ADA: Lilly bests Novo again, takes GLP-1 pill Foundayo to FDA for diabetes approval

Lilly's Foundayo Outperforms Competitors in Type 2 Diabetes Trials

Eli Lilly's oral GLP-1 drug, Foundayo (orforglipron), demonstrated superior blood sugar control and weight loss compared to competing diabetes drugs, including Novo Nordisk's semaglutide, AstraZeneca's Farxiga, and placebo, across three Phase 3 trials (ACHIEVE-2, ACHIEVE-3, ACHIEVE-5). The trials, presented at the 2026 American Diabetes Association conference, involved patients with inadequate glycemic control on prior treatments. Foundayo's consistent performance has solidified its position in type 2 diabetes, leading Lilly to plan an FDA submission for this indication in the second quarter of this year, following its recent approval for chronic weight management.

• In the ACHIEVE-3 trial, Foundayo at a 9-mg dose achieved a 1.9% reduction in HbA1c at 52 weeks, significantly outperforming 7-mg oral semaglutide which showed a 1.1% reduction. Higher doses of Foundayo (17.2 mg) also demonstrated superior HbA1c reduction (2.2% vs 1.4%) and 73.6% greater weight loss compared to 14 mg oral semaglutide.
• Foundayo also delivered strong results in ACHIEVE-2 and ACHIEVE-5. In ACHIEVE-2, it reduced HbA1c by an average of 1.7% at 40 weeks, compared to 0.8% with AstraZeneca’s Farxiga. In ACHIEVE-5, Foundayo achieved up to a 2.1% average HbA1c drop at 40 weeks, significantly better than the 0.8% drop seen with placebo plus insulin glargine.
• Following these positive Phase 3 outcomes, Eli Lilly plans to submit Foundayo for type 2 diabetes approval to the FDA in the second quarter of this year. Analysts from BMO Capital Markets noted Foundayo's "consistently competitive profile" and see significant opportunity for the once-daily oral treatment in the broader T2D therapeutic landscape, building on its recent approval for chronic weight management.

Foundayo's ACHIEVE Program: Efficacy and Safety Outcomes in T2D

Recent clinical investigations have demonstrated significant advances in type 2 diabetes management across multiple therapeutic modalities. The studies encompass novel weekly insulin formulations, combination therapies, and real-world effectiveness analyses spanning 2025-2026.

Foundayo's Competitive Edge in the Oral T2D Landscape

Recent evidence demonstrates that investigational therapies generally provide incremental benefits over standard-of-care treatments, though often with trade-offs in safety or tolerability profiles. The most recent 2026 network meta-analysis of botanical drug combinations showed that Huanglian Jiedu Decoction (HLJDD) combined with metformin achieved superior fasting plasma glucose reduction (MD = -1.46, 95% CrIs=(-2.24, -0.68)) compared to metformin alone across 40 RCTs involving 3,088 patients. Similarly, TMX-049, a novel xanthine oxidoreductase inhibitor, demonstrated a 35% reduction in urinary albumin-to-creatinine ratio versus placebo in diabetic kidney disease patients, though two patients developed gout at the 200 mg dose.

Complex insulin regimens consistently outperform basal insulin alone in glycemic control, with network meta-analysis data from 58 RCTs showing HbA1c improvements of -0.31% for basal-bolus, -0.24% for biphasic, and -0.38% for prandial insulin regimens. However, these benefits come with approximately 1 kg greater weight gain and borderline increased risk of severe hypoglycemia. Conversely, treatment simplification strategies using GLP-1 receptor agonists or SGLT-2 inhibitors as alternatives to bolus insulin achieved equivalent or superior glycemic control while reducing injection frequency, insulin doses, and hypoglycemia risk.

The most compelling evidence for investigational approaches comes from intensive multifactorial interventions, exemplified by the landmark Steno-2 study, which demonstrated substantial risk reductions across multiple endpoints: 53% reduction in cardiovascular events (HR 0.47, 95% CI 0.24-0.73), 61% reduction in nephropathy, 58% reduction in retinopathy, and 63% reduction in autonomic neuropathy. This suggests that comprehensive investigational treatment paradigms targeting multiple pathways simultaneously may offer the greatest therapeutic advantage over conventional standard-of-care approaches, despite requiring more complex management protocols.

Addressing Unmet Needs in Type 2 Diabetes Management

Recent evidence from 2022-2024 reveals significant gaps in type 2 diabetes care that persist despite therapeutic advances. These unmet needs span from fundamental awareness and control issues to specialized population management challenges. The COVID-19 pandemic has further exacerbated existing disparities and created new barriers to optimal diabetes care.

• Persistently low awareness, treatment, and control rates across multiple healthcare systems, with only 56.13% of patients aware of their condition in Southeast China, 47.96% receiving treatment, and merely 18.29% achieving blood glucose control, while South Korea maintained diabetes control rates at just 29.14% from 2020-2022

• Vulnerable demographic populations requiring targeted interventions, including older adults with lower educational levels who show less improvement in awareness and control trends, younger patients (ages 30-44) with higher unmet healthcare needs (OR 1.93 for T2DM), females with elevated risk of unmet needs (OR 1.46), and single-person households with increased risk (OR 1.89)

• Socioeconomic and geographic disparities affecting diabetes management, with low-family income, low-education level, and lack of medical insurance associated with higher T2DM prevalence, while rural populations require widespread screening programs and urban localities show higher diabetes prevalence rates

• COVID-19 pandemic impact creating new healthcare access challenges, with unmet healthcare needs initially declining at pandemic onset but subsequently reversing into statistically significant increasing trends (β 0.527 for T2DM), highlighting the vulnerability of diabetes care during health system disruptions

• Special population management gaps including patients with Alzheimer's disease who are less likely to initiate antidiabetic therapy (particularly newer agents like GLP-1 receptor agonists and SGLT2 inhibitors), hemodialysis patients with 56.6% experiencing hypoglycemic episodes and 30% increased odds of hypoglycemia per additional HD year, and early-onset diabetes patients facing decades of disease management

• Treatment optimization needs for older adults requiring deprescribing strategies, medication burden reduction, and therapeutic realignment rather than additional medications, with major clinical practice gaps in understanding when and how to modify therapy for patients not responding to current regimens