Tirzepatide vs Semaglutide Linked to Lower Metabolic Syndrome Prevalence – Renal and Urology News

Use of tirzepatide, compared with placebo, semaglutide, and insulin degludec and glargine, is associated with a lower prevalence of metabolic syndrome among patients with type 2 diabetes, according to results of a post hoc analysis published in Cardiovascular Diabetology.

In the SURPASS clinical trial program (SURPASS 1-5; ClinicalTrials.gov; Identifiers: NCT03954834, NCT03987919, NCT03882970, NCT03730662, NCT04039503), the effect of tirzepatide for reducing glycated hemoglobin (HbA_1c) and body weight among patients with type 2 diabetes was evaluated. Compared with placebo, semaglutide 1 mg, and insulin degludec and glargine, tirzepatide was associated with greater improvements in body weight reduction and glycemic control.

To assess the effect of tirzepatide on metabolic syndrome prevalence, researchers conducted a post hoc analysis of SURPASS 1-5. Adults with type 2 diabetes (N=5219) were randomly assigned to receive 5 mg tirzepatide (n=1206); 10 mg tirzepatide (n=1162); 15 mg tirzepatide (n=1046); or placebo, 1 mg semaglutide, insulin glargine, or insulin degludec (n=1805) for 40 to 104 weeks.

The primary outcome was the prevalence of metabolic syndrome at follow-up, defined as meeting at least 3 criteria according to the United States National Cholesterol Education Program: Adult Treatment Panel III. The researchers also performed subgroup analyses according to categorical weight loss.

At baseline, 78% of patients had metabolic syndrome. The prevalence of metabolic syndrome decreased from 67%-88% at baseline to 38%-64% at weeks 40/52 among the tirzepatide group vs 77%-84% at baseline to 64%-82% at weeks 40/52 among the comparator groups (all P <.001).

Stratified by components of metabolic syndrome, data revealed that the proportion of tirzepatide vs comparator recipients who met a metabolic syndrome criterion decreased from baseline (maximum across all 5 trials) to follow-up (minimum across all 5 trials) for:

• Waist circumference (87.6% to 45.6% vs 84.3% to 64.2%);
• Fasting serum glucose or HbA_1c (100% to 55.1% vs 100% to 86.5%);
• Blood pressure (74.3% to 28.0% vs 74.3% to 43.2%);
• Triglycerides (56.4% to 17.3% vs 55.8% to 38.9%); and,
• High density lipoprotein cholesterol (65.9% to 37.1% vs 58.5% to 40.7%).

The effects of tirzepatide on metabolic syndrome correlated with the amount of body weight reduction, as patients who lost more than 20% of their body weight had a decrease in metabolic syndrome prevalence from 80%-91% at baseline to 20%-28% at follow-up.

The researchers identified no associations between the effects of tirzepatide and background use of sodium-glucose co-transporter 2 inhibitors or sulfonylurea. No between-group differences were observed for men and women.

One study limitation is the lack of a plateau of body weight and HbA_1c changes at follow-up, indicating the need for increased study durations. Other study limitations include the exclusion of data on antihypertensive and lipid-modifying medications and the exclusion of separate waist circumference thresholds for Asian participants.

The researchers concluded that “treatment with tirzepatide resulted in clinically relevant reductions in the prevalence of patients meeting the criteria for metabolic syndrome across the SURPASS clinical trial program. Greater body weight reduction with tirzepatide was associated with greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome.”

Disclosures: This research was supported by Eli Lilly and Company. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Endocrinology Advisor