Type 2 Diabetes Remission: A Systematic Review and Meta-analysis of Nonsurgical Randomized Controlled Trials

Abstract

Background: Evidence that type 2 diabetes can be reversed has been limited by the understanding and implementation of these interventions.

Purpose: We assessed the effect of nonsurgical randomized controlled trials (RCTs) on type 2 diabetes remission and characterized core components.

Data sources: We reviewed articles from MEDLINE and Embase (inception to April 2025).

Study selection: RCTs of multimodal pharmacological or nonpharmacological type 2 diabetes remission interventions for adults with type 2 diabetes were included.

Data extraction: Study characteristics and outcomes for clinical/population health, patient-reported, and adverse event were extracted.

Data synthesis: We performed a random-effects multilevel meta-analysis of studies, grouped based on type of intervention and by length of follow-up. A total of 18 studies were included in this review from 11 different countries. There was a higher likelihood of achieving type 2 diabetes remission through multimodal interventions (risk ratio [RR] 1.75 [95% CI 1.49-2.04]) and for nonpharmacological interventions (RR 5.80 [95% CI 4.28-7.87]), compared with the control group. Other significant outcomes for intervention groups compared with control groups included change in A1C, weight loss, and quality of life and improvements in adverse events of hypoglycemia.

Limitations: There was heterogeneity in our small pool of included studies (diversity of nonpharmacological components), stringent intervention protocols, narrow participant selection criteria, and lack of consistent diabetes remission definitions.

Conclusions: With specific protocols, a variety of tailored approaches can induce type 2 diabetes remission for patients with newly diagnosed type 2 diabetes who are able to subscribe to strict protocols. Consideration of long-term sustainability and effectiveness is needed in future research, along with patient preferences.

Graphical abstract

Figure 1

PRISMA 2020 flow diagram for new systematic reviews, including searches of databases, registers, and other sources. Adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. For more information, visit https://www.prisma-statement.org/.

Figure 2

The effect of multimodal pharmacological (A) and nonpharmacological (B) interventions on type 2 diabetes remission (any definition). Intervention and control columns denote the number of remission events per total group participants. Immediate post, immediately postintervention.

Figure 3

A and B: The effect of multimodal pharmacological and nonpharmacological interventions on weight loss as percent body weight loss (A) or change from baseline (kilograms) (B). Weight change in kilograms was not presented for pharmacological interventions, and weight loss as percent body weight was only reported from two studies with nonpharmacological interventions. C and D: The effect of nonpharmacological interventions on A1C, postintervention (C), and as change from baseline (D). A1C results from pharmacological interventions were nonsignificant. MD, mean difference.