Comparative effectiveness and cost-effectiveness of cardioprotective glucose-lowering therapies for type 2 diabetes in Brazil: a Bayesian network model.

BACKGROUND: The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. METHODS: We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. RESULTS: In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69-0.96)], GLP-1A [HR: 0.79 (95% CI 0.67-0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59-0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521-10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227-18,121) and Int$29,119 (95% CI: 23,811-35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. CONCLUSIONS: In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. TRIAL REGISTRATION: CRD42020194415.

Socioeconomic Factors Associated With Glycemic Measurement and Poor HbA1c Control in People With Type 2 Diabetes: The Global DISCOVER Study.

DISCOVER is a 3-year observational study program of 15,983 people with type 2 diabetes initiating second-line glucose-lowering therapy in 38 countries. We investigated the association between socioeconomic status and both the availability of a baseline glycated hemoglobin (HbA1c) measurement and poor glycemic control (HbA1c level ≥ 9.0%) in participants enrolled in DISCOVER. Factors associated with a lack of baseline HbA1c measurement or an HbA1c level ≥ 9.0% were assessed using three-level hierarchical logistic models. Overall, 19.1% of participants did not have a baseline HbA1c measurement recorded. Lower-middle country income (vs. high) and primary/no formal education (vs. university education) were independently associated with a reduced likelihood of having a baseline HbA1c measurement (odds ratio [95% confidence interval]: 0.11 [0.03-0.49] and 0.81 [0.66-0.98], respectively. Of the participants with an available HbA1c measurement, 26.9% had an HbA1c level ≥ 9.0%; 68.7% of these individuals were from lower- or upper-middle-income countries. Factors associated with an increased likelihood of poor glycemic control included low country income, treatment at a site with public and/or governmental funding (vs. private funding) and having public or no health insurance (vs. private). A substantial proportion of DISCOVER participants did not have an HbA1c measurement; more than one-quarter of these participants had poorly controlled type 2 diabetes. Both individual- and country-level socioeconomic factors are associated with the quality of care regarding glycemic control. Awareness of these factors could help improve the management of patients with type 2 diabetes.

Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020)

ABSTRACT Objective: A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Subjects and methods: We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results: A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion: Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.

Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020).

Objective: A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Methods: We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results: A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion: Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.

GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients.

BACKGROUND: Diabetes is a chronic disease with high complexity that demands strategic medical care with a multifactorial risk-reduction approach. Over the past decade, the treatment of type 2 diabetes mellitus (T2DM) has entirely changed. One of the paradigm changes has been the arrival of new drugs that reduce cardiovascular risk beyond the reduction of A1C. OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are two groups of antidiabetics drugs, which have demonstrated superiority compared to placebo for major cardiovascular events (MACE). METHODS: We update and discuss their impact on MACE expressed as relative risk (HR hazard ratio) and as the number needed to treat (NNT) to avoid one cardiovascular event in 5 years. We include the publications of the last 10 years. RESULTS: Empagliflozin, Canagliflozin and Dapagliflozin present an HR for MACE of 0.86, 0.86, 0.86 and an NNT of 38, 44, and 33, respectively (Dapagliflozin in secondary prevention). Regarding HHF (Hospitalization for Heart Failure), the HR was 0.65, 0.67, 0.73 and NNT was 44, 62, and 98, respectively. Lixisenatide, Exenatide, Liragutide, Semaglutide, Albiglutide and Dulaglutide presented for MACE an HR of 1.02, 0.91, 0.87, 0.74, 0.78, 0.88, respectively. There was no increase in the risk of HHF, but there was no benefit either. CONCLUSION: Cardiovascular benefits of the GLP-1RA and the SGLT2i are clinically significant. A number needed to treat under 50 is required to avoid one MACE in five years. These benefits have led to important changes in the Clinical Practice Guidelines and in the care of our patients with T2DM.

Recent advances in understanding/managing type 2 diabetes mellitus.

The treatment of type 2 diabetes mellitus has evolved in the present century toward safer and maybe more effective drugs, which in some cases can also reduce the risk of cardiovascular and renal outcomes. Nevertheless, we still need better strategies to reduce excess body weight in order to achieve diabetes remission, which is now a feasible target, as has been demonstrated with bariatric surgery. This review focuses on the significant advances in the management of blood glucose in type 2 diabetes mellitus, including the current understanding of the mechanisms of drug action but keeping in mind that the treatment of the disease is multifactorial.