Diabetes mellitus is one of the major public health problems that requires appropriate self-care practices to reduce complications. The current study assessed adherence to self-care practices and associated factors using the theory of planned behavior and the health belief model among type 2 diabetes mellitus patients. A facility-based, sequential explanatory mixed-method was undertaken at comprehensive specialized hospitals in the Amhara region of Ethiopia. A single population proportion formula was used to calculate sample size. Proportional allocation to the three study settings and systematic random sampling techniques were used to select 846 study participants. Logistic regression analysis was used to identify associated factors. Variables with a P-value less than 0.05 were declared statistically significant. For the qualitative study, purposive sampling was used to select sixteen key informants, and thematic analysis was performed. About 42.4% of the study participants had good adherence to self-care practices. Being a member of a diabetes association (AOR = 2.57, 95% CI: 1.51, 4.38), having a home glucometer (AOR = 2.52, 95% CI: 1.59, 4.02), having good glycemic control (AOR = 4.07, 95% CI: 2.53, 6.53), having low perceived barriers (AOR = 8.65, 95% CI: 4.65, 16.07), and having middle perceived barriers (AOR = 3.26, 95% CI: 1.88, 5.66) were significantly associated with good adherence to self-care practice. On the other hand, poor wealth index (AOR = 0.27, 95% CI: 0.16, 0.46), poor behavioral control (AOR = 0.59, 95% CI: 0.36, 0.97), poor behavioral intention (AOR = 0.36, 95% CI: 0.21, 0.64), low perceived benefits (AOR = 0.20, 95% CI: 0.08, 0.51), and middle perceived benefits (AOR = 0.57, 95% CI: 0.31, 0.83) were significantly associated with poor adherence to self-care practice. The key informants explored the influence of patients' beliefs, self-efficacy, social support, and barriers on their self-care practices. Less than half of type 2 diabetes mellitus patients had good adherence to self-care practices. This was more evident for patients who are members of a diabetes association, having a high wealth index, having a home glucometer, good behavioral control, good behavioral intentions, high perceived benefit, and poor perceived barriers. Appropriate intervention should be designed based on the aforementioned factors.
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