The effect of a dual combination of noninsulin antidiabetic drugs on lipids: a systematic review and network meta-analysis

Abstract

Objective:

As an ever widening array of anti-hyperglycemic agents are now available, the effect of these drugs on lipids is increasingly complex and controversial. The present meta-analysis was designed to clarify the effect of a dual combination of noninsulin anti-hyperglycemic agents on lipids in type 2 diabetes.

Methods:

Randomized controlled trials comparing different dual combinations of antidiabetic drugs were identified by searching PubMed, Cochrane Library, and Embase. Study selection, data abstraction and quality assessment were carried out by two reviewers independently. Change in low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride and total cholesterol were pooled by both traditional meta-analysis and network meta-analysis.

Results:

Eighteen studies with a total of 10,222 patients were included. Network meta-analysis suggested that metformin + dipeptidyl peptidase-4 inhibitors (DPP-4) (LDL cholesterol: −0.19 mmol/L; HDL cholesterol: 0.06 mmol/L; triglycerides: −0.73 mmol/L; total cholesterol: −0.4 mmol/L) and metformin + glucagon-like peptide-1 (GLP-1) agonist (LDL cholesterol: −0.3 mmol/L; HDL cholesterol: 0.06 mmol/L; triglycerides: −0.64 mmol/L; total cholesterol: −0.5 mmol/L) were associated with relatively larger beneficial effects on the lipid profile among all combinations. Compared with metformin + thiazolidinedione, metformin + GLP-1 agonist (mean difference: −0.38; 95% confidence interval [CI]: −0.66 to −0.10) significantly decreased LDL cholesterol. Metformin + thiazolidinedione showed a larger increase than metformin + sulfonylurea in HDL cholesterol (mean difference: 0.1; 95% CI: 0.01 to 0.21).

Conclusions:

The effect of a dual combination of noninsulin anti-hyperglycemic agents on lipids is moderate to small, with metformin + DPP-4 inhibitor and metformin + GLP-1 agonist showing consistent beneficial effects on LDL cholesterol, HDL cholesterol, triglycerides and total cholesterol. Future trials are needed to confirm these findings.

Keywords::

• Antidiabetic drugs
• Lipids
• Network meta-analysis
• Systematic review

Transparency

Declaration of funding

This study is not funded.

Author contributions: conception and design: P.F.; selection and screening of trials included in the analysis: X.D., H.W.; data extraction and analysis: X.D., H.W., Z.J.; writing paper: X.D., H.W.; manuscript revision: Z.J., P.F. X.D. and H.W. contributed equally and should be considered co-first authors.

Declaration of financial/other relationships

X.D., H.W., Z.J., and P.F. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.