In total, 622 records were identified in the literature search. After removing 175 duplicate records, the remaining 448 articles were subjected to title and abstract screening. Of these, 71 articles underwent full-text screening, and 28 relevant publications reporting 27 studies met the inclusion criteria and were included in the SLR (Fig. 1).

PRISMA diagram of the study selection process

Of these studies, 16 studies were conducted in the US, six studies were conducted in Germany, and three studies were conducted in Canada. Additionally, three multicountry studies (two studies in the US and Canada and one international study that included Canada and Germany) were included. Most studies concerning T2DM (55%) and HF (63%) were conducted in the US (Fig. 2).

Geographical location of the included studies by disease area

In total, 11 studies focused on T2DM guidelines, and 16 studies focused on HF guidelines. The following value areas were identified in the guidelines considered: pharmacological intervention, defined as guideline recommendations involving drug(s) to treat T2DM or HF; monitoring defined as guideline recommendations involving the monitoring of clinical, biochemical, or radiological parameters for managing T2DM or HF; monitoring and pharmacological intervention defined as guideline recommendations for pharmacological intervention and monitoring; and diagnosis, monitoring, and pharmacological intervention defined as guideline recommendations involving early diagnosis/screening, pharmacological intervention, and monitoring. Among the identified studies, 11 studies considered guidelines concerning pharmacological intervention, five studies considered guidelines concerning monitoring, nine studies considered guidelines concerning monitoring and pharmacological intervention, and two studies considered guidelines concerning diagnosis, monitoring, and pharmacological intervention (Supplementary Figure S1).

Regarding the settings and study designs, eight studies involved patients treated in both outpatient and hospital settings, while 11 studies involved patients from multiple settings. Eighteen studies adopted a retrospective study design, seven studies adopted a prospective design, and two studies were RCTs. Most studies focused on clinical outcomes, while few studies focused on QoL (two studies) and economic (one study) outcomes.

Of the studies focusing on T2DM guidelines, seven studies considered only T2DM, while three studies considered T2DM along with the following comorbidities: CKD; hypertension; and coronary heart disease, ischemic stroke, myocardial infarction (MI), and HF. Therefore, some studies included evidence concerning adherence to more than one guideline. Nelson et al. [25] discussed guideline-directed treatment but did not specify the guideline. The guidelines considered in each T2DM study are shown in Table 1.

Of the studies focusing on HF guidelines, 16 studies investigated adherence to HF guidelines. Fourteen studies reported the specific guideline(s) considered, while four studies did not specify the guideline [26,27,28,29,30]. Some studies included evidence concerning adherence to more than one guideline. The guidelines considered in each HF study are shown in Table 2.

Among all studies, only 16 studies had a sample size > 1000 patients. Among the T2DM studies, the study with the smallest sample size was a randomized controlled feasibility study involving 50 patients [31], while the study with the largest sample size involved an analysis of an administrative claims database containing data from 1,881,447 patients [32]. The median age of the participants ranged from 49.6 years [31] to 78.3 years [33], albeit Hartzler et al. [34] reported an age range of 20–69 years. Regarding the sex distribution, the percentage of male patients included in the studies ranged from 16% [31] to 63% [35]. Data pertaining to race were only reported in one study in which the majority of the participants (58%) were White [32].

Among the HF studies, the study with the smallest sample size involved a retrospective cohort analysis of data from 250 patients [36], while the study with the largest sample size involved an analysis of claims and electronic health record data from 144,074 patients [29]. The median age of the participants ranged from 56 years [37] to 79.5 years [30]. Regarding the sex distribution, the percentage of male patients included in the studies ranged from 39% [38] to 99% [28], with one study not reporting the sex distribution in the population [26]. Data pertaining to race were only reported in eight studies, and the proportion of White participants ranged from 50% [37] to 90% [36].

The proportion of patients with T2DM receiving treatment fully adherent to clinical guidelines was considerably varied across the studies from 11.2% (in managing HF in patients with T2DM) to 42.6% (in managing ischemic stroke in patients with T2DM). Adherence to individual recommendations varied considerably: the adherence rate for pharmacological interventions (i.e., high-intensity statins, angiotensin-converting enzyme inhibitors [ACEIs]/angiotensin II receptor blockers [ARBs], and sodium/glucose cotransporter-2 inhibitors [SGLT-2is]/glucagon-like peptide 1 receptor agonists [GLP-1RAs]) ranged from 2.7% of patients prescribed three evidence-based therapies to 83% of specialist doctors prescribing treatment as per the German national treatment guidelines for type 2 diabetes. The adherence rate for monitoring recommendations ranged from 0% of patients receiving comprehensive foot examinations in a subgroup of patients to 100% of patients being monitored for blood pressure (BP). The adherence rate for CKD screening was 49.1%, while the overall adherence rate for screening recommendations in patients with T2DM (i.e., hemoglobin A1c [HbA1c], BP, low-density lipoprotein [LDL], estimated glomerular filtration rate [eGFR], and creatinine levels) was 55%. Among patients with HF alone, guideline adherence was higher, ranging from 14.5 to 93.4% (average 40.4%). Most studies on heart failure guidelines focused on adherence to pharmacological interventions (i.e., aldosterone antagonists [AA], ACEIs, ARBs, angiotensin receptor neprilysin inhibitors [ARNIs], beta-blockers [BB], and mineralocorticoid receptor antagonists [MRAs]). Supplementary Tables S7 and S8 present a summary of the definitions of guideline adherence applied in the included studies. This information was extracted, as reported by the authors in the included studies. Briefly, most studies defined guideline adherence in terms of pharmacological intervention, such as the proportion of patients receiving recommended medication (e.g., number of therapies, medication classes, dosage), followed by monitoring (i.e., laboratory tests) and proportion of patients following recommendations.

A summary of the studies focusing on T2DM guidelines is provided in Supplementary Table S9. The main outcomes of interest in these studies included all-cause mortality; all-cause hospitalization; development of complications; long-term changes in HbA1c, BP, and LDL; new onset of and progression to HF and CKD; and QoL. In Germany, among patients with T2DM at risk of developing CVD, a lack of guideline adherence was associated with a higher risk of death compared with the risk in patients receiving fully adherent treatment [39]. In the US, physician adherence to screening recommendations and the use of medication recommended in the guidelines by the ADA were protective against all-cause mortality [33]. In Germany, the risk of all-cause hospitalization among patients receiving treatment that is nonadherent or partly adherent to guideline-directed treatment was significantly higher than that of patients receiving fully adherent treatment, and a lack of guideline adherence (nonadherence or partial adherence) was associated with a higher risk of hospitalization due to comorbid HF, stroke, or MI in patients with T2DM [39]. In the US, screening adherence to ADA guidance was protective against a first diagnosis of chronic HF, acute MI, and stroke/transient ischemic attack following the initial diabetes diagnosis. Additionally, adherence to the recommended medication was protective against acute MI and stroke/transient ischemic attack [33]. In Canada, increasing the use of evidence-based therapies was reported to reduce major atherosclerotic cardiovascular events, including MI, stroke, and cardiovascular death in eligible but untreated patients. The estimated attributable risk reduction was 1.33% per therapy considered, including high-intensity statin, either an ACEI or ARB, and either a SGLT-2is or a GLP-1RAs, with a total decrease of 4443 major adverse cardiovascular events within 3 years [25].

In the US, compared with those who did not receive adherent treatment, adherence to ADA guidelines significantly improved the HbA1c levels at 6 months; additionally, adherence to ADA guidelines improved systolic BP and reduced LDL levels, but these differences were not significant [31]. In Germany, adherence to the ESC and the EASD guidelines enabled patients to achieve their BP and LDL goals, and their target attainment was higher than that observed in the nonadherent group [35].

In the US, adherence to ADA guidelines led to the monitoring of kidney damage and function in patients with T2DM, enabling a timely diagnosis of CKD, preventing the onset of disease progression and enabling informed decisions regarding treatment initiation and/or intensification. Screening adherence to the ADA guidelines and adherence to recommended medications were protective against a first diagnosis of congestive HF [33].

A summary of the studies focusing on HF guidelines is provided in Supplementary Table S10. The main outcomes of interest in the studies focusing on T2DM guidelines included all-cause mortality, all-cause hospitalization, development of complications, and economic outcomes. In the US, patients who underwent ischemic evaluations according to monitoring guidelines exhibited a significantly lower adjusted hazard of all-cause mortality than those who did not undergo an evaluation [28]. Adherence to pharmacological intervention guidelines was associated with lower 30-day and 1-year mortality rates [27]. The use of the guideline-directed pharmacological intervention ACEIs was significantly correlated with the 30-day and 1-year mortality rates [43]. The use of an AA according to guidelines was associated with a lower 30-day mortality rate [44]. The use of BBs and ARNIs according to the 2013 guidelines by the American College of Cardiology Foundation/American Heart Association, was inversely correlated with facility-level mortality [29]. Adherence to guideline-directed treatment led to lower mortality rates among patients newly diagnosed with HF with reduced ejection fraction (HFrEF) and those with a history of incident HF-related hospitalization [45]. In Canada, adherence to guideline-directed treatment in patients with HFrEF reduced all-cause mortality for 0–365 days after hospital discharge [46].

Regarding all-cause hospitalization, in the US, adherence to guideline-directed treatment led to low 30-day readmission rates [30]. Additionally, a modest association was observed between the guideline-direct pharmacological use of an AA and 30-day readmission rates [44]. Adherence to guideline-directed treatment further led to lower rehospitalization rates in patients newly diagnosed with HFrEF and those with a history of incident HF-related hospitalizations [45]. In terms of complications, in the US, monitoring adherent to the guidelines by the American College of Cardiology/American Heart Association led to improved eGFR levels [38].

One study conducted in Canada considered the economic outcomes of guideline adherence and showed that physician-led multidisciplinary heart function clinics exhibited higher adherence to guideline-directed treatment and significantly lower rates of rehospitalization, resulting in cost-effective HF management with usual care [26]. No studies reported the economic outcomes of adherence to treatment guidelines for T2DM and its comorbidities.

Finally, only two studies examined the impact of guideline adherence on patients’ QoL, providing limited evidence. In Germany, patients’ Problem Areas in Diabetes (PAID-2) scores improved in parallel with improved adherence to guidelines [40]. PAID-2 is commonly used to assess diabetes-related distress and patients’ adjustment to diabetes [41]. In the US, adherence to ADA guidelines with a stricter HbA1c target was associated with an improved QoL as measured by EQ-5D [34], a questionnaire commonly used to assess health-related QoL [42].

In summary, adherence to guidelines for managing T2DM and its comorbidities and adherence to guidelines for managing HF both led to a decrease in all-cause mortality and all-cause hospitalizations as well as fewer hospitalizations due to HF. Furthermore, guideline adherence was shown to help patients achieve better long-term control of their BP and LDL and reduce long-term complications. Overall, the studies focusing on HF guidelines mainly considered mortality and hospitalizations, and, thus, evidence gaps were noted in terms of the impact of guideline adherence for both T2DM and HF on economic and QoL outcomes.