All worked; the 5:2 plan (two low-calorie days per week) was the easiest to stick to—and delivered the strongest metabolic gains.
A randomized clinical trial unveiled at ENDO 2025 directly compared three popular dietary strategies for people with obesity and type 2 diabetes: 5:2 intermittent energy restriction (IER), a 10-hour time-restricted eating window (TRE), and continuous energy restriction (CER). The takeaway: all three improved weight and blood sugar, but 5:2 was the easiest to sustain and produced larger gains in fasting glucose, insulin sensitivity (Matsuda index), and triglycerides.
Trial snapshot
Led by Haohao Zhang, Ph.D., from the First Affiliated Hospital of Zhengzhou University (China), this single-center, randomized, parallel-controlled trial ran from November 19, 2021, to November 7, 2024. Ninety adults enrolled (mean age 36.8 years; diabetes duration 1.5 years; BMI 31.7 kg/m²; HbA1c 7.42%). Sixty-three completed the 16-week, nutritionist-supervised intervention, with matched weekly caloric intake across all groups.
What changed—and for whom
Although HbA1c and weight loss did not differ significantly between groups, the largest absolute reductions occurred in the 5:2 arm. Compared with TRE and CER, 5:2 also lowered fasting glucose more, boosted whole-body insulin sensitivity, and reduced triglycerides more strongly. Uric acid and liver enzymes showed no significant changes in any arm.
Mild hypoglycemia occurred in two participants in IER, two in TRE, and three in CER.
Adherence: the tiebreaker
Adherence was highest with 5:2 (85%), followed by CER (84%) and TRE (78%). IER and CER significantly outperformed TRE. In practice, the best diet is the one patients can actually follow—and here, that was 5:2.
Why did the “easiest” win?
The 5:2 pattern compresses aggressive calorie restriction into just two days per week, allowing five normocaloric days. That behavioral and social simplicity likely explains its better adherence—and superior metabolic readouts.
Clinical implications
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All three approaches are valid and confer benefits.
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If targeting fasting glucose, triglycerides, and insulin sensitivity, 5:2 stands out from this head-to-head trial.
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Personalize the plan: medications (hypoglycemia risk), lifestyle, comorbidities, and patient preference should drive the choice.
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Close monitoring (especially with insulin or sulfonylureas) is crucial early on to adjust doses and prevent hypoglycemia.
Bottom line: All three roads help, but if you want results patients can realistically sustain, 5:2 deserves to be first on the table.
Source: Endocrine Society
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