OBJECTIVES:  In most patients with type 2 diabetes mellitus (T2DM), therapy starts with adjusting lifestyle and weight control. Evidence showed that newer anti-diabetic therapy, such as incretin peptides (e.g. GLP-1 RAs), can regulate body weight. This study examined the evidence on the impact of weight loss in people with T2DM and its consequences on endpoints measured by Patient-Reported Outcomes (PROs), such as health-related quality-of-life (HRQOL). METHODS: A systematic literature review was carried out with two independent reviewers to collect clinical trial and real-world evidence regarding the effects of weight loss on PRO results. Data sources included Embase, Medline and Cochrane without time limitation. Additionally, conference proceedings were searched (2013-2015). RESULTS:  The review identified 20 relevant RCTs and observational studies reporting 23 associations between weight loss and PROs. These studies described associations/correlations via Spearman or Pearson regression coefficients, logistic regression analysis or odds ratio. Twenty-one associations described a positive correlation (implying a beneficial effect of weight loss on PRO results), on two occasions no relationship was found. Most commonly reported PRO measure was the Impact of Weight on Quality of Life(-Lite) (IWQOL) with scales in physical function, self-esteem, sexual life, public distress, and work. All 7 studies showed a positive association between weight loss and IWQOL scores. For the Medical Outcomes Survey, Short Form 36 (SF-36); 5 of the 7 studies observed a beneficial association between weight loss and HRQOL. Additionally, positive associations were found between weight loss and PROs for depression (2 studies), health satisfaction (2), treatment satisfaction (1), activities of daily living or well-being (2) and diabetes specific questionnaires (2). CONCLUSIONS:  Almost all studies observed a positive (i.e. beneficial) correlation between weight loss and PRO results in patients with T2DM. Overall, identified studies suggest that weight loss has a beneficial effect on HRQOL, depression, health satisfaction, and treatment satisfaction.