How does basal insulin compare to other diabetes medications in its impact on lipids, cholesterol and triglycerides?
Cardiovascular complications are a well-established risk among patients with type 2 diabetes. Components of the lipid profile, comprising total cholesterol, LDL-C, HDL-C, and triglycerides, play an essential role in driving this risk. Several studies have been completed regarding insulin and the chance for adverse cardiovascular outcomes, including the ORIGIN trial, which found no increase in the risk of cardiovascular death and non-fatal myocardial infarction in patients randomly assigned to glargine compared to the standard of therapy. Additionally, only a few studies directly evaluate the effect of different classes of antihyperglycemic agents on lipids, and none to date have compared the impact of these agents on basal insulin.
This study is a meta-analysis of randomized control trials that aims to evaluate the effect of basal insulin therapy on the lipid profile compared to other classes of antihyperglycemic agents in patients with type 2 diabetes. The literature was reviewed for RCTs that reported at least one lipid parameter – TC, LDL-C, HDL-C, or triglycerides – in patients with type 2 diabetes randomly assigned to basal insulin or any other class of antihyperglycemic medications up to October 2019. Twenty-three full-text articles were selected with a combined patient total of 14,133. Trials were excluded if they were nonrandomized, did not report any of the four lipid changes, did not report dispersion measures, or used either prandial or premixed insulin. All analysis was performed using a random-effects model, and the I2 statistic was used to assess heterogeneity among studies. In addition, subgroup analyses and meta-regression were used to investigate potential influences on lipid parameters, including weight and lifestyle changes. Of the 23 studies, 18 used insulin glargine, four used NPH, and one used insulin detemir. Noninsulin therapies included GLP-1 receptor agonists used in 12, TZDs were used in five, DPP-4 inhibitors in three, and metformin ± a sulfonylurea, considered the standard of care, was used in three.
GLP-1 receptor agonists were found to decrease total cholesterol (mean difference -3.80; 95% CI: -6.30 to -1.30 mg/dL) and decrease LDL-C (MD -4.17; 95% CI -6.04 to 2.30 mg/dL) compared to basal insulin. Additionally, this class was found to improve HDL-C, although this was not statistically significant. TZDs were found to increase total cholesterol (MD: 16.20; 95% CI: 9.09-23.31) and had a nonsignificant increase in LDL-C compared to basal insulin, although it is important to note that three of the five trials used rosiglitazone, which may have impacted these results. This class was also found to increase HDL-C (MD 3.55; 95% CI: 0.55-6.56 mg/dL). No differences in any of the types of lipids were seen with DPP-4 inhibitors compared to basal insulin. Lastly, there was no difference between basal insulin and metformin ± a sulfonylurea in TC, LDL-C, or HDL-C, although basal insulin did significantly improve triglyceride levels (MD: 3.8; 95% CI: 0.99-6.63 mg/dL) compared to the standard of care. No other drug class displayed a significant difference in triglyceride levels.
Compared to basal insulin, GLP-1 receptor agonists were found to decrease total cholesterol and LDL-C and improve HDL-C. TZDs were found to increase total cholesterol, had a nonsignificant increase in LDL-C, and increased HDL-C. DPP-4 inhibitors did not lead to any significant changes in any of the components of the lipid panel. Metformin ± a sulfonylurea did not lead to any substantial changes in total cholesterol, LDL-C, or HDL-C; however, basal insulin was found to significantly lower triglycerides. Several limitations of this study include that the reductions in the lipid profile could also have been impacted by weight loss and lifestyle changes. Additionally, patients in some trials were on lipid-lowering therapy, and there is no way to distinguish which specific agent was driving the lower lipid profile levels. Lastly, changes in the lipid profile were not the primary outcome in any RCTs, creating the possibility that these studies were not designed to detect this outcome.
It is uncertain whether these differences in the lipid panel are significant enough to change clinical outcomes and decrease the risk of cardiovascular events in patients with type 2 diabetes. An analysis done with statins supports reduced risk of coronary heart disease with lowered LDL-C, concluding that there was a relative reduction in major cardiovascular events by 21% for each mmol decrease in LDL-C. Another found that for each 1 mg/dL increase in HDL-C, the risk of coronary heart disease was decreased by 2-3%. Future studies could delve further into the significance of specific numerical drops in LDL-C, TC, and triglycerides and the increases in HDL-C to determine if there is clinical significance in the results from this meta-analysis.
- Compared to basal insulin, GLP-1 receptor agonists decrease total cholesterol and LDL-C, and TZDs were found to increase HDL-C.
- No difference was found with DPP-4 inhibitors or metformin ± a sulfonylurea with TC, LDL-C, or HDL-C, although triglycerides were significantly lower with insulin than the standard of care.
- Future studies are needed to determine whether the numerical drops detected in this study translate into a decreased risk of adverse cardiovascular outcomes in patients with type 2 diabetes.
Reference for “Effects of Basal Insulin on Lipids vs. Other Antihyperglycemics”:
Rigato, Mauro et al. “Effects of Basal Insulin on Lipid Profile Compared to Other Classes of Antihyperglycemic Agents in Type 2 Diabetic Patients.” The Journal of clinical endocrinology and metabolism vol. 105,7 (2020): dgaa178.
Jessica Rogers, PharmD candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences