5:2 intermittent fasting plan makes a difference in early type 2 diabetes

An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake and meal replacement diet (5:2 MR) helps keep a lid on blood sugar and promote weight loss in adults with overweight or obesity and early type 2 diabetes (T2D), according to the results of the open-label EARLY* study from China.

The primary endpoint of haemoglobin A1c (HbA_1c) level decreased to a greater extent following 16 weeks of 5:2 MR than after treatment with either metformin (mean change from baseline, −1.9 percent vs −1.6 percent; adjusted difference, −0.3 percent, 95 percent confidence interval [CI], −0.4 to −0.1) or empagliflozin (mean change from baseline, −1.9 percent vs −1.5 percent; adjusted difference, −0.4 percent, 95 percent CI, −0.6 to −0.2).  [JAMA Netw Open 2024;7:e2416786]

Significantly more participants in the 5:2 MR arm than in the metformin and empagliflozin arms achieved an HbA_1c level of <6.5 percent (80.0 percent vs 60.4 percent and 55.1 percent; p<0.001 for both comparisons), with 76.6 percent of participants in the 5:2 MR arm having their HbA_1c level maintained below 6.5 percent at the end of the 8-week post-treatment follow-up.

Furthermore, 5:2 MR led to a greater weight loss compared with metformin and empagliflozin (mean change from baseline to week 16, −9.7 vs −5.5 and −5.8 kg, respectively). Participants in the 5:2 MR arm also showed substantial reductions in waist and hip circumference as well as systolic and diastolic blood pressure but no notable differences in most metabolic markers, except for triglyceride and high-density lipoprotein cholesterol.

As for the safety of 5:2 MR, eight patients experienced hypoglycaemia and one had constipation. While the incidence of hypoglycaemia was comparable across the three treatment arms, the investigators stressed the importance of preventing hypoglycaemic events associated with low-energy diet when implementing 5:2 MR.

“A 5:2 MR plan may reshape the gut microbiota, promote white adipose tissue browning, and consequently reduce insulin resistance and the occurrence of obesity. The MR used in this study contained omega-3 fatty acids and medium-chain fatty acids,” the investigators said. [Cell Metab 2017;26:672-685; Hepatobiliary Surg Nutr 2020;9:597-602]

“Omega-3 fatty acids regulate leptin, inhibit fat synthesis, and promote fat breakdown. Meanwhile, medium-chain fatty acids reduce heterotopic fat, enhance brown fat thermogenesis, and increase insulin sensitivity,” they continued. [Nutrients 2017;9:573; Front Nutr 2022;9:896021]

The findings of the EARLY study suggest that 5:2 MR may serve as an effective initial lifestyle intervention instead of glucose-lowering drugs for early-stage T2DM, according to the investigators. This supports the 2020 Chinese Diabetes Society Guidelines, which emphasize lifestyle intervention as the foundational treatment for T2D, with medication initiated only if lifestyle intervention fails to improve glycaemic control, they added. [Chin J Diabetes Mellitus 2021;13:315-409]

EARLY included 405 adults with T2D (mean age 45.5 years, 65.4 male) with a mean BMI of 29.5 kg/m² and mean HbA_1c level of 7.9 percent at baseline. These participants were randomly allocated to the 5:2 MR arm (n=135), metformin arm (n=134), or empagliflozin arm (n=136). A total of 332 participants completed the 16-week treatment, for a completion rate of 82.0 percent.

Metformin was given at 0.5 g twice daily and escalated to 2 g per day if the initial dose was tolerated. Empagliflozin was administered at 10 mg once daily. In the 5:2 MR arm, on the 2 nonconsecutive days on which meals are replaced, participants were required to consume 1 serving of Kang zhijun A instead of all 3 regular meals, with a daily energy intake of 500 kcal for women and 600 kcal for men. On the remaining 5 days, participants chose their own breakfast and lunch but had 1 serving of Kang zhijun B for dinner and were encouraged to monitor their calorie intake. Dietary intake was recorded in a diary.

“Long-term follow-up studies to assess the durability of the effects of 5:2 MR are underway,” the investigators said.

* Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus