Background
Biguanides
Metformin
Cardiovascular safety
Summary
Insulin secretagogues
Sulfonylureas
Cardiovascular safety
Summary
Meglitinides
Cardiovascular safety
Summary
Thiazolidinediones
Cardiovascular safety
Summary
Incretin-based drugs
Dipeptidyl peptidase-4 inhibitors
Cardiovascular safety
Summary
Glucagon-like peptide-1 agonists
Cardiovascular safety
Summary
Sodium glucose cotransporter-2 inhibitors
Cardiovascular safety
Summary
Alpha glucosidase inhibitors
Cardiovascular safety
Summary
Conclusions
Metformin | Sulfonylureas | Meglitinides | TZDs | DPP-4 inhibitors | GLP-1 agonists | SGLT-2 inhibitors | AGIs | |||
---|---|---|---|---|---|---|---|---|---|---|
1st generation | 2nd and 3rd generation | Rosiglitazone | Pioglitazone | |||||||
Relative glycemic efficacy | +++ | +++ | + | +++ | ++ | +++ | ++ | ++ | ||
Effect on weight | Loss/neutral | Gain | Gain | Gain | Gain | Gain | Neutral | Loss | Loss | Neutral |
Overall CV safety | Benefit | Caution | Neutral | No data | Caution | Likely benefit | Neutral | Benefit | Benefit | No data |
Significant side effects | Lactic acidosis | Profound hypoglycemia, secondary failure | Hypoglycemia | Association with increased fracture risk, bladder cancera
| GI effects, acute pancreatitisa
| GI effects | Ketoacidosis, UTI | Flatulence, diarrhea |
Acceptable | Avoid | No data |
---|---|---|
Established or at risk of heart failure
| ||
Metformin | TZDs | Meglitinides |
Sulfonylureas | DPP-4 inhibitorsa
| AGIs |
SGLT-2 inhibitors | ||
Established cardiovascular disease
| ||
Metformin | 1st generation sulfonylureas | Meglitinides |
2nd and 3rd generation sulfonylureas | Rosiglitazone | AGIs |
Pioglitazone | ||
DPP-4 inhibitors | ||
SGLT-2 inhibitors |
Study | Drug | Comparator | Primary endpoint | Results |
---|---|---|---|---|
CANVAS | Canagliflozin | Placebo | Major adverse cardiovascular events, including CV death, non-fatal MI, and non-fatal stroke | 2017 |
CARMELINA | Linagliptin | Placebo | Composite endpoint: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for unstable angina pectoris | 2018 |
EXSCEL | Exenatide once weekly | Placebo | Composite endpoint: cardiovascular death, non-fatal MI, or non-fatal stroke | 2018 |
REWIND | Dulaglutide | Placebo | Composite endpoint: cardiovascular death, non-fatal MI, or non-fatal stroke | 2018 |
DECLARE-TIMI 58 | Dapagliflozin | Placebo | Composite endpoint: CV death, MI or ischemic stroke | 2019 |
CAROLINA | Linagliptin | Glimepiride | Composite endpoint: CV death, non-fatal MI (excluding silent MI), non-fatal stroke and hospitalisation for unstable angina pectoris | 2019 |