Research Achievements

Evidence map of glucose-lowering medications with cardiovascular outcomes

Last updated:2020-12-19

Considering the global burden of diabetes and associated cardiovascular disease, an urgent need exists for the best treatment, which should be based on the best available evidence.

Our study provides a quantitative comparison of the effects of various glucose-lowering medications on cardiovascular outcomes at both the individual drug and class level. In the form of an evidence map, the risk and benefit (Benefit/No effect/Harm) of each drug for different cardiovascular outcomes and the corresponding level of evidence (High/Moderate/Low/Very low) are displayed. Incorporation of high-level evidence from our findings could inform clinical guidelines and therapeutic choices for patients.

Dipeptidyl peptidase-4 (DPP-4) inhibitor and cardiovascular safety

In the overall analysis, DPP-4 inhibitors as a class had no significant effects on the risk of death from cardiovascular disease, major adverse cardiovascular events, myocardial infarction, stroke, heart failure, and unstable angina. Similar results were observed in meta-analyses of placebo-controlled studies.

Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular safety

In the overall analysis, GLP-1 receptor agonists as a class reduced the risk of major adverse cardiovascular events (RR 0.88; 95% CI 0.84–0.92), death from cardiovascular disease (0.87; 95% CI 0.81–0.94), myocardial infarction (0.92; 95% CI 0.86–0.99), stroke (0.84;95% CI 0.77–0.93), heart failure (0.90;95% CI  0.83–0.99), and atrial fibrillation (0.85; 95% CI 0.73–0.99). Similar results were observed in meta-analyses of placebo-controlled studies.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and cardiovascular safety

In the overall analysis, SGLT2 inhibitors as a class reduced the risk of major adverse cardiovascular events (RR 0.87; 95%CI 0.82–0.93), death from cardiovascular disease (0.82;95% CI 0.75–0.90), myocardial infarction (0.86; 95% CI 0.78–0.94), and heart failure (0.68; 95% CI 0.63–0.73). Similar results were observed in meta-analyses of placebo-controlled studies.

Sulfonylureas and cardiovascular safety

In the overall analysis, sulfonylureas as a class were neutral with regard to all cardiovascular outcomes. Among individual sulfonylureas, glipizide increased the risk of death from cardiovascular disease (RR 1.87; 95% CI 1.01–3.45) and glimepiride increased the risk of stroke (2.01; 95% CI 1.02–3.98).

Thiazolidinediones and cardiovascular safety

In the overall analysis, rosiglitazone increased the risk of myocardial infarction (RR 1.28; 95% CI 1.02–1.62) and heart failure (1.72, 95% CI 1.31–2.27); similar results were observed in meta-analyses of placebo-controlled studies. In the overall analysis, pioglitazone decreased the risk of major adverse cardiovascular events (RR 0.84; 95% CI 0.74–0.96), myocardial infarction (0.80;95% CI 0.67–0.95), and stroke (0.79; 95% CI 0.65–0.95), but increased the risk of heart failure (1.40; 95% CI 1.16–1.69). Similar results were observed in meta-analyses of placebo-controlled studies.

Biguanides and cardiovascular safety

In the overall analysis, metformin was neutral with regard to all cardiovascular outcomes, but results indicated that it might decrease the risk of major adverse cardiovascular events (RR 0.84; 95% CI 0.71–1.00) compared with placebo or no treatment.

α-glucosidase inhibitor and cardiovascular safety

Acarbose and voglibose were neutral with regard to all cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance.

Meglitinides and cardiovascular safety

Nateglinide was neutral for all cardiovascular outcomes among individuals with impaired glucose tolerance and with or at high risk of cardiovascular disease.

Bromocriptine and cardiovascular safety

Bromocriptine was neutral for all cardiovascular outcomes.

Insulin and cardiovascular safety

Insulin had no significant effects on the risk of cardiovascular disease, major cardiovascular events, myocardial infarction, stroke, or heart failure. Similar results were observed in the meta-analysis of degludec versus glargine.

 

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Figure 1. Evidence map of glucose-lowering medications on cardiovascular outcomes

We found varied levels of evidence for the associations between diabetes drugs and cardiovascular outcomes; some drugs raised the risk of cardiovascular disease, whereas others showed benefit.

 

Article Link: https://10.1016/S2213-8587(19)30422-X