JAMA Network Open recently published results of a randomized, open-label, active parallel-controlled clinical trial comparing an intermittent fasting program to both metformin and empagliflozin in Chinese adults with early type 2 diabetes. Known as the EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study, 405 participants were randomized in a 1:1:1 ratio to either metformin, empagliflozin, or the 5:2 MR, the latter consisting of 2 non-consecutive fasting days and 5 days of usual intake per week and meal replacement (MR) diet. Participants following the 5:2 MR had, within 1 week, 5 days of consuming their usual breakfast and lunch but a meal replacement for dinner, and on the 2 non-consecutive days, only consumed 1 meal replacement for a daily energy intake of 500 kcal for women and 600 kcal for men (on those 2 days). The 2 meal replacement formulations provided 17-20g of protein per serving, with ingredients including medium chain triglycerides, DHA, extra-virgin olive oil, etc.
The study was 16 weeks long with 8 weeks of additional follow-up; hemoglobin A1c (HbA1c) was the primary endpoint. The 5:2 MR approach was found to be superior to either drug in terms of glycemic control and weight loss. The HbA1c was reduced by 1.9% in this group, a significantly greater increase than either medication (e.g. metformin -1.6% and empagliflozin -1.5%). The 5:2 MR program also resulted in more significant and sustained reductions in weight loss and waist circumference; a weight loss of −9.7 kg with 5:2 MR versus −5.5 kg and -5.8 kg in the medication groups. There were similar improvements in fasting glucose and insulin, C-peptide levels, and HOMA-IR between groups, but more favorable changes in blood pressure, triglycerides, and HDL-C in the 5:2 MR group.