Type 2 diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels in patients with impaired insulin secretion and insulin resistance.1,2 With an increasing prevalence worldwide, type 2 diabetes is a significant global health concern. It is projected that it will affect 11.3% of the adult population by 2030.3–5 In Portugal, the impact of type 2 diabetes is particularly noteworthy, with an estimated prevalence of 14.1% among individuals aged 20–79 years. Furthermore, the incidence of type 2 diabetes in Portugal is known to increase with age and body mass index (BMI).6

The development of type 2 diabetes is driven by a combination of lifestyle, environmental, and genetic factors; overweight/obesity and physical inactivity are the primary risk factors.3,7 Hence, effective management of type 2 diabetes patients aims to control blood glucose levels and improve patient quality of life through a multifaceted approach involving a healthy diet, regular physical activity, and pharmacological treatment.3,8,9 When uncontrolled or poorly managed, these patients are at an increased risk of developing diabetes-related micro- and macrovascular complications and morbidity, which may ultimately lead to patient death.10–12 Common complications and comorbidities associated with type 2 diabetes include hypertension, overweight/obesity, hyperlipidemia, chronic kidney disease (CKD), and cardiovascular (CV) disease.13 In fact, CV disease and type 2 diabetes are closely associated: individuals with type 2 diabetes are at higher risk of developing CV disease,14 which is the leading cause of mortality among type 2 diabetes patients.15,16 In addition, obesity, hypertension, and dyslipidemia are not only diabetes-associated comorbidities but also major risk factors for CV disease. Thus, the coexistence and interaction of both conditions coactively amplifies the risk of CV disease in type 2 diabetes patients.17

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) highlight that the pharmacological management of individuals with type 2 diabetes should be individualized, considering patient-specific characteristics and preferences, the influence of social determinants of health, disease duration, degree of hyperglycemia, presence or risk of diabetes-related comorbidities and complications, and the susceptibility to potential treatment side effects.18,19 However, the selection of appropriate antidiabetic agents is challenging, mainly because of their distinct efficacy, safety, and tolerability profiles.18,19 Moreover, type 2 diabetes patients often have a high prevalence of comorbidities, which rarely occur individually: up to 80% of type 2 diabetes patients may suffer from multimorbidity.20,21

In light of the challenges associated with type 2 diabetes management and the need for a comprehensive understanding of the Portuguese real-world scenario, the cMORE study was designed to evaluate the prevalence and co-prevalence of type 2 diabetes-related vascular complications and other comorbidities in patients attending primary healthcare services in Portugal. In addition, it aimed to assess the frequency of each type 2 diabetes-related condition based on the patients’ current antidiabetic treatment. The results of this study will raise awareness among healthcare professionals regarding the most common diabetes-associated complications/comorbidities affecting Portuguese type 2 diabetes patients and contribute to optimizing patient management and the efficient allocation of healthcare resources.

The cMORE study provides valuable insights into the sociodemographic and clinical characteristics, multimorbidity patterns, and pharmacologic management of patients with type 2 diabetes attending primary healthcare services in mainland Portugal. The findings of this study shed light on several important aspects of the disease, allowing for a comprehensive understanding of its complexity and the challenges associated with its management.

The sociodemographic and clinical characteristics of this sample are consistent with those of the primary care TEDDI study22 and of the overall Portuguese type 2 diabetes population, as reported in the Annual Report of the Portuguese Diabetes Society released in 2023.6 Patients were predominantly male and overweight, with a mean age of 67.7 years. The higher prevalence of type 2 diabetes in older individuals is in line with previous research13,23–25 and emphasizes the age-related risk factors associated with the disease, namely the co-prevalence of vascular complications and comorbidities.

This study examined the multimorbidity burden among type 2 diabetes patients and revealed a high prevalence of vascular complications and comorbidities. Overweight/obesity, dyslipidemia, and hypertension emerged as the most common type 2 diabetes-related conditions, and those with the highest co-prevalence, followed by the vascular complications micro- and macroalbuminuria, CKD, and CV diseases/procedures. This finding underscores the strong connection between type 2 diabetes and these conditions. In particular, there was a correlation between the duration of type 2 diabetes and diabetes-associated complications, namely CV disease/procedures. Concurrently, comorbidities such as dyslipidemia and hypertension were linked to the patient's age, thereby adding a layer of complexity to patient monitoring and treatment. Multimorbidity was present in the vast majority of patients and increased with age, BMI, and waist circumference. These findings are consistent with previous studies,13,24,26 although the prevalence of specific conditions may vary given the different sample characteristics, definitions of diabetes-related conditions evaluated, and type of data source.

Concerning vascular complications, the rates of micro- (38.1%) and macrovascular (19.6%) complications differ from other large multinational observational studies. The A1chieve27 (microvascular: 52.6%; macrovascular: 26.7%) and IMPROVE28 (microvascular: 45.0%; macrovascular: 28.0%) studies reported higher rates of vascular complications compared to the present study, whereas the DISCOVER study29 (microvascular: 18.8%; macrovascular: 12.7%) reported lower rates. While patients in these three studies were younger, had shorter disease duration, and higher HbA1c levels than the population in this study, the prevalence of vascular complications also differed between them. Nevertheless, in the A1chieve,27 DISCOVER,29 and cMORE, the likelihood of CV macrovascular complications was positively associated with similar variables, namely male sex and longer disease duration. Considering that intensive glycemic control has a beneficial effect on the incidence and progression of vascular complications,10–12,30 the observed differences between studies may result from different treatment approaches, patient adherence, or even access to treatment.

Most patients achieved the glycemic target of HbA1c <7%, as per the consensus guidelines of the ADA and EASD available at the time of patient enrolment,31–35 and in line with a previous study conducted in Portugal that showed good glycemic control (HbA1c <7%: 64.8%) in primary care patients.22 However, these guidelines also emphasize the importance of individualizing glycemic targets based on patient characteristics (e.g., age, social determinants of health, and disease duration), multimorbidity profile or risk of diabetes-related comorbidities and complications, and risk for adverse events to therapy (such as hypoglycemia), suggesting that less stringent HbA1c levels may be acceptable for certain patients.18,19,36,37 Given this sample's characteristics, where older patients had more multimorbidity and longer disease duration was associated with higher HbA1c levels,22 it is possible that more individuals achieved satisfactory glycemic control and appropriate disease management, justifying the acceptable rates of vascular complications. This assumption is further supported by the low frequency of type 2 diabetes patients with CV disease or requiring CV-associated procedures, despite the high incidence of major CV risk factors such as hypertension, obesity, and hyperlipidaemia.17 Still, the probability of having CV disease/procedures independently increased with longer disease duration, regardless of patient characteristics, accentuating the need for closer monitoring of patients who have lived with the disease for a long time (>10.5 years).

Glycemic control is not the only goal in the management of patients with type 2 diabetes. Clinicians also need to address the complications and comorbidities associated with diabetes, as these affect patients’ quality of life and potentially lead to anxiety and depression.18,38,39 In this context, selecting the most appropriate pharmacological treatment is a challenge, as it may adversely affect other existing conditions.18 Almost all patients of this study were prescribed glucose-lowering agents, with oral antidiabetics being the most frequent option. Among these, biguanides were the most common class and were most likely to be prescribed to patients initiating pharmacological treatment or achieving sustained glycemic targets.18,33 Insulin and GLP-1r agonists were used in a smaller subset of patients. The antidiabetic regimens varied according to the presence of complications and comorbidities, suggesting a personalized approach to treatment. Oral antidiabetics in combination with insulin were prescribed more frequently than oral agents alone for patients with hypertension, micro- or macroalbuminuria, CKD, CV disease/procedures, diabetic retinopathy, diabetic neuropathy, and diabetic foot infection. This implies that patients with more advanced disease may require intensified treatment regimens with insulin to achieve glycemic targets and delay the progression of additional vascular complications.10–12,30

Despite SGLT2i and GLP-1r agonists having a cardiorenal-protective role and being recommended for patients at high risk of or with established CV or renal diseases,18,31 their use in this study did not align with those recommendations. Indeed, the frequency of patients with CV disease or CKD who were receiving SGLT2i and biguanides dual therapy was similar to those receiving biguanides alone or combined with other oral agents. However, it is important to note that the guidelines with those recommendations were established shortly before the initiation of this study and their implementation can be a lengthy process, which may have been further delayed by the COVID-19 pandemic. Further evaluation is necessary to gain a deeper understanding of glucose-lowering prescription practices and whether they comply with current guidelines.

The cMORE study has several strengths, including its multicenter design and large number of enrolled patients, providing a representative sample of the mainland Portuguese scenario in terms of type 2 diabetes patient characteristics and prevalence of associated complications/comorbidities. Additionally, the study provides detailed associations between type 2 diabetes-related complications/comorbidities, highlighting patient characteristics that need to be considered in the Portuguese healthcare system when monitoring an individual with type 2 diabetes, and the use of antidiabetic agents.

However, there are some limitations to consider. Firstly, the COVID-19 pandemic affected the format of patient clinical appointments and data collection (e.g., anthropometric data). It also impacted the introduction and access to new glucose-lowering therapies. Secondly, the electronic case report form used in the study only allowed for six pre-defined options for CV disease/procedures, which may have affected the reporting of these parameters as patients with other CV problems were considered to have no CV disease or CV-related procedures. Finally, the cross-sectional nature of the study prevents the establishment of temporal relationships and inferences. A longitudinal analysis would provide evidence on whether patients are being properly managed at diagnosis of both the disease and associated complications/comorbidities. Also, evaluation of patient education about type 2 diabetes and lifestyle choices would offer valuable guidance on optimal strategies to implement throughout the course of the disease, in order to reduce the therapeutic burden, prevent health deterioration, and improve patients’ quality of life.

The cMORE study provides valuable insights into the prevalence and co-prevalence of type 2 diabetes-related vascular complications and comorbidities among adult patients with type 2 diabetes in the primary healthcare setting of mainland Portugal. The study demonstrates a tailored approach to treatment, with the incorporation of insulin in patients with vascular complications and highlights important considerations regarding type 2 diabetes pharmacological treatment. Despite the high rates of multimorbidity observed, vascular complications were present at a reasonable level. This, coupled with the satisfactory HbA1c levels achieved by most patients, indicates there is good management of type 2 diabetes in this population. Altogether, these findings underscore the importance of individualized management plans that take into account the unique clinical characteristics and associated comorbidities of patients with type 2 diabetes, starting from the time of diagnosis. Larger-scale studies with extended follow-up periods could provide further understanding of the long-term outcomes of these management strategies and their impact on patient health. By optimizing glycemic control and addressing concurrent conditions, healthcare providers can strive to enhance patient outcomes and mitigate the overall burden of type 2 diabetes.

Funding for this research was provided by MSD Portugal (Protocol NIS008358).

All authors are responsible for the work described in this paper. S. Alão: Study conception; T. Silva, A.P. Leite, M. Rosário, C. Carvalho, J. Coelho, H. Ferreira, R. Ferreira, J. Abreu, M. Rosa, S. Azevedo, C. Cunha, C. Daniel, B. Juane and R.A. Sousa: Data collection and analysis. All authors participated in the interpretation of data, revised the manuscript for important intellectual content and provided final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

SA and ACC are employees of MSD Portugal, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA.