Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk

Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.


Aim: To investigate the effects of semaglutide versus comparators on major adverse cardiovascular events (MACE: cardiovascular [CV] death, nonfatal myocardial infarction [MI] and nonfatal stroke) and hospitalization for heart failure (HF) in the SUSTAIN (subcutaneous semaglutide) and PIONEER (oral semaglutide) trials across subgroups of varying CV risk.

Methods: Post hoc analyses of individual patient-level data combined from SUSTAIN 6 and PIONEER 6 were performed to assess MACE and HF. MACE were analysed in subjects with and without: established CV disease and/or chronic kidney disease; prior MI or stroke; and prior HF. MACE in the SUSTAIN and PIONEER glycaemic efficacy trials were also assessed.

Results: In SUSTAIN 6 and PIONEER 6 combined, the hazard ratio (HR) for effect of semaglutide versus placebo on overall MACE was 0.76 (95% CI 0.62, 0.92), which was mainly driven by the effect on nonfatal stroke (HR 0.65 [95% CI 0.43, 0.97]). The HR for hospitalization for HF was 1.03 (95% CI 0.75, 1.40). The HRs for MACE were <1.0 in all subgroups, except for those with prior HF (HR 1.06 [95% CI 0.72, 1.57]); P-values for interaction of subgroup on treatment effect were >0.05, except for HF (0.046). In the combined glycaemic efficacy trials, the HR for effect of semaglutide versus comparators on MACE was 0.85 (95% CI 0.55, 1.33).

Conclusions: In SUSTAIN and PIONEER combined, glucagon-like peptide-1 analogue semaglutide showed consistent effects on MACE versus comparators across varying CV risk. No effect of semaglutide on MACE was observed in subjects with prior HF.

Trial registration: NCT02054897 NCT01930188 NCT01885208 NCT02128932 NCT02305381 NCT01720446 NCT02906930 NCT02863328 NCT02607865 NCT02863419 NCT02827708 NCT02692716 NCT02849080 NCT03021187 NCT03018028 NCT03015220.

Keywords: cardiovascular disease; clinical trial; glucagon-like peptide-1 analogue; phase III study; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptides / therapeutic use
  • Heart Disease Risk Factors
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Risk Factors


  • Hypoglycemic Agents
  • semaglutide
  • Glucagon-Like Peptides

Associated data

  • EudraCT/2013‐000632‐94
  • EudraCT/2012‐004827‐19
  • EudraCT/2012‐004826‐92
  • EudraCT/2013‐004392‐12
  • EudraCT/2013‐004502‐26
  • EudraCT/2012‐002839‐28
  • EudraCT/2015‐005622‐19
  • EudraCT/2015‐005209‐36
  • EudraCT/2015‐001351‐71
  • EudraCT/2015‐005210‐30
  • EudraCT/2015‐005326‐19
  • EudraCT/2015‐003563‐10
  • EudraCT/2015‐005593‐38
  • EudraCT/2016‐000988‐16