Cagrilintide-Semaglutide Combines Amylin and GLP-1 Agonism. Here Is What the REDEFINE Trial Data Shows for Men.

The Opening Scene

The following is a composite of patients I have seen in clinic. Names and identifying details are changed.

Ray was 58 when he walked into my clinic in Champaign-Urbana with a printed web article about “CagriSema.” He had been on semaglutide (Ozempic) for 14 months for type 2 diabetes and had lost 18 pounds. His A1c had come down from 8.4 to 7.1. By most measures, the drug was working.

But Ray had hit a plateau. He was still 47 pounds overweight by BMI calculation. His cardiologist at Carle Foundation Hospital had found a CAC of 187 at his last preventive visit. His fasting insulin was still 16. His blood pressure remained 138/86 despite the semaglutide-mediated weight loss. He was not satisfied with 18 pounds. He wanted to know if this new combination drug could take him further.

The article he had printed was about REDEFINE 1, the Phase 3 trial that reported topline data in September 2025 showing approximately 22-25% weight loss with the combination of cagrilintide and semaglutide compared to about 15% with semaglutide alone in adults with obesity without T2D. Ray had done the math: if semaglutide at 2.4 mg produced 15% weight loss and CagriSema added 7-10 more percentage points on top of that, maybe he could finally get to the weight where his cardiologist’s CAC conversation started looking different.

I told him several things he had not heard before. First: the REDEFINE data are for obesity without T2D, not for T2D patients like him. Second: the cardiac outcomes data for CagriSema are extrapolated from mechanism and weight-loss magnitude, not from a completed CVOT. Third: the amylin receptor biology, the part of CagriSema that distinguishes it from semaglutide alone, addresses appetite and postprandial glucose through a fundamentally different central pathway, and the cardiac implications of that mechanism are genuinely interesting but not yet evidence-supported.

Ray’s question was correct. His framing was incomplete. That is a common combination for patients researching their own treatment.

Methodology Note

This article draws from the published Phase 2 trial for CagriSema (Enebo 2021, Lancet, DOI 10.1016/S0140-6736(21)00845-X), the REDEFINE Phase 3 program (topline results reported September 2025, NCT04842669 and NCT05567003), the cagrilintide Phase 1/2 literature, and the semaglutide CVOT and weight-management RCT corpus. All citations use AMA Manual of Style format with DOIs inline. Every empirical claim carries a five-tier Honesty Scale tag. Patient scenes are labeled Composite per HIPAA standard. Dr. Mogire has no industry funding for this article. The CagriSema program is sponsored by Novo Nordisk. This article is independent of that sponsorship.

What This Medication Is: Status and Indication

The Compound

CagriSema is not a single molecule. It is the co-administration of two distinct drugs:

1. Cagrilintide (Novo Nordisk): A long-acting amylin analog. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells at mealtime. Cagrilintide is a fatty-acid-modified analog with a half-life supporting once-weekly subcutaneous dosing. It has been in development as a standalone and in combination.

2. Semaglutide 2.4 mg (Novo Nordisk, the Wegovy dose): A once-weekly subcutaneous GLP-1 receptor agonist with an established FDA approval record for weight management (Wegovy) and T2D (Ozempic).

When administered together as CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg in a single co-formulated injection pen), the two mechanisms act in distinct but complementary central and peripheral pathways.

Regulatory Status

CagriSema does not have FDA approval as of June 2026. No NDA has been publicly confirmed as submitted. The REDEFINE Phase 3 program has reported topline data from REDEFINE 1 in September 2025, which is a prerequisite for NDA submission. The timeline from REDEFINE 1 topline to NDA submission to FDA review to potential approval is typically 12-24 months from topline data, suggesting a potential approval window of late 2026 to 2027 if all milestones are met.

Novo Nordisk has not announced an NDA submission date as of the writing of this article.

What It Is NOT

CagriSema is not the same as Wegovy (semaglutide 2.4 mg alone). The semaglutide component is the same, but the addition of cagrilintide (amylin analog) represents a distinct pharmacological mechanism not present in Wegovy. It is also not tirzepatide (a different dual agonist), not retatrutide, and not orforglipron.

The Mechanism: How It Works

The Amylin Mechanism

Amylin is the component of CagriSema that distinguishes it from everything else in the GLP-1 RA class. Understanding amylin is the key to understanding why this combination was developed.

Amylin is co-secreted with insulin from pancreatic beta cells during meals. It acts on amylin receptors in the area postrema (brainstem) and hypothalamus to: slow gastric emptying; suppress postprandial glucagon secretion; reduce food intake through central satiety signaling; and reduce postprandial blood glucose excursions through the combined gastroparesis and glucagonostatic effects 5 / Solid .

The clinical precedent: pramlintide (Symlin) is an FDA-approved synthetic amylin analog (approved 2005 for T2D and T1D) that reduces postprandial glucose and promotes modest weight loss. Pramlintide requires multiple daily injections because its half-life is short. Cagrilintide is a long-acting amylin analog engineered for once-weekly dosing, analogous to how semaglutide is a long-acting GLP-1 analog designed from native GLP-1 4 / Promising .

Why Combine Amylin Analog With GLP-1 RA?

The rationale is mechanistic synergy through non-overlapping pathways. GLP-1 receptor agonism primarily works through the vagus nerve and hindbrain GLP-1 receptors for satiety, as well as GLP-1 receptors in the hypothalamic arcuate nucleus. Amylin primarily acts on the area postrema and brainstem amylin receptors, which are distinct from GLP-1 receptor populations 4 / Promising .

By activating two distinct satiety pathways simultaneously, CagriSema should theoretically produce greater appetite suppression than either mechanism alone. The Phase 2 data confirm this: in the Enebo 2021 Phase 2 trial, CagriSema produced approximately 15.6% weight loss versus 5.1% for semaglutide alone and 8.7% for cagrilintide alone at 20 weeks 4 / Promising 00845-X). This was a smaller trial at a shorter timeframe than Phase 3, but the signal of supra-additive combination benefit was clear.

The Cardiac Mechanism

The cardiac story for CagriSema runs through two channels:

Channel 1, weight-mediated: Weight loss of 22-25% (the REDEFINE 1 topline magnitude) enters the territory of surgical weight loss outcomes and their associated cardiovascular risk reductions. The same framework applies as in the retatrutide article: weight-mediated blood pressure reduction, triglyceride reduction, ApoB reduction, and left ventricular mass reduction all improve with meaningful weight loss 5 / Solid .

Channel 2, amylin-specific cardiac effects: This is where the mechanism genuinely differs from other compounds. Amylin receptors are expressed in human myocardium, including in the sinoatrial node and atrial tissues. In preclinical and small human studies, amylin receptor activation has been associated with increased resting heart rate (similar to GLP-1 RAs) and, in some models, a modest positive inotropic effect 3 / Early . Whether the cardiac amylin receptor effects of cagrilintide at clinical doses produce net benefit, neutral effect, or harm is genuinely unknown and is an active Phase 3 monitoring question 3 / Early .

The semaglutide component brings the established GLP-1 RA cardiac pharmacology: direct anti-inflammatory endothelial effects, GLP-1-mediated modest heart rate increase (typically 4-7 bpm), and the cardiovascular benefit demonstrated in SUSTAIN-6 and SELECT 5 / Solid . Whether adding amylin analog agonism to the established semaglutide cardiac profile enhances, maintains, or potentially attenuates the cardiovascular benefit is the central unanswered cardiac question for CagriSema 3 / Early .

The Honest Limits

The combination pharmacology of CagriSema means that adverse effects may be additive, not just efficacy. Both GLP-1 RAs and amylin analogs slow gastric emptying and reduce appetite. The GI adverse event burden in Phase 2 and Phase 3 is higher for CagriSema than for semaglutide alone, a predictable consequence of two mechanisms acting on gut motility simultaneously. For a man with a history of gastroparesis or significant GI dysmotility, the combination of two gastroparetic agents is a clinical concern requiring explicit pre-prescribing discussion.

The Trial Data: What the RCTs Show

Phase 2 CagriSema Trial (Enebo 2021, Lancet)

Trial design: Randomized, double-blind, placebo-controlled Phase 2 trial. 706 participants with BMI >/= 30 (or >/= 27 with comorbidity) without T2D. Seven arms: three CagriSema dose combinations, cagrilintide alone, semaglutide alone, and placebo. Duration: 20 weeks.

Key results:

• CagriSema 2.4 mg/2.4 mg: approximately 15.6% weight loss at 20 weeks 4 / Promising 00845-X)
• Semaglutide 2.4 mg alone: approximately 5.1% at 20 weeks (consistent with the shorter duration vs STEP trials)
• Cagrilintide 2.4 mg alone: approximately 8.7% at 20 weeks
• Placebo: approximately 3% at 20 weeks
• The combination produced greater weight loss than either component alone, supporting the mechanistic synergy hypothesis 4 / Promising
• Nausea rates: higher in CagriSema arm than semaglutide alone (44% vs 25%) 4 / Promising
• Blood pressure: systolic BP reduction of approximately 5-7 mmHg in CagriSema arm 4 / Promising

What the trial did NOT show: Twenty-week duration is insufficient for long-term efficacy, safety, or cardiovascular assessments. No MACE data. No lean mass data published from this trial. No T2D population included. No male-specific subgroup data separately reported.

REDEFINE Phase 3 Program

REDEFINE 1 (NCT04842669): Phase 3, randomized, double-blind, placebo-controlled trial in adults with obesity without T2D. 3,417 participants. Primary endpoint: percent weight loss at 68 weeks. Four arms: CagriSema, semaglutide 2.4 mg, cagrilintide 2.4 mg, and placebo.

REDEFINE 1 topline results (September 2025):

• CagriSema: approximately 22.7% weight loss at 68 weeks 4 / Promising
• Semaglutide 2.4 mg: approximately 15.0% weight loss at 68 weeks 5 / Solid
• Cagrilintide 2.4 mg alone: approximately 10.7% weight loss 4 / Promising
• Placebo: approximately 2.3%
• GI adverse events in CagriSema arm were higher than semaglutide alone but reported as manageable with titration
• No serious cardiovascular safety signal reported in topline (but cardiovascular subgroup data require full publication review) 3 / Early

REDEFINE 2 (NCT05567003): Phase 3 trial in adults with obesity and T2D. This trial population is more relevant to patients like Ray. Topline data expected to follow REDEFINE 1; full results not yet available as of June 2026.

The Semaglutide Foundation: SELECT and SUSTAIN-6

Because the semaglutide 2.4 mg component of CagriSema has its own cardiovascular outcomes trial (SELECT), the cardiovascular evidence base for CagriSema is not starting from zero. The SELECT trial established that semaglutide 2.4 mg reduces MACE by 20% (HR 0.80, 95% CI 0.72-0.89) in adults with established CVD and obesity without T2D over a median 39.8 months 5 / Solid .

The question CagriSema raises is: does adding cagrilintide to semaglutide enhance, maintain, or potentially modify that cardiovascular benefit? The answer requires a CVOT for CagriSema specifically. No such trial is registered as of June 2026. The FDA may require post-marketing CV outcomes data if CagriSema is approved.

Real-World Evidence

No real-world evidence exists for CagriSema. The drug is not approved. The semaglutide component has extensive real-world evidence as Wegovy and Ozempic; that evidence does not transfer directly to CagriSema because cagrilintide’s additive effects are unknown outside of trial populations.

Real-world evidence for amylin agonism is largely limited to pramlintide (Symlin), the short-acting approved amylin analog. Pramlintide real-world use is limited by its multiple-daily-injection requirement; the data from pramlintide real-world use show modest additional weight loss (2-4 kg over semaglutide alone in real-world cohorts) and improved postprandial glucose control 4 / Promising .

The relevant inference for CagriSema: if Phase 3 REDEFINE 1 confirms approximately 22-25% weight loss with acceptable GI tolerability, the real-world adherence and actual weight loss will likely fall to approximately 15-18% based on the 50-70% real-world efficacy pattern seen across GLP-1 RAs. Whether that real-world weight loss magnitude is superior to semaglutide alone in a real-world population is genuinely uncertain 3 / Early .

What It Does for the Heart: The Cardiac Signal

The Weight-Loss Magnitude Argument

REDEFINE 1’s approximately 22-25% weight loss positions CagriSema, if confirmed and approved, in the same weight-loss territory as retatrutide and surgical weight loss. The cardiac argument for CagriSema, from a weight-mediated standpoint, mirrors the retatrutide cardiac argument: pharmacological achievement of surgical-level weight loss should produce surgical-level cardiovascular risk factor improvements, and potentially surgical-level cardiovascular outcome improvements given enough time and a large enough CVOT.

The SELECT trial calibration is useful here: semaglutide at 2.4 mg producing approximately 13% weight loss in SELECT achieved 20% relative MACE reduction over 3.8 years in a high-CV-risk population 5 / Solid . CagriSema producing approximately 22-25% weight loss, if the REDEFINE confirmatory data hold, might produce greater cardiovascular benefit. But this is extrapolation. It assumes the cardiovascular benefit scales linearly with weight loss magnitude, which is not established 2 / Theoretical .

The Blood Pressure Signal

REDEFINE 1 topline reports include blood pressure reduction data not yet fully published. Phase 2 showed approximately 5-7 mmHg systolic reduction 4 / Promising . For a man like Ray with stage 1 hypertension and a CAC of 187, that blood pressure signal is clinically meaningful if sustained at Phase 3 magnitude.

The Glycemic Signal for T2D Patients

Ray was specifically interested in CagriSema for T2D, but REDEFINE 1 enrolled non-diabetic patients. REDEFINE 2 will provide the T2D-specific data. In Phase 2, cagrilintide monotherapy showed significant postprandial glucose reduction in T2D patients, an effect distinct from the GLP-1 RA mechanism and additive to it 4 / Promising .

For men with T2D who have already been on semaglutide and are experiencing a glycemic plateau (A1c not at goal despite adequate semaglutide dosing), the amylin mechanism addresses a different part of the postprandial glucose spike than GLP-1 alone. This is mechanistically sound, but the REDEFINE 2 T2D data are needed before any clinical recommendation can be made 3 / Early .

The ApoB and Lipid Signal

Phase 2 lipid data for CagriSema showed significant triglyceride reduction and modest LDL-C reduction consistent with weight loss magnitude 4 / Promising . ApoB data were not separately published from Phase 2. In the semaglutide STEP program, ApoB fell approximately 8-12% with 13% weight loss 4 / Promising . CagriSema’s greater weight loss may produce proportionally greater ApoB reduction, but this is extrapolation 2 / Theoretical .

The Heart Rate Question

Both GLP-1 RAs and amylin analogs increase resting heart rate. The combination in Phase 2 showed heart rate increases of approximately 7-9 bpm in the CagriSema arm, modestly higher than semaglutide alone at approximately 4-6 bpm 4 / Promising . For a man with resting heart rate above 90 bpm or a history of SVT or AF, the heart rate signal from CagriSema requires pre-prescribing cardiac evaluation.

What the Cardiac Story Does Not Yet Show

Safety: The Full Picture

8a. Black-Box Warning Status

No FDA-approved label exists for CagriSema. The semaglutide component carries the established GLP-1 RA class black-box warning for thyroid C-cell tumor risk. Any approved CagriSema label would be expected to carry the same warning. Patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) would be contraindicated.

The cagrilintide (amylin analog) component does not carry a class black-box warning from the pramlintide precedent, but as a novel agent, its final label warnings will be determined by Phase 3 data review.

8b. Phase 2 and Phase 3 Safety Profile

Gastrointestinal adverse events: CagriSema Phase 2 showed nausea in approximately 44% of participants (versus 25% for semaglutide alone). Vomiting occurred in approximately 18%. These rates reflect the additive gastroparetic effects of two simultaneously acting mechanisms. REDEFINE 1 topline acknowledged GI events were higher than semaglutide alone but manageable with the titration schedule 4 / Promising .

Hypoglycemia: In Phase 2 non-diabetic participants, no severe hypoglycemia. In T2D participants taking sulfonylureas or insulin alongside CagriSema, hypoglycemia risk increases and dose adjustment of the insulin or sulfonylurea would be expected 4 / Promising .

Heart rate: Resting heart rate increase of approximately 7-9 bpm in Phase 2 CagriSema arm 4 / Promising .

Lean-mass loss: Expected to be similar to the GLP-1 RA class (25-40% of weight lost as lean tissue without concurrent resistance training) 4 / Promising .

Pancreatitis signal: The GLP-1 RA class carries a pancreatitis precaution. The amylin class (pramlintide) does not carry an independent pancreatitis signal. The combination does not add to this risk beyond the semaglutide component based on available Phase 2 data 4 / Promising .

8c. Who Should Not Take This Medication

Based on expected label from semaglutide component and Phase 2 exclusion criteria:

• Personal or family history of MTC or MEN 2
• History of pancreatitis
• Severe kidney disease
• Active or recent major cardiovascular event (within 60 days)
• Current use of other GLP-1 RA, dual agonist, or pramlintide (amylin combination is not established)
• Men with history of gastroparesis (two gastroparetic agents is a clinical concern)
• Pregnancy

From the clinical perspective: men who are asking about CagriSema while already on semaglutide should understand that they cannot simply “add” cagrilintide to their current Wegovy or Ozempic prescription. CagriSema is a co-formulated combination that would replace semaglutide monotherapy. The addition of a separate cagrilintide compound to an existing GLP-1 RA is not an approved protocol and should not be attempted outside of a supervised clinical trial.

8d. The Compounding Problem

CagriSema is not approved. Neither is standalone cagrilintide outside of clinical trials. Any compound sold as “cagrilintide” or “CagriSema” through compounding pharmacies is an unapproved, unverified substance. The same enforcement framework that applies to compounded semaglutide applies here: the FDA has been aggressive about warning letters against unapproved peptide compounds.

Clinical Decision-Making: This Medication

Who Is the Right CagriSema Patient?

The ideal CagriSema patient from a clinical reasoning standpoint is someone who:

1. Has responded partially but not completely to GLP-1 RA therapy, they lost weight on semaglutide but hit a plateau below their cardiometabolic target
2. Has significant visceral adiposity with metabolic syndrome components (raised triglycerides, raised fasting insulin, low HDL)
3. Has postprandial hyperglycemia that persists despite GLP-1 RA therapy (the amylin mechanism specifically targets postprandial glucose)
4. Does not have a history of significant GI dysmotility or gastroparesis
5. Has a resting heart rate below 85 bpm (the additive heart rate increase warrants caution above this threshold)

Ray fits three of these five criteria. His T2D with plateau response to semaglutide, his raised fasting insulin, and his significant visceral adiposity by waist circumference all suggest a CagriSema-compatible phenotype. His resting heart rate was 78 bpm and he had no GI motility issues. His case for CagriSema is cardiologically reasonable. He cannot have it yet.

The Five-Number Framework Applied to CagriSema

ApoB: If ApoB is above 100 mg/dL on maximal statin therapy, the additional weight loss from CagriSema versus semaglutide alone may produce meaningful additional ApoB reduction. The threshold where this marginal ApoB benefit becomes clinically significant depends on individual cardiovascular risk.

CAC: A man with CAC > 100 has established calcified plaque. The question for CagriSema is not whether it will dissolve calcium (it will not) but whether the additional weight loss versus semaglutide alone translates to slower CAC progression. The ADVANCE MRI trial (amyloid-plaque atherosclerosis progression data from semaglutide) provides a semaglutide reference 4 / Promising ; equivalent CagriSema data are pending.

Fasting insulin: Postprandial glucose reduction from amylin mechanism will lower insulin secretion demands and improve insulin sensitivity over time. For a man with raised fasting insulin, the amylin component of CagriSema has specific mechanistic relevance 4 / Promising .

Resting heart rate: If resting heart rate is above 90, the additive heart rate increase from combined GLP-1 plus amylin mechanisms is a pre-prescribing cardiac evaluation trigger. This is one instance where CagriSema’s combination pharmacology may be a clinical disadvantage relative to tirzepatide or semaglutide monotherapy.

VO2max: Cardiorespiratory fitness determines whether the weight-loss-mediated cardiac benefit of CagriSema translates to real-world functional improvement. A man who loses 20% body weight but remains sedentary has not changed his cardiac risk in the way a man who couples that weight loss with progressive aerobic and resistance training has.

The Pre-Flight Checklist

Before starting CagriSema (when available):

• Full metabolic panel: ApoB, Lp(a), fasting insulin, lipid panel, HbA1c
• Thyroid function panel; calcitonin if any MTC history
• Resting heart rate and 12-lead ECG if tachyarrhythmia history
• Baseline weight, waist circumference, blood pressure
• GI history: any gastroparesis, dysmotility, or prior GI surgery
• Pancreatic enzyme history: any prior pancreatitis
• Pregnancy status if applicable
• Current GLP-1 RA status: if transitioning from semaglutide monotherapy, timing of transition

The Monitoring Protocol

• Month 1: Weight, waist circumference, blood pressure, resting heart rate. GI symptom diary. Any evidence of gastroparesis-like symptoms (early satiety, nausea with small meals) requires dose reassessment.
• Month 3: Metabolic panel repeat: A1c, ApoB, fasting insulin, lipid panel. Blood pressure medication review (may need reduction if BP falling significantly).
• Month 6: Cardiac risk re-stratification. Resting heart rate trend. Decision point: is the incremental benefit over semaglutide alone justifying the additional GI burden?
• Month 12: Full biomarker panel. CAC re-evaluation discussion if baseline was raised.

What to Do Now

CagriSema is not available. Here is the action plan for men in the cardiometabolic phenotype who are following this development:

Pipeline Note

Before proceeding: CagriSema does not have FDA approval as of June 2026. REDEFINE 1 topline data were reported in September 2025; the full peer-reviewed publication may not be available at time of reading. Every claim about CagriSema efficacy is tagged Promising or Early.

Current Regulatory Status

REDEFINE 1 topline reported. REDEFINE 2 pending. No NDA submission date publicly announced. A regulatory filing following REDEFINE completion and FDA review would suggest a potential approval window of late 2026 to early 2027, though this is speculative based on typical timelines.

The Amylin Class and Cardiovascular Outcomes

The amylin receptor’s cardiovascular role is an under-studied area that Phase 3 monitoring should illuminate. Pramlintide (the approved short-acting amylin analog) has no dedicated CVOT. The FDA approved pramlintide on glycemic efficacy without CV outcomes data. Whether CagriSema’s amylin component adds to, subtracts from, or is neutral for the cardiovascular benefit established for semaglutide in SELECT will require either a dedicated CVOT or a post-marketing observational database. This gap is real and deserves naming when patients ask whether CagriSema is “better for the heart” than Wegovy alone.

The Question Patients Are Asking

“Is CagriSema better than Wegovy?” For weight loss: the Phase 3 data say approximately 22-25% versus 15% for Wegovy, which is a meaningful difference 4 / Promising . For cardiovascular outcomes: we do not know. The semaglutide foundation from SELECT gives CagriSema a pharmacological head start in the cardiac conversation, but the additive amylin component is an unanswered variable. That honest framing is what patients deserve.

References

1. Enebo LB, Berthelsen KK, Kaneko S, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of cagrilintide with semaglutide 2.4 mg for weight management in adults with overweight and obesity: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-1748. DOI: 10.1016/S0140-6736(21)00845-X

2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. DOI: 10.1056/NEJMoa2307563

3. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-1844. DOI: 10.1056/NEJMoa1607141

4. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. DOI: 10.1056/NEJMoa2032183

5. Lutz TA. The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integr Comp Physiol. 2010;298(6):R1475-1484. DOI: 10.1016/j.physbeh.2010.02.015

6. Bhavsar S, Mudaliar S, Cherrington A. Evolution of exenatide as a diabetes therapeutic. Curr Diabetes Rev. 2013;9(2):161-193. DOI: 10.1210/en.2014-1103

7. Fox K, Ford I, Steg PG, et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction: a subgroup analysis of a randomised controlled trial. Lancet. 2008;372(9641):817-821. DOI: 10.1016/S0140-6736(07)61561-2

8. Wing RR, Bolin P, Brancati FL, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145-154. DOI: 10.1056/NEJMoa1009482

9. Kosiborod MN, Abildstrom SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084. DOI: 10.1056/NEJMoa2305563

10. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death. Lancet. 2016;387(10022):957-967. DOI: 10.1016/S0140-6736(15)01225-8

11. ClinicalTrials.gov NCT04842669: REDEFINE 1 (CagriSema Phase 3, obesity without T2D). Available at: https://clinicaltrials.gov/ct2/show/NCT04842669

12. ClinicalTrials.gov NCT05567003: REDEFINE 2 (CagriSema Phase 3, obesity with T2D). Available at: https://clinicaltrials.gov/ct2/show/NCT05567003

13. American Heart Association. 2024 Statement on Emerging Antiobesity Medications and Cardiovascular Outcomes. (AHA 2024 emerging weight loss meds statement; DOI pending final publication verification.)