Intermittent Fasting: A Promising Treatment for Diabetes?

Lilian White, MD
Posted on July 15, 2024

Intermittent fasting has been studied with some promising results for the treatment of obesity. More generally, intermittent fasting refers to periods of caloric restriction and includes options such as alternate-day fasting and time-restricted feeding (e.g., eating only during a few specified hours of the day). Currently, the 2020-2025 U.S. Dietary guidelines do not make a recommendation regarding intermittent fasting for health benefits. Meal replacement (replacing one meal with a food or drink that has been prepackaged and often with less calories than a typical meal) has also been studied with some success for promoting weight loss.

A recent study published in JAMA evaluated the effectiveness of intermittent fasting combined with meal replacement for the treatment of type 2 diabetes mellitus compared with treatment with either metformin or empagliflozin alone. The randomized controlled trial evaluated the effect of a 16-week intermittent fasting protocol on 405 adults by evaluating the change in A1C levels. The intermittent fasting plus meal replacement plan comprised 5 days of usual food intake along with meal replacement with 2 nonconsecutive days of fasting (5:2 meal replacement). In this study, fasting was defined as 500 kcal for women and 600 kcal for men, which is about one-quarter the usual daily caloric intake. A prepackaged meal replacement was used on the fasting days to limit calories.

Patients treated with the 5:2 meal replacement plan showed the greatest reduction in A1C percentage (-1.9%) compared with baseline. This was statistically significant compared with the metformin and empagliflozin groups (-1.6, -1.5, respectively). No statistically significant difference occurred in A1C between the metformin and empagliflozin groups, which reaffirms the common use of metformin as an inexpensive, first-line pharmacologic option for the treatment of early type 2 diabetes. An A1C level of < 7% is considered a primary goal for the treatment of patients with diabetes to reduce the risk of long-term complications of the disease. A statistically significant number of the 5:2 meal replacement group was able to achieve an A1C level < 7% (and 6.5%) compared with the other two groups, providing support for 5:2 meal replacement as a clinically significant intervention.

Adverse effects with intermittent fasting are possible and occurred in 7% of participants in the 5:2 meal replacement group; they included constipation and hypoglycemia. This is lower when compared with 28% of the metformin group and 14% of the empagliflozin group who experienced adverse effects (including two patients with serious adverse events). The percentage of patients experiencing hypoglycemia was similar in the 5:2 meal replacement compared with the metformin group.

Overall, this study demonstrated that 5:2 meal replacement is a relatively safe intervention with a significant clinical potential for benefit, even more so than metformin and empagliflozin. However, as noted in a previous AFP Community Blog post on intermittent fasting, more research is needed. I’ll be curious to see future studies with larger numbers of patients and long-term follow-up or intervention. It will also be useful to better understand whether the quality or nutrition of the meal replacement is an essential factor or whether simply limiting calories is the key. In the meantime, the reassuring safety profile of 5:2 meal replacement makes it a promising option for the treatment of diabetes and highlights the continued value of diet and exercise for the management of patients with diabetes.