new Therapies Expand Treatment Options for Metabolic Syndrome, Study Finds
June 17, 2024 – A recent review published in Pharmaceutics highlights the growing role of biologic medications in managing metabolic syndrome, offering increasingly targeted approaches beyond traditional therapies. The analysis details advancements in glucose and lipid control, emphasizing the comparative benefits and limitations of newer drug classes like GLP-1 receptor agonists, SGLT-2 inhibitors, and PCSK9 inhibitors.
The review, authored by Górecka et al., underscores how these biologics are changing the landscape of metabolic syndrome treatment. Regarding glucose control, the study notes that GLP-1 receptor agonists demonstrated a greater reduction in HbA1c compared to SGLT-2 inhibitors. Conversely, SGLT-2 inhibitors were found to reduce the risk of heart failure hospitalization, an effect not observed with GLP-1s. GLP-1s, however, showed a reduction in the risk of non-fatal stroke, while SGLT-2 inhibitors had a “minimal impact” on stroke risk.A noted side effect of SGLT-2 inhibitors is an increased risk of genitourinary tract infections, linked to their mechanism of renal glucose excretion. The authors cite a meta-analysis concluding that the optimal choice between these two classes depends on individual patient risk profiles.
The review also points to challenges with GLP-1 drug adherence. ”GLP-1 drugs ‘are differently tolerated by patients'” and exhibit poorer persistence compared to other glucose-lowering medications like DPP-4 inhibitors and sulfonylureas, frequently enough due to adverse effects.
Turning to lipid management, the study explains the function of PCSK9, a regulator of cholesterol metabolism, and its link to familial hypercholesterolemia through gain of function mutations discovered in the early 2000s. Since 2015, the FDA has approved two monoclonal antibodies targeting PCSK9 – alirocumab and evolocumab – and, more recently, inclisiran, a small interfering RNA (siRNA) that inhibits PCSK9 synthesis, has gained approval in both Europe and the US.
The authors state that PCSK9 inhibitors are currently the most effective therapeutic option for reducing total and LDL cholesterol. These drugs are typically used in conjunction with a statin or other cholesterol-lowering medication, or as monotherapy when statins are ineffective or poorly tolerated. While “highly effective” at improving lipid profiles,their higher cost limits their use primarily to patients whose cholesterol levels remain uncontrolled despite conventional treatments.
A cited meta-analysis showed PCSK9 inhibitors were more effective than statins at lowering total and LDL cholesterol and increasing HDL cholesterol. Importantly, the analysis found no notable differences between the two in terms of cardiovascular events or all-cause mortality. PCSK9 inhibitors also did not demonstrate the increased risk of liver enzyme elevation or diabetes associated with statins. Though,potential adverse effects like injection site reactions,flu-like symptoms,and upper respiratory tract infections may limit their use. the review also notes that a combination of statin plus ezetimibe proved superior to PCSK9 inhibitors for lowering triglyceride levels.
The full study, “Biological and Biosimilar Medicines in Contemporary Pharmacotherapy for Metabolic Syndrome,” is available in Pharmaceutics, 2025; 17(6):768. doi:10.3390/pharmaceutics17060768.
