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2:5 Intermittent Energy Restriction Diet Beneficial for Patients with T2D

by Lewis Chang, PhD

Intermittent Energy Restriction (IER) vs. Continuous Energy Restriction (CER)

Excess energy intake over time contributes to weight gain and the obesity epidemic; therefore, restricting food intake is essential in weight management. Although cutting calories daily can be successful for short-term weight loss, the majority of individuals regain their lost weight in the long term as a result of compensatory physiological adaptations. For example, resting energy expenditure (REE)—the minimum energy needed to maintain vital physiological functions such as heartbeat and breathing, which accounts for roughly >60% of total energy expenditure in humans—drops disproportionally following weight loss, thus significantly reducing the efficacy of the original weight loss regimen.1 Also, changes in hormones in the body after the initial weight loss mostly favor weight regain by increasing appetite and hunger level and promoting energy storage.2

To help ease difficulties in adhering to the conventional dieting approach, or continuous energy restriction (CER), scientists have been studying other dietary approaches that may be more practical. One promising method is termed intermittent energy restriction (IER): periods of marked energy restriction interspersed with normal energy intake from habitual diet. Various ways of practicing IER exist, such as the 2:5 IER (2 days/week of 60-75% energy reduction and 5 days/week of habitual diet) or the alternate-day energy restriction (60-70% energy reduction every other day).

Data from clinical trials of IER, particularly long-term ones, are still limited. A recent meta-analysis based on 6 published trials (the duration of studies ranged from 3 to 12 months) found that IER was as effective as the conventional CER in terms of total weight loss.3 There are other favorable results as well. One analysis of 2 trials (4 months and 6 months in duration, respectively) found that not only was 2:5 IER easier to adhere to than CER, IER also led to spontaneous reduced energy intake of approximately 20% during non-dieting days and no compensatory overeating occurred.4

IER vs. CER in Individuals with Type 2 Diabetes (T2D)

For individuals who are overweight or obese and also affected by type 2 diabetes (T2D), long-term weight loss is important in improving glucose, lipids, and blood pressure.5 However, a systematic review based on T2D weight loss trials found that the majority of trials did not achieve the clinically beneficial 5% weight loss at 12 months.6  Since IER has been shown to be easier to comply to than CER in individuals with overweight or obesity,4 can IER also help increase dietary compliance in patients with T2D and achieve better weight loss and glycemic control?

The first randomized clinical trial comparing the effect of 2:5 IER vs. CER in patients with T2D was published in JAMA Network Open.7 In this 12-month study, 137 patients with T2D were randomized to (a) an IER diet consisting of 75% energy restriction (500-600 kcal/day) for 2 nonconsecutive days/week with 5 habitual diet days/week for 12 months, or (b) a CER diet consisting of 30% energy restriction (1200-1500 kcal/day) for 7 days/week for 12 months. Both IER and CER regimens had similar total calorie intake per week (11,500 kcal/week and 10,300 kcal/week, respectively). Outcomes such as body weight and HbA1c (biomarker of long-term glucose control) were measured at baseline, 3 months, and 12 months.

The study found that IER and CER were equally effective at reducing HbA1c levels, with a mean HbA1c change (mean ± SD) at 12 months of -0.3 ± 0.1% and -0.5 ± 0.2%, respectively.7 IER was as effective as CER in mean weight change at 12 months as well (-6.8 ± 0.8 kg and -5.0 ± 0.8 kg, respectively).7 There was an indication that IER might be superior to CER in weight reduction, but a study with a larger sample size would be required to statistically determine superiority. Anecdotally, the CER group found weight loss maintenance more difficult as daily energy restriction was required, whereas the IER group indicated that they could effectively prevent weight gain because energy restriction was required for 2 days. These data indicate that 2:5 IER is an effective alternative diet strategy for patients with T2D.7

T2D Medication Adjustment During IER

For patients with T2D, daily monitoring of fasting glucose levels is important. In the aforementioned 1-year trial, the IER group was requested to record additional glucose readings on the 2 energy restricting days to monitor hypoglycemia. The investigators found that the IER group required extra insulin reduction on the 2 energy restricting days to prevent hypoglycemic events.7 Therefore, patients with T2D should work closely with an endocrinologist during 2:5 IER to minimize risks of glycemic events and to ensure best of care. Further medication adjustments would also be needed as HbA1c and weight are improved.

In summary, although long-term data are still limited, the 2:5 IER may be a valuable, more practical, dietary approach than CER for weight loss and glycemic control for patients with T2D. During the initial stage of the IER, patients should work closely with an endocrinologist and make necessary individualized reductions to medications during the energy restricting days and in response to improvements in weight and HbA1c.


  1. Ebbeling CB et al. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA. 2012;307(24):2627-2634.
  2. Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes (Lond). 2015;39(8):1188-1196.
  3. Harris L et al. Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database System Rev Implement Rep. 2018;16(2):507-547.
  4. Harvey J et al. Intermittent energy restriction for weight loss: Spontaneous reduction of energy intake on unrestricted days. Food Sci Nutr. 2018;6(3):674-680.
  5. Evert ABet al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2013;36(11):3821-3842.
  6. Franz MJ et al. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. J Acad Nutr Diet. 2015;115(9):1447-1463.
  7. Carter S et al. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: A randomized noninferiority trial. JAMA Network Open. 2018;1(3):e180756.

Lewis Chang, PhD

Dr. Lewis Chang is Scientific Editorial Manager of R&D at Metagenics. Dr. Chang received his PhD in Nutritional Sciences at University of Washington, along with his MS in Nutrition and Public Health from Teachers College, Columbia University and BS in Pharmacy from National Taiwan University. Prior to joining Metagenics, he conducted dissertation research and completed a research assistantship and postdoctoral fellowship at the Fred Hutchinson Cancer Research Center in Seattle, WA. Dr. Chang has authored or co-authored and managed the publication of over 30 peer-reviewed journal articles and numerous scientific abstracts and posters. He has quite a green thumb, enjoys opera, theater and jazz, and loves cooking, collecting art, and learning to play gypsy jazz guitar.

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