Background: To evaluate changes in cardiometabolic parameters by the degree of weight reduction maintenance with tirzepatide (TZP) treatment at a reduced dose of 5mg from maximum tolerated dose (MTD) vs placebo.
Methods: Participants received TZP at MTD for 60-weeks, then randomized to: TZP at MTD, at 5mg, or placebo for another 52-weeks (week 60-112). For 5mg TZP, the association between degree of weight reduction maintenance from week-60 to -112 and changes in markers of cardiometabolic health was assessed. Percent maintenance was calculated as percent change in weight (Week 0-112)/ change in weight (Week 0-60). Percent maintenance was divided into 4 categories: ≥100% (further weight reduction), 75-100%, 50-75%, and <50%. Changes from baseline to week-60 and to week-112 in blood pressure, lipids, HbA1c, waist circumference, fasting insulin were summarized. For participants regaining ≥50% of lost weight by Week-84/ later receiving ‘rescue TZP’, the worst observed values prior to rescue were imputed.
Results: A total of 69 of the 132 TZP-treated participants that were randomized to 5mg dose maintained at least 75% of their initial weight reduction at Week-60. This group included numerically more women, White race, and older individuals. Across all 4 maintenance categories, improved cardiometabolic parameters during the first 60-weeks were mostly sustained at Week-112 in the >100% and 75-100% weight maintenance groups.
Conclusion: Over half maintained at least 75% of lost weight and sustained cardiometabolic benefits, including improved waist circumference, blood pressure, lipids, and HbA1c over one year in reduced TZP group. Groups with lesser degrees of weight maintenance had greater reversal of cardiometabolic improvements, underscoring the association between sustained weight loss and cardiometabolic benefit. Additional studies are warranted to better understand which patients may benefit from sustained vs lower doses of tirzepatide to maintain the weight reduction and associated cardiometabolic benefits.