Interesting modeling exercise. The attenuated weight loss in T2D is real and clinically important. However, framing the explanation primarily in terms of changes in energy expenditure and the caloric equivalent of urinary glucose excretion keeps the analysis inside the same energy-balance framework whose limitations have been repeatedly noted (e.g., 1,2,3).

Urinary glucose excretion is first and foremost a mass outflow (grams of glucose leaving the system). Treating it principally as an “energy sink” converts a direct mass loss into an indirect energetic term and then uses that term to explain a mass (weight) outcome. A mass-balance perspective would track the grams of glucose excreted alongside other mass flows without the intermediate conversion, thereby avoiding the additional assumptions required by energy-density estimates.

The observation that background SGLT2i therapy further attenuates weight loss is consistent with a larger baseline mass outflow that diminishes as glycemia improves. This can be stated directly in mass units. Whether the same phenomenon is best understood as a change in energy gap or as a change in net mass balance remains an open and consequential question.

References 1. Manninen AH. Mass Balance over Energy Balance: Why Direct Mass Accounting Offers a More Precise and Mechanistically Faithful Framework for Human Body Weight Regulation. Preprints 2026, 2026040690. https://doi.org/10.20944/preprints202604.0690.v4 2. Manninen AH. Implementing the Mass Balance Model (MBM) in Human Nutrition and Obesity Research: Protocols, Analytical Frameworks, and Translational Applications. Preprints 2026, 2026041641. https://doi.org/10.20944/preprints202604.1641.v2 3. Arencibia-Albite F. A numerical and analytical evaluation of the consistency of the energy balance model identifies limitations and systematic relationships between mass intake and body weight dynamics. Front Nutr. 2026 Jul 30;13:1777554. doi: 10.3389/fnut.2026.1777554. PMID: 42597285; PMCID: PMC13468908.