCT05462756) clinical trials demonstrated similar hospitalization rates, length of stay, and hypoglycemia outcomes compared with daily basal insulin comparators including insulin glargine and insulin degludec.⁷

A separate analysis evaluated medication errors across the QWINT clinical trials. Medication errors remained uncommon, occurring in only 1.3% of participants receiving efsitora alfa. Most errors were investigator-related, and the majority of participants experiencing an error completed treatment successfully with comparable glycemic outcomes.⁸

Additional data involving insulin icodec and IcoSema highlighted continued progress toward simplified once-weekly insulin strategies. A network meta-analysis comparing insulin glargine U-300 and insulin icodec demonstrated broadly similar glycemic outcomes, although glargine U-300 was associated with lower rates of level 1 and level 2 hypoglycemia.⁹

IcoSema, the investigational once-weekly combination of insulin icodec and semaglutide, continues to demonstrate promise as a strategy that combines basal insulin and GLP-1 receptor agonist therapy into a single-weekly injection.

Bottom line for pharmacists: Investigational once-weekly insulin formulations, including efsitora alfa, insulin icodec, and IcoSema, continue to demonstrate promising efficacy and safety. If approved, these therapies may reduce treatment burden and improve adherence while simplifying insulin therapy for many patients.

Disease Modification in Type 1 Diabetes Continues to Advance

One of the most exciting themes at ADA 2026 was the continued shift from glucose management toward disease modification in T1D.

The TEPLI-REAL (NCT06892002) study provided real-world evidence supporting implementation of teplizumab (Tzield; Sanofi), currently the only FDA-approved therapy shown to delay progression to stage 3 T1D. The study evaluated outcomes among individuals treated in routine clinical practice and provided important insights regarding treatment implementation beyond the controlled clinical trial setting.

The growing emphasis on T1D screening was also evident throughout the meeting. Earlier identification of at-risk individuals creates opportunities for intervention before symptomatic disease develops and may increase the impact of disease-modifying therapies, such as teplizumab.

Bottom line for pharmacists: Teplizumab remains the only FDA-approved therapy shown to delay progression to stage 3 T1D. ADA 2026 highlighted continued momentum toward earlier identification of at-risk individuals and broader implementation of disease-modifying therapies.

Advances in Beta-Cell Replacement and Regenerative Medicine

Several presentations highlighted investigational approaches aimed at preserving, restoring, or replacing endogenous insulin production.

SAB-142 (SAB Biotherapeutics), an investigational fully human multispecific antithymocyte globulin, demonstrated favorable safety, pharmacokinetic, immunogenicity, and pharmacodynamic findings in individuals with new-onset T1D. These data support continued development of immune-directed therapies designed to preserve residual β-cell function.¹⁰

Investigators also presented data on N-104, a next-generation dual-action immunoregulatory and regenerative therapy. In preclinical studies, N-104 improved β-cell survival, enhanced insulin secretion, and delayed disease progression, supporting the concept that future therapies may combine immune modulation with β-cell regeneration.¹¹

Beyond immunomodulatory therapies, ADA 2026 featured multiple presentations focused on stem cell-derived beta-cell replacement, immune-evasive cellular engineering, and strategies designed to improve graft survival following transplantation. Collectively, these presentations demonstrated continued progress toward therapies capable of restoring endogenous insulin production rather than simply replacing insulin.

Bottom line for pharmacists: Regenerative medicine remains one of the most exciting areas of diabetes research. Although these therapies remain investigational, ADA 2026 highlighted meaningful advances toward therapies that may ultimately preserve or restore beta-cell function and alter the natural history of T1D.

Looking Ahead

ADA 2026 highlighted a future in which diabetes management extends well beyond glucose lowering alone. Presentations reinforced the expanding role of incretin-based therapies, the promise of investigational oral GLP-1 receptor agonists and once-weekly insulin formulations, and growing momentum toward disease modification and beta-cell preservation in T1D.

While many of the therapies discussed remain investigational, the findings presented at ADA 2026 provide insight into the next generation of diabetes care and underscore the important role pharmacists will play in translating these advances into clinical practice.

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