Introduction: Depression is a common and serious complication of diabetes. Treatment approaches addressing the specific demands of affected patients are scarce.

Objective: The aim of this work was to test whether a stepped care approach for patients with diabetes and depression and/or diabetes distress yields greater depression reduction than treatment-as-usual.

Methods: Two-hundred and sixty patients with diabetes and elevated depressive symptoms (CES-D ≥16) and/or elevated diabetes distress (PAID ≥40) were randomized to stepped care for depression or diabetes treatment-as-usual. The primary outcome was the rate of meaningful depression reduction at the 12-month follow-up according to the HAMD (score <9 or reduction by ≥50%). Secondary outcomes were changes in depression scores (HAMD/CES-D), diabetes distress (PAID), diabetes acceptance (AADQ), well-being (WHO-5), quality of life (EQ-5D/SF-36), self-care behavior (SDSCA/DSMQ), HbA1c, and biomarkers of inflammation.

Results: One-hundred and thirty-one individuals were assigned to stepped care and 129 to treatment-as-usual. Overall, 15.4% were lost to follow-up. Meaningful depression reduction was observed in 80.2 versus 51.2% in stepped care versus treatment-as-usual (p < 0.001, intention-to-treat analysis). Of the secondary measures, the HAMD (∆ –3.2, p < 0.001), WHO-5 (∆ 1.5, p = 0.007), and AADQ (∆ –1.0, p = 0.008) displayed significant treatment effects, while effects on CES-D (∆ –2.3, p = 0.065), PAID (∆ –3.5, p = 0.109), and SDSCA (∆ 0.20, p = 0.081) were not significantly different. Both groups showed comparable changes in EQ-5D/SF-36, DSMQ, HbA1c, and biomarkers of inflammation (all p ≥ 0.19).

Conclusions: The stepped care approach improved depression, well-being, and acceptance. The results support that increasing treatment intensity on demand is effective and can help provide more optimal treatment. The inclusion of diabetes-specific interventions may be beneficial for patients with diabetes and elevated depression.