The prevalence of diabetes is increasing at an unstoppable rate (Internacional Diabetes Federation, 2023). Type 2 diabetes (T2D) accounts for the vast majority (over 90%) of diabetes worldwide. Upon diagnosis of T2D, it is common practice to recommend hypoglycemic treatment in conjunction with lifestyle modification (Alemán et al., 2018). The timeliness of this treatment should be assessed by the physician based on the patient’s comorbidities and analytical results (mainly fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and glomerular filtration rate (GFR)) in order to select the most appropriate treatment for each patient.

The increasing availability of antidiabetic drugs (AD) for the management of T2D currently allows different options for achieving glycemic targets and choosing the therapy that best suits the individual characteristics of each patient (Dahlén et al., 2022; DeMarsilis et al., 2022). AD can be classified as “modern” or “classical” based on their mechanism of action. “Classical” correspond to those whose mechanism is based on β-cell dysfunction and insulin resistance (metformin, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, repaglinide, insulins) and “modern” those with an incretin effect and with a hypoglycaemic action at renal level (Dipeptidyl peptidase four inhibitors (DPP4i), Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 agonists (GLP1a)). After the commercialization of new drugs, especially SGLT2i and GLP1a, research analyzing their effectiveness and safety has demonstrated the increased benefits obtained versus the classical therapy, especially in individuals with certain comorbidities such as cardiovascular (CV) disease, chronic kidney disease or heart failure (Herrington et al., 2023; van der Aart-van der Beek et al., 2022; Palmer et al., 2021; Ussher and Drucker, 2023). These drugs have been shown to reduce CV mortality, slow the progression of renal impairment, and reduce the frequency of hospital readmissions for heart failure (McDonagh et al., 2022). Because of this, they have been gaining prominence as first-line drugs in certain pathologies and clinical conditions, which has been reflected in the evolution of treatment algorithms (Alemán et al., 2014; Mata et al., 2020; García Soidán, 2023).

It is necessary to analyze whether, following the introduction of these new drugs with new indications, they have become a reference in routine clinical practice. Furthermore, it is important to identify the factors associated with their prescription. In addition to the clinical characteristics of the patients and their analytical values, factors such as their socioeconomic level or geographical location must also be considered, in order to explore the existence of variations in clinical practice.

The objective of this study is to describe the pattern of AD prescription in newly diagnosed patients with T2D and to analyze the factors associated with the prescription of a modern AD.

The study population was comprised of 22,892 patients with a new T2D diagnosis, 43.52% female, mean age of 64.54 ± 13.41 years (standard deviation) (Table1). The vast majority of the population (84.68%) were native. The 54.25% of the population lived in non-depopulated areas. In terms of socioeconomic level, more than a half of the population had income of less than €18,000 per year, with differences between men and women.

With regard to the presence of comorbidities, 73.89% of patients also presented hyperlipidemia, followed by 55.08% with hypertension. Women had a higher prevalence of heart failure, depression, chronic renal failure, dementia, hypertension and obesity than men. Male exhibited a higher prevalence of chronic obstructive pulmonary disease, ischemic heart disease, hyperlipidemia, and a history of previous MACE.

In consideration of the analytical values obtained prior to the initiation of the prescription, the majority of patients had elevated FPG (mean 154 ± 57.2) and HbA1c (mean 7.4%), in addition to a decreased GFR (mean 80.5 ± 18.5).

Initial treatment with monotherapy was observed in approximately 90% of cases. Metformin was the most commonly dispensed monotherapy drug, accounting for 56.88% of prescriptions, followed by combinations with metformin (12.58%); and SGLT2i (10.68%). Over one-third of patients (36.03%) started treatment with a modern AD, including DPP4i (5.92%), GLP1a (2.21%), or SGLT2i; without differences between women and men.

In Table 2, the differences between patients with a modern AD prescription and a classical one can be observed. The non-native patients and low-income people were less prescribed of modern AD. Patients with heart failure, chronic obstructive pulmonary disease, ischemic heart disease, chronic renal failure and dementia were prescribed more modern AD. Of all patients followed, 746 had had a MACE prior to the diagnosis of T2D (3.26%), of whom 415 were subsequently prescribed a modern AD. When analyzing laboratory data, in patients with poorer FPG, HbA1c and GFR control, modern drugs were prescribed more frequently. Of the prescriptions initiated in PC, the majority were for classical AD, whereas in specialized care, the majority of prescriptions were for a modern one (p = 0.00).

Different multilevel models were tested for the total population and stratified by sex in order to know which factors were associated with the prescription of a modern AD. The model with a higher explanatory capacity was the one that combined the deprivation index, depopulation level and family medicine pressure as the BHA variables. The results of this model can be found in Table 3. In the adjusted models, we observed that the odds of prescription of modern AD decreased with age, with the group aged from 65–79 years old being the lowest one of using modern AD (odds ratio (OR) 0.48; 95% confidence interval (95%CI) 0.41–0.58). No differences were observed by sex. There were differences by socioeconomic level. So, pensioners presented the lowest probability of modern AD, being statistically significant only in women. In both sexes, patients with heart failure, ischemic heart disease, chronic renal failure, obesity and a previous MACE had more probability of having a prescription of modern AD, in addition to patients with higher FPG, HbA1c and lower GFR.

The final section of Table 3 presents the parameters associated with the model. σ2 represents the overall variance of the model, τ00 corresponds to the variances of the random effects, which are the grouping levels, ICC is the intra-class correlation index, indicating how similar the observations are within each class. In other words, it indicates that part of the total variability is due to the variability of the observations in the levels.

The influence of BHA variables can be observed in Figure 2. According to the depopulation level, non-depopulated areas presented the lowest risk of modern AD prescription. So, less deprived areas showed a higher probability of modern AD prescription, that decreases with the increase of deprivation until quartile 3, as is the case with family medicine pressure that increased the risk of modern AD prescription with the increasing pressure until quartile 3. There were not differences by sex as shown in Supplementary Appendix S2.

In this population-based study conducted in patients with T2D newly diagnosed we observed differences at the individual level and by area of residence in the risk of receiving a modern AD prescription. People who were younger, had more comorbidities, higher socioeconomic level and lived in less deprived areas and depopulated areas were more likely to have a modern AD prescription.

Our study population of patients newly diagnosed with T2D were mostly male (table 1), with a mean age of 64.54, native-born and living in non-depopulated areas and with low incomes. The mean age at which diabetes was diagnosed in the subjects of our study was 64.54 years (SD = 13.41). This finding is consistent with those reported in other studies conducted in Aragón (Moreno-Juste et al., 2020) but higher than that reported in other studies both national (Mata-Cases et al., 2016; Rojo-Martínez et al., 2020) and international (Wang et al., 2019).

Our analyses revealed no significant discrepancies in the proportion of modern AD prescribed between male and female subjects. Nevertheless, the available evidence is inconclusive and exhibits inconsistencies across the studies examined (Ali et al., 2022; Choe et al., 2018) analyzing sex differences in prescribing pattern of AD. Moreover, as in our study, it has been previously described a lower prescription of SGLT2i and GLP1a in older, lower-income and immigrant populations (Ali et al., 2022; Lamprea-Montealegre et al., 2022; Montvida et al., 2018). It may be that factors such as difficulties in communication, adherence to treatment or the higher cost of modern drugs contribute to a lower frequency of prescription in these population groups (Ali et al., 2022; Lamprea-Montealegre et al., 2022; Montvida et al., 2018). Nevertheless, it is important to note that in Spain, all AD are classified as reduced-contribution treatments, whereby the patient is required to pay a fixed contribution of 10% of the retail price of the package. Furthermore, the maximum payable amount per package is set at 4.24€.

In our study, patients with comorbidities such as heart failure, ischemic heart disease, chronic renal failure, obesity and a previous MACE had a higher probability of having a prescription of modern AD. Novel AD SGLT2i and GLP1a, have shown impressive CV benefits, particularly in reducing heart failure hospitalization, CV death, and demonstrated beneficial effects on cardiac function (Nikolaidou et al., 2024). In adults with T2D, SGLT2i and GLP1a (but not DPP4i) reduce all-cause mortality and MACE compared with usual care. SGLT2i reduce chronic renal failure progression and heart failure hospitalization and GLP1a reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2i and GLP1a than with insulin or sulfonylureas (Qaseem et al., 2024).

In light of these considerations, clinical guidelines have been revised to designate these drugs as the first treatment option for this patient population (Davies et al., 2022). Until 2022, metformin was the primary treatment option, with treatment selection based on HbA1c levels (Bae et al., 2022). At present, comorbidities are given precedence, followed by consideration of the HbA1c level.

The majority of our patients started treatment in monotherapy and were most frequently prescribed metformin as similarly as described in a study in Catalonia (Ouchi et al., 2023). In this study also patients starting in combination therapy had higher HbA1c levels than those starting monotherapy. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach (Kim and Kim, 2024).

With the development of new classes of AD, the paradigm of therapeutic options for patients with glycemic and CV risk factors has shifted significantly. However, the way in which this has occurred in actual practice, especially in terms of the balance between older and newer ADs as initial and intensification therapeutic options, has undergone a much slower change (Montvida et al., 2018; Carney et al., 2022). According to a UK study (Young et al., 2023), the recent UK T2D treatment guideline represents a quasi-population indication for treatment with SGLT2i. In addition to these findings, an evaluation in the Netherlands showed that the prescription rate of SGLT2i was lower than would be indicated based on the CV risk of the patients in the absence of contraindications to their use (Hart et al., 2023). Both studies showed that these treatments were prescribed less than needed, despite being indicated for many more patients.

According to our results, the most deprived areas and non-depopulated areas presented less probability of prescription of a modern AD. Previous studies have shown that higher deprivation level is associated with higher prevalence and incidence of T2D (36,37), chronic diabetes complications, indicators of cardiometabolic risk (Laraia et al., 2012), mortality, and hospitalization due to diabetes complications (Choi et al., 2020). It is also related to worse disease control (Durfey et al., 2019) and higher treatment use (Frazer and Frazer, 2020; Di Filippo et al., 2022). It is suggested that more expensive drugs were favoured in areas with lower deprivation even for similar indications. Possible explanations include an unconscious prescriber bias towards newer and more expensive medications in affluent areas, or a more educated population likely to request newer medications (Frazer and Frazer, 2020). This phenomenon has been described for numerous chronic conditions (Di Filippo et al., 2022) and it can widen the gap in disease management and outcomes.

Regarding the multilevel model, it explained 8.5% of the variability, of which 7.3% corresponded to individual variables and 1.2% to BHA variables. It was similar when differentiating between women and men. This means that belonging to an area had very little effect on the prescription of a modern AD and that the variability was explained more by individual patient factors.

Sociodemographic, clinical and regional factors are associated with variability in the prescribing pattern. Our findings are helpful for understanding the use of these drugs and the predictors of their prescription, in order to better assess and understand the health outcomes of people with T2D.

The implementation of current clinical guidelines needs to be adapted to explicitly consider socio-economic and territorial factors. Although guidelines do not usually incorporate aspects such as deprivation, depopulation or care pressure, these determinants should be considered when applying them to ensure more equitable clinical practice. To this end, specific strategies such as prescription audits, targeted professional training and clinical decision support systems should be incorporated in areas with higher levels of inequality or family medicine pressure.