Global and regional level association between depression and glycemic control in type 2 diabetes mellitus: A systematic review and meta-analysis

Background: Depression and type 2 diabetes mellitus (T2DM) are major global public health concerns. Depression worsens glycemic control through behavioral and biological pathways, increasing insulin resistance and poor adherence to diabetes care. Aim: This systematic review and meta-analysis (SRMA) examined the association between depression and glycemic control among individuals with T2DM worldwide. Materials and Methods: Following PRISMA guidelines, studies published from January 2000 to May 2024 were retrieved from Cochrane, Embase, ProQuest, Web of Science, and PubMed. Thirty-eight studies were included to assess mean differences (MDs) in HbA1c and fasting blood sugar (FBS), proportions with poor glycemic control, and medication adherence among those with and without depression. Random-effects models in R Studio were used, with subgroup and meta-regression analyses addressing heterogeneity. Results: Depressed individuals showed a significant mean increase of 0.30% in HbA1c compared to nondepressed counterparts (95% CI: 0.09-0.51; n = 20). Stronger associations were observed in North American studies, larger sample sizes, and those using Patient Health Questionnaire-9 (PHQ-9) cutoff scores >10. Duration of diabetes significantly influenced the HbA1c difference. No significant association was found for poor glycemic control (OR = 1.74, 95% CI: 0.81-3.73; n = 12), FBS (MD = 24.39, 95% CI: -17.29-66.06; n = 4), or medication adherence (OR = 1.86, 95% CI: 0.57-6.10; n = 5). High heterogeneity (I² > 90%) and publication bias were noted, with GRADE rating the evidence as very low certainty. Conclusion: Depression modestly affects glycemic outcomes in T2DM, with heterogeneity among studies. Higher HbA1c among depressed patients was found with low certainty and to be minimally clinically significant. Methodologies in the included studies emphasize the need for standard approaches and better study designs (prospective cohort studies). Prospero registration number: CRD42024543104, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024543104.