PHARMACOLOGICAL INTERVENTIONS EFFECT FOR DEPRESSION IN GLYCEMIC CONTROL AND WEIGHT VARIATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Resumo

Introduction: The coexistence of type 2 diabetes mellitus (T2DM) and major depressive disorder has become an increasingly common reality worldwide. This raises concern, as evidence indicates that this mood disorder tends to be more persistent and recurrent in this patient profile, in addition to feeding back into the pathophysiology of the endocrine disorder itself. This occ urs because of inadequate diet, low levels of physical activity, and poor medication adherence, which are factors that are very common among patients with depression, further exacerbate insulin resistance. In this context, pharmacological approaches to depression are promising and emerge as an important pillar in the treatment of this metabolic disease, contributing to glycemic and weight control within the specific targets for this population. Objective: To evaluate the effect of pharmacological interventions with selective serotonin reuptake inhibitors (SSRIs) and serotonin -norepinephrine reuptake inhibitors (SNRIs) on glycemic control, assessed through glycated hemoglobin (HbA1c), and on body weight variation in patients with T2DM, whether receiving diabetes treatment or not. Methods: A systematic review was conducted in accordance with the PRISMA guidelines, aiming to answer the following question: “In patients with type 2 diabetes mellitus, do interventions for depression improve glycemic control and wei ght change compared with usual care?”, developed based on the PICO(T) acronym. The search was performed in the PubMed and Cochrane Library databases using the descriptors “Diabetes Mellitus, Type 2” AND “Antidepressive Agents” AND “Glycemic Control”. The i nclusion criteria comprised randomized clinical trials, observational cohort studies, multicenter studies, and systematic reviews published in English within the last 10 years, while the exclusion criteria comprised other study designs. A total of 10 studi es were selected. Results: The analyzed studies demonstrated heterogeneous results regarding the efficacy of antidepressants on glycemic control in patients with T2DM. In a cohort analysis, a statistically significant association was observed when treatmen t duration extended up to 36 months after the diagnosis of T2DM, compared with the control group (HR 1.17; 95% CI 1.02 -1.34). However, although some studies suggest an association between antidepressant use and improved glycemic control, with reductions in HbA1c levels after the initiation of antidepressant therapy, most of them did not demonstrate consistent findings between exposed and unexposed groups, while some associated the use of multiple subclasses of antidepressants with higher HbA1c levels. Furthermore, findings related to weight loss outcomes were divergent with the administration of SSRIs or SNRIs in patients undergoing diabetes treatment. Initial weight loss was observed during the first months, followed by subsequent weight regain at 12 months . All SNRI users presented greater weight reduction throughout follow -up, especially during the first 6 months. In contrast, antidepressant users with type 2 diabetes mellitus presented significantly higher BMI compared with non-users (31.2 kg/m² versus 30.1 kg/m²; p < 0.001). Conclusion: Antidepressants, especially SSRIs and SNRIs, may benefit patients with T2DM and depression, with possible effects on glycemic control and weight variation. However, the evidence remains limited, and further studies on differences between drug classes and their metabolic impacts are needed to assist in therapeutic decision-making for these patients.