Primary Care-Linked Lifestyle Interventions for Type 2 Diabetes Mellitus Remission and Glucose-Lowering Medication...

Type 2 diabetes mellitus (T2DM) is a common chronic disease that affects millions of adults around the world. Primary care-linked lifestyle interventions offer a scalable pathway to remission. However, evidence has not been synthesized with glucose-lowering medication deintensification as a co-primary outcome or with systematic separation of randomized, proof-of-concept, and real-world implementation evidence. We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL)) were searched in June 2026. Eligible studies included adults with T2DM enrolled in primary care-linked lifestyle interventions. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Quasi-Experimental Studies, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Pooled risk ratios (RRs) and mean differences were estimated using DerSimonian-Laird random-effects models. Six studies met eligibility criteria, including two primary 12-month randomized controlled trials (RCTs) and four additional proof-of-concept or implementation evidence streams. The two 12-month comparative RCTs (Diabetes Remission Clinical Trial (DiRECT) and Diabetes Intervention Acceleration through Mobilization I (DIADEM-I)) demonstrated a pooled remission RR of 7.42 (95% confidence interval (CI) 3.51-15.69; I² = 53%; moderate certainty) and medication-free status RR of 4.31 (95% CI 3.24-5.72; I² = 0%; moderate certainty). The pooled unadjusted mean difference in weight change was -8.75 kg (95% CI -10.01 to -7.48; I² = 0%), and the pooled mean difference in glycated hemoglobin change was -8.74 mmol/mol (95% CI -13.58 to -3.90; I² = 70%; low certainty). Single-arm and real-world implementation evidence showed a pooled remission proportion of 42.6% (95% CI 26.4-59.6%; I² = 95%; very low certainty), interpreted as implementation rates rather than causal treatment effects. Primary care-linked lifestyle interventions, particularly total diet replacement-based pathways, substantially increase the likelihood of T2DM remission and medication-free status at 12 months. Sustained weight loss appears to be the primary mediating mechanism. Safe implementation requires structured medication withdrawal protocols and long-term primary care follow-up.