ADA 2026: Lipid Management and Cardiovascular Prevention Updates for People With Diabetes

Cardiovascular disease remains the leading cause of morbidity and mortality among people with diabetes. Although advances in glucose-lowering therapies have transformed diabetes management, residual cardiovascular risk remains substantial. At the 86th American Diabetes Association (ADA) Scientific Sessions, several important presentations focused on lipid management and cardiovascular prevention, highlighting both persistent treatment gaps and emerging therapies that may help further reduce cardiovascular risk.

Among the most impactful presentations were new data from the VESALIUS program evaluating evolocumab (Repatha; Amgen) in high-risk primary prevention populations, emerging evidence supporting oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with enlicitide, and real-world analyses evaluating bempedoic acid (Nexletol; Esperion Therapeutics). Together, these findings reinforce the importance of earlier and more aggressive lipid management in people with diabetes.

VESALIUS-REAL Highlights a Major Treatment Gap

One of the most striking findings presented at ADA 2026 came from the VESALIUS-REAL Global Study, which evaluated lipid management patterns among 354,643 patients with high-risk diabetes across North America, Europe, and Asia-Pacific.¹

Despite guideline recommendations emphasizing aggressive lipid management in high-risk patients, fewer than half of participants (46%) were receiving lipid-lowering therapy at baseline. Among patients not receiving treatment, only 26% initiated therapy within 1 year. Even among those already receiving lipid-lowering therapy, only 7% underwent treatment intensification during follow-up. Low-density lipoprotein cholesterol (LDL-C) monitoring was also suboptimal, with only 42% undergoing LDL-C testing within 1 year. Most concerning was only 22% achieved guideline-recommended LDL-C targets.¹

These findings underscore a significant global gap between guideline recommendations and real-world clinical practice.

Bottom line for pharmacists: Many high-risk patients with diabetes remain untreated, undertreated, or inadequately monitored. Pharmacists are uniquely positioned to identify treatment gaps, recommend therapy intensification, and improve achievement of LDL-C targets.

VESALIUS-CV Expands the Role of PCSK9 Inhibition in Primary Prevention

The importance of closing these treatment gaps was reinforced by results from VESALIUS-CV (NCT03872401), a landmark cardiovascular outcomes trial evaluating evolocumab in patients at high cardiovascular risk without a prior myocardial infarction or stroke.²

Among 12,257 participants enrolled in VESALIUS-CV, nearly half (6,002 patients) had high-risk diabetes. After a median follow-up of about 4.6 years, evolocumab reduced 3-point major adverse cardiovascular events (MACEs) by approximately 29% compared with placebo in patients with high-risk diabetes. Evolocumab also reduced 4-point MACEs by 21% and lowered myocardial infarction risk by 35%.²

Importantly, benefits were observed regardless of baseline LDL-C, statin intensity, use of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide (GLP)-1 receptor agonists, and even among patients without established atherosclerotic cardiovascular disease (ASCVD).²

Historically, PCSK9 inhibitors have primarily been viewed as secondary prevention therapies. VESALIUS-CV challenges that paradigm and suggests that selected high-risk patients with diabetes may benefit from intensive LDL-C lowering before experiencing a first cardiovascular event.

Bottom line for pharmacists: VESALIUS-CV supports earlier cardiovascular risk reduction and demonstrates that intensive LDL-C lowering with evolocumab can prevent first cardiovascular events in appropriately selected high-risk patients with diabetes.

Oral PCSK9 Inhibition Moves Closer to Reality

One of the most exciting lipid management developments presented at ADA 2026 involved enlicitide (Merck), an investigational oral PCSK9 inhibitor.

Although currently available PCSK9 inhibitors require subcutaneous administration, enlicitide offers the possibility of oral LDL-C lowering through PCSK9 inhibition. Data presented at ADA 2026 demonstrated robust LDL-C reductions among participants with and without diabetes. Importantly, rates of worsening diabetes were similar between enlicitide and placebo (9.3% vs 8.8%), and there were no clinically meaningful differences in hemoglobin A_1C were observed over time, supporting the glycemic neutrality of oral PCSK9 inhibition.³

For clinicians managing patients who require additional LDL-C lowering but are hesitant to initiate injectable therapy, oral PCSK9 inhibition could represent an important future treatment option.

Bottom line for pharmacists: Enlicitide may eventually expand access to intensive LDL-C lowering by providing an oral alternative to injectable PCSK9 inhibitors without adversely affecting glycemic control.

Bempedoic Acid Continues to Build Evidence

Several lipid-focused abstracts evaluated bempedoic acid, an ATP citrate lyase inhibitor increasingly used in patients requiring additional LDL-C reduction.

Particularly noteworthy was a real-world analysis comparing cardiovascular outcomes among adults with T2D receiving bempedoic acid versus ezetimibe (Zetia; Organon) in addition to moderate-intensity statin therapy.⁴

The propensity-matched analysis included 2,990 patients with T2D. Bempedoic acid was associated with a 35% lower risk of a composite endpoint consisting of stroke, myocardial infarction, or new-onset heart failure compared with ezetimibe (relative risk, 0.65 [95% CI, 0.52-0.82]; P < .001).⁴

Interestingly, LDL-C reduction was numerically greater with ezetimibe than with bempedoic acid. These findings suggest that mechanisms beyond absolute LDL-C lowering may contribute to the cardiovascular benefits observed with bempedoic acid.⁴

Bottom line for pharmacists: Bempedoic acid continues to emerge as an important nonstatin therapy and may provide cardiovascular benefits beyond solely lowering LDL-C.

Additional Lipid Findings

Another noteworthy presentation evaluated the association between PCSK9 inhibitor use and incident diabetes risk in a large global real-world analysis.⁵ Using TriNetX data, investigators compared more than 20,000 propensity-matched patient pairs receiving PCSK9 inhibitors with patients receiving statins, ezetimibe, or fenofibrate. PCSK9 inhibitor therapy was associated with a significantly lower risk of incident diabetes across all comparator groups.⁵

Although additional studies are needed to confirm these findings, the results provide further reassurance regarding the metabolic safety of intensive LDL-C lowering strategies and may help address concerns regarding diabetes risk when pursuing aggressive lipid management.

What Pharmacists Should Take Away from ADA 2026

Several themes emerged consistently throughout the cardiovascular prevention sessions at ADA 2026^1-4:

• High-risk patients remain undertreated. VESALIUS-REAL demonstrated substantial gaps in lipid monitoring, treatment initiation, treatment intensification, and LDL-C goal attainment.¹
• Earlier intervention matters. VESALIUS-CV showed that aggressive LDL-C lowering can reduce first cardiovascular events in high-risk patients with diabetes before ASCVD develops.²
• The lipid toolbox continues to expand. Emerging therapies—such as oral PCSK9 inhibitors—may provide additional options for patients unable or unwilling to use injectable therapies.³
• Nonstatin therapies are increasingly important. Data involving evolocumab, enlicitide, and bempedoic acid reinforce the growing role of nonstatin therapies in comprehensive cardiovascular risk reduction.^2-4

Looking Ahead

ADA 2026 highlighted continued progress toward more aggressive and individualized cardiovascular risk reduction in people with diabetes. Emerging evidence from VESALIUS-CV, VESALIUS-REAL, enlicitide, and bempedoic acid studies suggests that the future of lipid management will involve earlier intervention, expanded therapeutic options, and greater emphasis on preventing the first cardiovascular event rather than simply responding after one occurs.

For pharmacists, identifying high-risk patients, optimizing lipid-lowering therapy, addressing therapeutic inertia, and helping patients achieve evidence-based LDL-C targets remain critical opportunities to improve cardiovascular outcomes.

REFERENCES

1. Chan Q, Sakhuja S, Budoff M, et al. Lipid management in patients with high-risk diabetes mellitus at risk for a first major atherosclerotic cardiovascular event: findings from the VESALIUS-REAL global study. Diabetes. 2026;75(Suppl 1):1448-P. doi:10.2337/db26-1448-P

2. Leiter L, Marston N, De Ferrari GM, et al. Evolocumab reduces cardiovascular events in patients with high-risk diabetes: results from the VESALIUS-CV trial. Diabetes. 2026;75(Suppl 1):1247-OR. doi:10.2337/db26-1247-OR

3. Parham J, Blom DJ, Leiter LA, et al. Efficacy and safety of enlicitide, an oral PCSK9 inhibitor, in participants with and without diabetes mellitus in a pooled analysis of two phase 3 trials. Diabetes. 2026;75(Suppl 1):1246-OR. doi:10.2337/db26-1246-OR

4. Ansong B, White R, Cowart K, et al. Association of cardiovascular outcomes with bempedoic acid versus ezetimibe added to moderate-intensity statin therapy in people with type 2 diabetes. Diabetes. 2026;75(Suppl 1):1454-P. doi:10.2337/db26-1454-P
   

5. Hsu C, Lo SW, Nigam N, et al. PCSK9 inhibitors are associated with a lower risk of incident diabetes: a global real-world analysis. Diabetes. 2026;75(Suppl 1):1245-OR. doi:10.2337/db26-1245-OR