IPM Take
The GLP-1 era is no longer about one drug class for diabetes, another for obesity and a separate pathway for heart disease. SURPASS-CVOT and the 2026 ADA Standards point toward a more integrated cardio-kidney-metabolic model, where the first injectable choice may affect cardiovascular outcomes, heart failure symptoms, kidney risk, weight and mortality. But evidence is moving faster than health systems. Without clear sequencing rules, reimbursement logic and referral pathways, “personalised cardiometabolic care” risks becoming another privilege for patients with the right insurance, specialist access and persistence.
Executive Summary
The 2026 American Diabetes Association Standards of Care recommend GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists across several cardiometabolic contexts, including type 2 diabetes with cardiovascular disease, obesity, chronic kidney disease and symptomatic heart failure with preserved ejection fraction where evidence supports benefit.
The SURPASS-CVOT trial compared Eli Lilly’s tirzepatide, a dual GIP/GLP-1 receptor agonist, with dulaglutide, an established GLP-1 receptor agonist, in more than 13,000 patients with type 2 diabetes and established cardiovascular disease. The main trial found that tirzepatide was non-inferior to dulaglutide for the composite of cardiovascular death, myocardial infarction or stroke. Lilly also reported an 8% lower rate of three-point major adverse cardiovascular events and a 16% lower rate of all-cause mortality with tirzepatide versus dulaglutide.
A 2026 JAMA Cardiology post hoc analysis of SURPASS-CVOT found that tirzepatide was associated with a lower incidence of a broader six-component cardiorenal composite outcome, including all-cause mortality, myocardial infarction, stroke, coronary revascularisation, hospitalisation for heart failure and adverse kidney outcomes. However, this was a secondary post hoc analysis, so it should inform pathway thinking rather than be treated as a stand-alone reimbursement verdict.
The ADA update also reflects evidence from heart failure trials, including SUMMIT, where tirzepatide reduced the risk of cardiovascular death or worsening heart failure and improved health status in patients with obesity and heart failure with preserved ejection fraction.
The implication is clear: GLP-1 and dual GIP/GLP-1 prescribing is becoming a pathway decision. Clinicians, payers and health systems will increasingly need to decide which patient gets semaglutide, tirzepatide, dulaglutide or another agent, when switching is justified, and whether access rules reflect cardiometabolic risk rather than narrow glucose thresholds.
Why it matters
- Policymakers and public authorities: Cardiometabolic policy needs to move beyond siloed diabetes, obesity, heart failure and kidney programmes. These drugs are forcing pathway integration.
- Payers and HTA bodies: Reimbursement decisions will need to address sequencing, switching, comparative effectiveness, cardiovascular outcomes, heart failure benefits, kidney outcomes, tolerability and affordability.
- Clinicians and providers: The “right” GLP-1 or dual agonist is increasingly patient-specific. ASCVD, obesity, HFpEF, CKD, weight-loss need, tolerability, adherence and access all matter.
- Industry and innovation partners: The market is shifting from weight-loss competition to outcomes competition. Cardiovascular and kidney data will increasingly define product positioning.
- Patients and advocates: The promise is more personalised treatment. The danger is that access rules may lag behind evidence, leaving patients stuck on the “available” drug rather than the best-fit drug.
The conversation around GLP-1 therapies no longer follows a straight line. What began as a discussion about glucose control has gradually unfolded into something far more complex and consequential.
At first, these medicines were framed as tools for managing diabetes. Then their impact on weight shifted the narrative toward obesity care. As evidence accumulated, their role in reducing cardiovascular risk brought them into yet another domain. Each step expanded their relevance, but also blurred the boundaries between specialties that once operated separately.
Now, the question facing clinicians is no longer simply whether to use a GLP-1 therapy, but how to choose among them. Which agent should come first? For which patient profile? And based on which outcomes?
This shift has been accelerated by the findings from SURPASS-CVOT and the updates in the 2026 ADA Standards of Care, both of which underscore that treatment decisions in this space are no longer interchangeable or purely metabolic.
SURPASS-CVOT compared tirzepatide with dulaglutide in patients with type 2 diabetes and established cardiovascular disease. This was not a placebo comparison. It was a head-to-head trial against an established GLP-1 receptor agonist with cardiovascular outcomes evidence.
That matters.
The trial found that tirzepatide was non-inferior to dulaglutide for the standard three-point cardiovascular endpoint: cardiovascular death, myocardial infarction or stroke. Lilly reported an 8% lower rate of these events with tirzepatide and a 16% lower rate of all-cause mortality compared with dulaglutide.
But the interpretation has to be disciplined.
Tirzepatide did not clearly rewrite the entire cardiovascular outcomes hierarchy on the primary endpoint. The key message is not that every patient should automatically switch. The more accurate message is that tirzepatide now has serious cardiovascular outcomes data in a high-risk type 2 diabetes population, alongside its stronger effects on weight and glycaemic control.
That makes prescribing more political.
Because once drugs differ not only in HbA1c and weight loss, but also in cardiovascular, kidney and heart failure evidence, payers can no longer pretend these medicines are interchangeable lifestyle products.
A 2026 JAMA Cardiology post hoc analysis pushed the debate further. Using a broader six-component cardiorenal endpoint, including all-cause mortality, myocardial infarction, stroke, revascularisation, hospitalisation for heart failure and adverse kidney outcomes, tirzepatide was associated with fewer events than dulaglutide.
This is exactly where the policy fight begins.
Post hoc analyses should not be over-sold. They are not the same as a primary trial endpoint. But they can expose where clinical reality is moving faster than reimbursement architecture. Patients with type 2 diabetes do not arrive with one isolated risk. They arrive with obesity, hypertension, fatty liver disease, kidney risk, heart failure risk, atherosclerosis, sleep problems and social barriers.
The old diabetes model was too narrow for that reality.
The ADA 2026 Standards reflect this shift. The guidance increasingly frames glucose-lowering therapy through cardiovascular, heart failure, kidney and weight-management benefit, not only HbA1c reduction. In adults with type 2 diabetes, obesity and symptomatic HFpEF, the Standards recommend including a dual GIP/GLP-1 receptor agonist or GLP-1 receptor agonist with demonstrated benefit for reducing heart failure events and symptoms.
That is a major signal.
It means GLP-1-based therapy is no longer sitting outside heart failure pathways. It is entering them.
The SUMMIT trial helped drive that change. In patients with obesity and HFpEF, tirzepatide reduced the risk of cardiovascular death or worsening heart failure and improved health status. This matters because HFpEF has long been a frustrating disease area, common, expensive and closely linked to obesity, diabetes and ageing, but historically difficult to treat.
The cardiometabolic map is being redrawn.
But health systems are not ready.
In practice, clinicians face a messy set of questions. Should a patient with type 2 diabetes and established ASCVD start on tirzepatide, semaglutide or dulaglutide? Should a patient doing well on dulaglutide switch because of weight, kidney or mortality signals? Should HFpEF symptoms change the first choice? Should CKD status change sequencing? What happens when the clinically preferred medicine is not covered?
This is where precision medicine collides with payer logic.
Guidelines can recommend integrated care. Trials can show benefit. But reimbursement systems still often operate through narrow categories: diabetes indication, obesity indication, cardiovascular indication, prior authorisation, BMI threshold, HbA1c threshold, step therapy, formulary preference, supply constraints and local budgets.
That creates a dangerous gap between evidence and access.
A patient may qualify clinically but not administratively. Another may receive an older or less suitable drug because it is cheaper or easier to authorise. Another may stop therapy because gastrointestinal adverse effects are not managed through proper titration and follow-up. Another may never reach a specialist who understands cardio-kidney-metabolic sequencing.
This is not personalised care. It is pathway roulette.
The next phase of GLP-1 policy needs to answer five questions.
First, who gets first-line access? High-risk patients with established ASCVD, CKD, obesity or HFpEF may need priority over lower-risk cosmetic or marginal-use markets.
Second, when is switching justified? Evidence must guide whether switching from one GLP-1 to another, or to a dual GIP/GLP-1 therapy, is clinically meaningful.
Third, how should outcomes be valued? HbA1c and weight loss are not enough. HTA bodies need to consider cardiovascular events, heart failure admissions, kidney outcomes, mortality, quality of life and treatment persistence.
Fourth, how will tolerability be managed? Gastrointestinal adverse effects and discontinuation matter. Access without follow-up is not access.
Fifth, will equity be protected? The patients with the highest cardiometabolic burden are often the same patients with the least access to specialist care, obesity services, diabetes technology and expensive medicines.
The GLP-1 boom has already exposed uncomfortable politics: who gets prevention, who gets treatment, who pays, who waits, and who is blamed for disease that health systems failed to prevent.
SURPASS-CVOT adds another layer.
It suggests that choosing within the GLP-1 and dual agonist class may become a serious cardiovascular decision. ADA 2026 makes that harder to ignore by embedding these therapies more clearly into heart failure and cardio-kidney-metabolic care.
That should not trigger simplistic prescribing hype.
It should trigger system design.
Cardiometabolic care now needs integrated pathways that connect primary care, endocrinology, cardiology, nephrology, obesity medicine and pharmacy. It needs reimbursement that follows risk, not just labels. It needs data systems that track outcomes after initiation and switching. It needs patient support that makes adherence possible.
The drug class has evolved, moving rapidly from a narrow focus on glucose control to a broader role in managing cardiovascular, kidney and metabolic risk. Yet the policy architecture surrounding these therapies has struggled to keep pace, still shaped by older categories, fragmented reimbursement rules and siloed care pathways. As a result, the gap between what is clinically possible and what is practically accessible continues to widen, and that gap may ultimately become the most significant barrier to real-world impact.
