Fasting plasma ghrelin concentrations are potential predictors of weight regain following diet-induced weight loss, according to study results published in Diabetes, Obesity and Metabolism.

One of the major obstacles in tackling obesity is the challenge of maintaining long-term weight loss. Previous studies have suggested a strong biological basis for weight regain after diet-induced weight loss. The objective of the current study was to assess whether appetite-related hormones (fasting leptin, ghrelin, glucagon-like peptide-1, peptide YY) may predict the risk for weight regain.

Data from the Diabetes Remission Clinical Trial (DiRECT), a cluster-randomized clinical trial aimed to determine the effect of weight loss on remission of type 2 diabetes, was used for the current post-hoc analysis. Intervention participants received a 24-month weight management program, and participants in the control group remained on usual diabetes care.

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The study sample included 253 patients (mean age, 53.6 years; 59% men), including 147 in the intervention group and 106 in the control group. Fasting plasma appetite-related hormones were measured at baseline, 12 months, and 24 months in all subjects, and at 5 months in a subset of 56 participants in the intervention group and in 22 participants in the control group. Multivariable linear regression models were used to identify potential predictors of weight regain.

At 5 months after the intervention, there was a 14.3% weight loss in the intervention group, but this reduction was followed by weight regain, with weight loss at 12 months of 10.1 kg (10.0%, P <.001), and a mean weight regain of 2.6 kg (3.1%, P <.001) between years 1 and 2. In the control group, participants lost on average 1.1 kg (1.1%, P =.003) at 12 months and 2.1 kg (2.1%, P <.001) at 24 months.

There was a 2.3% (95% confidence interval [CI], 0.4-4.1; P =.019) increase in body weight between 12 and 24 months for every 1-ng/mL increase in ghrelin between baseline and 12 months. Weight regain at 24 months increased by 1.1% (95% CI, 0.2-2.0; P =.023) body weight for every 1-ng/mL increase in ghrelin at 12 months.

For every 1-ng/mL increase in leptin levels between baseline and 12 months, body weight increased by 0.5% (95% CI, 0.140-0.835; P =.007) at 12 months. However, changes in leptin levels were not significant predictors of weight regain at 24 months.

Changes in concentration of GLP-1 and PYY between baseline and 12 months were not significant predictors of weight regain at 12 or 24 months.

The study had several limitations, including those associated with an exploratory analysis of a study that was not specifically designed to investigate the association between hormones and weight changes, and lack of data on other important hormones and pathways involved in weight loss maintenance. Additionally, biochemical measurements were undertaken using multiplex assays, which may provide less accurate and precise measurements.

Lastly, no postprandial samples were available and analyses were limited to fasting measurements.

“This study provides some further important evidence for the hypothesis that compensatory changes in appetite hormones contribute to weight regain following diet-induced weight loss. The rise in ghrelin that was observed in response to weight loss remained elevated over time and predicted weight regain during follow-up,” wrote the researchers.

Disclosures: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Thom G, McIntosh A, Messow CM, et al. Weight loss-induced increase in fasting ghrelin concentration is a predictor of weight regain: evidence from the Diabetes Remission Clinical Trial (DiRECT). Published online December 2, 2020. Diabetes Obes Metab. doi:10.1111/dom.14274