Preliminary Findings From a Prospective Cohort Study of Tirzepatide in Adults With Obesity and Heart Failure With Preserved Ejection Fraction: Longitudinal Effectiveness, Cardiometabolic Response, and Gastrointestinal Tolerability in Kazakhstan

Background: Evidence describing the longitudinal effectiveness and tolerability of tirzepatide in adults with obesity and heart failure with preserved ejection fraction (HFpEF) remains limited, particularly from prospective cohorts with repeated cardiometabolic assessments. This study evaluated longitudinal changes in weight, metabolic health, and treatment-emergent symptoms during tirzepatide therapy in a Kazakhstan cohort with obesity and HFpEF.
Methods: We conducted a preliminary analysis of the tirzepatide-treated cohort enrolled at one center within a broader prospective interventional study. The present analysis included adults with obesity and HFpEF who received once-weekly tirzepatide according to a prospectively defined treatment protocol. Participants underwent scheduled assessments from baseline through Week 41. Longitudinal changes in anthropometric, metabolic, inflammatory, renal, and body composition outcomes were analyzed using linear mixed-effects models. Individual treatment-emergent symptoms were summarized descriptively, while longitudinal regression models were used for aggregated adverse-event outcomes and symptom burden. Complete-case and exploratory predictor analyses were performed as sensitivity analyses.
Results: Twenty-four participants with obesity and HFpEF contributed longitudinal observations, including 16 with mature Week-41 follow-up. Tirzepatide treatment was associated with significant reductions in body weight, BMI, waist circumference, fasting glucose, triglycerides, and selected inflammatory markers over time. Mean percentage weight loss at Week 41 was 17.2±8.1%, corresponding to 18.7±7.0 kg. Among the 16 participants with paired baseline and Week-41 measurements, all achieved ≥5% weight loss, while 87.5%, 50.0%, and 25.0% achieved ≥10%, ≥15%, and ≥20% weight loss, respectively. Gastrointestinal symptoms were reported in 25.0% of participants, with nausea (20.8%) and vomiting (12.5%) being the most frequently recorded. No serious adverse events were observed during the study period. No statistically significant association was detected between gastrointestinal symptom occurrence or burden and longitudinal weight loss; however, these analyses were exploratory given the small number of gastrointestinal events.
Conclusions: In this preliminary analysis of a prospective tirzepatide-treated cohort of adults with obesity and HFpEF from Kazakhstan, tirzepatide was associated with substantial and sustained weight loss accompanied by favorable cardiometabolic changes. Gastrointestinal symptoms were reported in a minority of participants, although their severity was not formally graded. These findings should be interpreted within the specific clinical context of obesity with concomitant HFpEF.