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Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity

Educational Objective
To understand the benefits of metabolic surgery for patients with type 2 diabetes and obesity.
1 Credit CME
Key Points

Question  Is there an association between metabolic surgery and major adverse cardiovascular events (all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation) in patients with type 2 diabetes and obesity?

Findings  In this retrospective cohort study of 13 722 patients (including 2287 patients who underwent metabolic surgery and 11 435 matched controls), metabolic surgery was significantly associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.61).

Meaning  Among patients with type 2 diabetes and obesity, metabolic surgery was significantly associated with a lower risk of incident major adverse cardiovascular events.


Importance  Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized.

Objective  To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity.

Design, Setting, and Participants  Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018.

Exposures  Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity.

Main Outcomes and Measures  The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point.

Results  Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]).

Conclusions and Relevance  Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials.

Trial Registration Identifier: NCT03955952

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Steven E. Nissen, MD, Cleveland Clinic JB-20, 9500 Euclid Ave, Cleveland, OH 44195 (

Accepted for Publication: August 19, 2019.

Published Online: September 2, 2019. doi:10.1001/jama.2019.14231

Author Contributions: Dr Aminian and Mr Zajichek had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Aminian, Zajichek, Arterburn, Brethauer, Schauer, Nissen.

Acquisition, analysis, or interpretation of data: Aminian, Zajichek, Wolski, Schauer, Kattan, Nissen.

Drafting of the manuscript: Aminian, Nissen.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Aminian, Zajichek, Wolski, Nissen.

Obtained funding: Aminian.

Administrative, technical, or material support: Aminian, Zajichek, Wolski, Schauer, Nissen.

Supervision: Aminian, Arterburn, Kattan, Nissen.

Conflict of Interest Disclosures: Dr Aminian reported receiving grants from Medtronic. Dr Arterburn reported receiving grants from the National Institutes of Health (NIH) and the Patient-Centered Outcomes Research Institute and receiving nonfinancial support from International Federation for the Surgery of Obesity and Metabolic Disorders Latin America Chapter. Dr Brethauer reported receiving grants from Medtronic and GI Windows. Dr Schauer reported receiving grants from Medtronic, Ethicon, and Pacira and receiving personal fees from Medtronic, GI Dynamics, WL Gore and Associates, Becton Dickinson Surgical, and Global Academy for Medical Education. Dr Kattan reported receiving grants from Medtronic and Novo Nordisk. Dr Nissen reported receiving a grant from Medtronic for the current study and receiving research support from Amgen, AbbVie, AstraZeneca, Cerenis, Eli Lilly, Esperion Therapeutics, Novo-Nordisk, The Medicines Company, Orexigen, Pfizer, and Takeda and consulting for a number of pharmaceutical companies without financial compensation (all honoraria, consulting fees, or any other payments from any for-profit entity are paid directly to charity, so neither income nor any tax deduction is received). No other disclosures were reported.

Funding/Support: This study was partially funded by an unrestricted grant from Medtronic. Dr Arterburn was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK105960.

Role of the Funder/Sponsor: Medtronic had no role in the design and conduct of the study; collection, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Meeting Presentation: Presented at the European Society of Cardiology (ESC) Congress 2019; September 2, 2019; Paris, France.

Additional Contributions: We acknowledge Alex Milinovich, BA, and Jian Jin, MS, from Department of Quantitative Health Sciences, Cleveland Clinic, for creation of the database. Mssrs Milinovich and Jin did not receive compensation for their role in the study.

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