Weight Loss Improves Cardiometabolic Biomarkers in Digital Metabolic Reset Program

Patients achieving significant weight loss in a digital metabolic reset program can also substantially improve key cardiometabolic markers, according to recent data.¹

With the advent of GLP-1 receptor agonists (RAs) and similar incretin-based therapies, weight loss has transformed from a gradual process to an achievable endpoint through medical therapy. Drugs such as semaglutide and tirzepatide have dominated obesity treatment, while investigative therapies like retatrutide have demonstrated weight loss exceeding that of bariatric surgery during clinical trials. In light of this rapidly expanding approach to 1 of the most prolific diseases in the US, clinicians have taken an increasing interest in alternative effects of these revolutionary therapies.²

Presented at the Endocrine Society (ENDO) Annual Meeting 2026 in Chicago, Illinois, by Christine May, PhD, of Calibrate Health, this study addresses what May and colleagues believe to be a significant gap in cardiometabolic health improvements during weight loss. Given its status as the primary goal in most obesity management trials, weight loss can frequently overshadow meaningful improvements in key biomarkers including HbA1c, lipid profiles, and liver function tests (LFTs). All of these are contained within a digital metabolic reset program.¹

“We hypothesized that participants would demonstrate high rates of cardiometabolic normalization in addition to weight loss,” May and colleagues wrote. “We also examined the association between program engagement and these outcomes.”¹

May and colleagues conducted a longitudinal analysis on patients who were enrolled in a comprehensive digital health program, which combined intensive lifestyle interventions with GLP-1 pharmacotherapy. A total of 1921 patients were included, of whom 81.1% were female, 78.3% were White, and 73.3% were aged ≥46 years. May and colleagues assessed key cardiometabolic biomarkers, such as percent total body weight lost (%TBWL), HbA1c, lipid panels, and LFTs, at baseline and 24 months.¹

The team employed regression models to determine the association between program engagement and the above outcomes. Engagement was defined as a composite score of coaching attendance and personal logging: the latter, in turn, included high-calorie/low-nutrient-density foods, sleep, and self-reported energy levels. Both factors were categorized from low to high.¹

May and colleagues noted that participants achieved a mean %TBWL of 19.1%, with 77% normalizing ≥1 cardiometabolic marker by 24 months. Among those with abnormal baseline HbA1c (≥5.7%), roughly 81% achieved normalization within 24 months. Additionally, 91% of participants achieved normalization of AST, while 84% achieved normalized ALT. All other biomarkers normalized in significant proportions of participants (64-78%), with the exception of LDL cholesterol (24%).¹

Regression analysis also demonstrated that patients with high engagement achieved substantially greater %TBWL and improvements in insulin levels and HbA1c versus those with low engagement (P <.05). Despite this, no significant differences were observed across engagement groups for other biomarkers.¹

Ultimately, May and colleagues determined that these data indicate the potential for substantial improvements in key cardiometabolic markers alongside weight loss.¹

“High rates of biomarker normalization underscore the potential of a multi-pillar approach that combines GLP-1 pharmacotherapy with intensive lifestyle intervention,” May and colleagues wrote. “These results also suggest that higher program engagement may enhance weight loss and improvements in HbA1c and insulin levels at 24 months.”¹

References

1. May C, Khuen V, Williams K, et al. Weight Loss and Improvements in Cardiometabolic Markers: A 24-Month Longitudinal Analysis of a Digital Metabolic Reset Program. Abstract presented at the Endocrine Society (ENDO) Annual Meeting 2026, Chicago, IL. June 13-15, 2026.

2. Chao AM, Tronieri JS, Amaro A, Wadden TA. Semaglutide for the treatment of obesity. Trends Cardiovasc Med. 2023;33(3):159-166. doi:10.1016/j.tcm.2021.12.008