Metabolic syndrome

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Tirzepatide

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist undergoing trials for weight management. In a phase 3 double-blind, randomized, controlled trial, including 2539 adults with a BMI ≥30 kg/m2 or ≥27 kg/m2 with at least one obesity-related complication, tirzepatide reduced BMI by 15% to 21% at varying doses, compared with a reduction of 3.1% with placebo.[178] Tirzepatide is currently approved only for the treatment of type 2 diabetes mellitus.

11beta-hydroxysteroid dehydrogenase type 1 inhibitors

Emerging data from animal and human studies indicate an association of 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) over-expression with obesity and disorders in glucose and lipid metabolism. This has led to the hypothesis that selective inhibition of 11-beta-HSD1 could be used to treat metabolic syndrome and diabetes. Except for natural products and older agents, such as thiazolidinediones and fibrates, novel compounds, such as adamantyltriazoles, arylsulfonamidothiazoles, anilinothiazolones, BVT2733, INCB-13739, MK-0916, and MK-0736 are currently under investigation. The preliminary findings show a favorable effect on glucose and lipid metabolism, weight reduction, and adipokine levels.[179][180]

Peroxisome proliferator-activated receptor-delta (PPAR-delta) agonists

PPAR-delta agonists such as GW501516 induce upregulation in skeletal muscle fatty acid oxidation and produce beneficial changes in high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein A1, and apolipoprotein B toward a less atherogenic profile.[181]

Other LDL-lowering therapies

Bempedoic acid and inclisiran are newer nonstatin therapies approved for use with diet and maximally tolerated statin therapy in adults who require additional lowering of LDL-C.[182] Trials assessing clinical outcomes are ongoing. In the CLEAR Outcomes trial, statin-intolerant patients receiving bempedoic acid had a 21.7% reduction in LDL-C at 6 months, compared with 0.6% reduction with placebo, and also had a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization).[183][184]

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