Association of Hypoglycemic Treatment Regimens on Cardiovascular Outcomes in Overweight and Obese Subjects With Type 2 Diabetes

A Substudy of the SCOUT Trial

  1. Charlotte Andersson, MD, PHD9
  1. 1Department of Clinical Physiology, Nuclear Medicine, Positron Emission Tomography, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
  2. 2The Heart Center, Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
  3. 3Institute of Cardiovascular Science, University College London, London, United Kingdom
  4. 4London School of Hygiene and Tropical Medicine, London, United Kingdom
  5. 5Royal Alexandra Hospital, The University of Alberta, Edmonton, Canada
  6. 6The Boden Institute, University of Sydney, Sydney, Australia
  7. 7Endocrinology, Obesity, and Eating Disorders Research Group, Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil
  8. 8Department of Diabetology, Metabolism, and Clinical Nutrition, Antwerp University Hospital, Antwerp, Belgium
  9. 9Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark
  1. Corresponding author: Adam Ali Ghotbi, adamghotbi{at}


OBJECTIVE To assess the association of hypoglycemic treatment regimens on cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk.

RESEARCH DESIGN AND METHODS This analysis included 8,192 overweight patients with type 2 diabetes mellitus from the Sibutramine Cardiovascular Outcomes Trial (SCOUT) randomized to lifestyle intervention with or without sibutramine for up to 6 years. Patients were grouped according to hypoglycemic treatment at baseline. The primary end point was the time from randomization to the first occurrence of a primary outcome event (POE), nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death. Multivariable Cox proportional hazards regression models were used to assess the impact of antiglycemic treatment on POE and all-cause mortality.

RESULTS Treatments for type 2 diabetes were as follows: diet alone (n = 1,394 subjects); metformin monotherapy (n = 1,631); insulin monotherapy (n = 1,116); sulphonylurea monotherapy (n = 1,083); metformin plus sulphonylurea (n = 1,565); and metformin plus insulin (n = 1,000); 905 subjects experienced a POE and 708 died. Metformin monotherapy was associated with lower risk of POE than insulin (hazard ratio [HR], 0.74; 95% CI, 0.57–0.95; P = 0.02). Diet alone also was associated with lower risk of POE (HR, 0.65; 95% CI, 0.48–0.87; P = 0.004). Metformin monotherapy also was associated with lower mortality (HR, 0.73; 95% CI, 0.54–0.99; P < 0.05), whereas no other monotherapies or combination therapies were significantly associated with POE or all-cause mortality compared with insulin as monotherapy.

CONCLUSIONS In obese patients with type 2 diabetes and high risk of cardiovascular disease, monotherapy with metformin or diet-only treatment were associated with lower risk of cardiovascular events than treatment with insulin.

  • Received January 4, 2013.
  • Accepted May 1, 2013.

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