Chronic heart failure (CHF) is a growing global health burden, affecting over 64 million individuals worldwide and conferring significant morbidity and mortality. Type 2 diabetes mellitus (T2DM) is a highly prevalent comorbidity, coexisting in approximately 30–40% of heart failure patients and independently worsening prognosis through accelerated myocardial dysfunction, endothelial injury, and heightened neurohormonal activation.

Beta-adrenergic receptor blockers constitute a Class I recommendation in the management of CHF with reduced ejection fraction (HFrEF), having demonstrated substantial reductions in mortality, hospitalizations, and reverse remodeling in landmark trials including MERIT-HF, COPERNICUS, and CIBIS-II.^5,11 However, the concurrent presence of T2DM introduces a therapeutic dilemma: traditional beta-blockers, particularly non-vasodilating agents such as metoprolol and atenolol, are associated with worsening glycemic control, increased insulin resistance, dyslipidemia, weight gain, and masking of hypoglycemic symptoms.^8,9

Metoprolol succinate, a widely prescribed selective beta-1 blocker, has strong evidence supporting its use in HFrEF from the MERIT-HF trial.¹¹ Despite its proven cardiac benefits, concerns regarding its adverse metabolic effects persist, particularly in diabetic patients who are already at elevated cardiometabolic risk.^15,16

Nebivolol is a third-generation, highly selective beta-1 adrenergic blocker distinguished by its unique capacity to stimulate endothelial nitric oxide (NO) synthase via activation of the beta-3 adrenergic receptor and the L-arginine/NO pathway.^6,7 This vasodilatory mechanism confers several putative advantages: improved peripheral insulin sensitivity, favorable effects on lipid metabolism, reduced peripheral vascular resistance, and enhanced endothelial function.^8,12 The SENIORS trial established the efficacy of nebivolol in elderly heart failure patients, demonstrating a significant reduction in the composite endpoint of all-cause mortality and cardiovascular hospitalization.¹⁰

Despite these pharmacological advantages, head-to-head clinical data directly comparing nebivolol and metoprolol in CHF patients with coexisting T2DM remain sparse, particularly from the Indian subcontinent where the dual burden of heart failure and diabetes is disproportionately high. The present study was therefore designed to compare the effects of nebivolol versus metoprolol succinate on cardiac function, glycemic control, insulin resistance, and lipid parameters in patients with CHF and T2DM in a prospective, randomized clinical trial setting.

Study Design and Setting This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Department of General Medicine, Shri Atal Bihari Vajpayee Medical College and Research Institute, Bangalore, India, over a 12-month period from April 2025 to March 2026. Study Population Inclusion Criteria: Patients aged 18–75 years with an established diagnosis of CHF (NYHA functional class II or III) and LVEF ≤40% on transthoracic echocardiography, with coexisting T2DM (diagnosed per ADA criteria or on stable antidiabetic therapy for ≥3 months), and on stable guideline-directed medical therapy (GDMT) for heart failure for at least 4 weeks prior to randomization were eligible for inclusion. Exclusion Criteria: Patients with NYHA class IV heart failure, acute decompensated heart failure within 4 weeks, type 1 diabetes mellitus, HbA1c >10%, resting heart rate <60 bpm, systolic blood pressure <90 mmHg, second- or third-degree atrioventricular block, severe hepatic impairment (Child-Pugh class C), estimated GFR <30 mL/min/1.73m², severe obstructive airway disease, known hypersensitivity to study medications, pregnancy or lactation, and those currently on beta-blocker therapy were excluded. Randomization and Intervention Eligible patients were randomized in a 1:1 ratio using computer-generated random number sequences with block randomization (block size of 4) to one of two treatment arms. Allocation concealment was maintained using sequentially numbered opaque sealed envelopes. The Nebivolol Group (n=60) received nebivolol initiated at 1.25 mg once daily, up-titrated every 2 weeks to a target dose of 5–10 mg/day as tolerated. The Metoprolol Group (n=60) received metoprolol succinate (extended-release) initiated at 12.5–25 mg once daily, up-titrated every 2 weeks to a target dose of 50–200 mg/day per standard guidelines. All other CHF medications (ACE inhibitors/ARBs, diuretics, mineralocorticoid receptor antagonists, and antidiabetic agents) were continued as per baseline therapy and were not altered during the study period unless clinically mandated. Outcome Measures Primary Outcomes: Change in LVEF (%) assessed by transthoracic echocardiography (modified Simpson's biplane method) and change in NYHA functional class from baseline to 12 months. Secondary Outcomes: Changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides), NT-proBNP levels, resting heart rate, systolic and diastolic blood pressure, 6-minute walk distance (6MWD), and adverse event profile. Data Collection and Follow-up All assessments were performed at baseline, 3 months, 6 months, 9 months, and 12 months. Echocardiographic examinations were conducted by a single experienced cardiologist blinded to treatment allocation using a Philips EPIQ CVx system. Biochemical parameters were analyzed at the institutional central laboratory using standardized automated assays. HbA1c was measured by high-performance liquid chromatography (HPLC, Bio-Rad D-10), fasting insulin by chemiluminescence immunoassay (CLIA, Beckman Coulter Access 2), and NT-proBNP by electrochemiluminescence immunoassay (ECLIA, Roche Cobas e411). HOMA-IR was calculated as: [fasting insulin (µU/mL) × fasting glucose (mg/dL)] / 405. Sample Size Calculation Based on published data from prior beta-blocker trials in heart failure, a mean difference in LVEF change of 2.0% between groups with a pooled standard deviation of 4.0% was anticipated. Using a two-sided alpha of 0.05 and 80% power, a minimum of 50 patients per group was required. Accounting for an anticipated dropout rate of 15%, 60 patients were enrolled in each arm (total N=120). Statistical Analysis Data were analyzed on an intention-to-treat (ITT) basis. Continuous variables were expressed as mean ± standard deviation (SD) and compared using the independent samples t-test or Mann-Whitney U test as appropriate. Categorical variables were expressed as frequencies and percentages and compared using the chi-square test or Fisher's exact test. Within-group changes were assessed using paired t-tests. Repeated-measures ANOVA with Bonferroni correction was used for longitudinal comparisons. A two-tailed p-value of <0.05 was considered statistically significant. All analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism 9.0.

Patient Disposition and Baseline Characteristics

A total of 186 patients were screened, of whom 120 met the eligibility criteria and were randomized (60 per group). During the 12-month follow-up, 6 patients in the nebivolol group (4 lost to follow-up, 2 discontinued due to adverse events) and 8 in the metoprolol group (5 lost to follow-up, 3 discontinued) did not complete the study. ITT analysis included all 120 randomized patients (Figure 1). Baseline demographic and clinical characteristics were comparable between the two groups with no statistically significant differences (Table 1).

Figure 1. CONSORT flow diagram showing patient enrollment, allocation, follow-up, and analysis.

Table 1. Baseline Demographic and Clinical Characteristics of the Study Population

Values are mean ± SD or n (%). CHF: chronic heart failure; T2DM: type 2 diabetes mellitus; BMI: body mass index; NYHA: New York Heart Association; LVEF: left ventricular ejection fraction; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG: fasting blood glucose; HOMA-IR: homeostatic model assessment of insulin resistance; 6MWD: 6-minute walk distance; ACEi: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; MRA: mineralocorticoid receptor antagonist.

Primary Outcomes

Left Ventricular Ejection Fraction

Both treatment groups demonstrated significant improvement in LVEF over the 12-month study period. The nebivolol group showed an increase from 32.8 ± 4.5% at baseline to 39.2 ± 5.2% at 12 months (mean change: +6.4 ± 3.8%; p<0.001), while the metoprolol group improved from 33.1 ± 4.3% to 37.6 ± 4.8% (mean change: +4.5 ± 3.5%; p<0.001). The between-group difference in LVEF change was statistically significant, favoring nebivolol (p=0.041) (Table 2, Figure 2).

Figure 2. Changes in left ventricular ejection fraction (LVEF) at baseline, 6 months, and 12 months. Error bars represent standard error of the mean. *p = 0.041 for between-group comparison at 12 months.

NYHA Functional Class

Improvement of at least one NYHA functional class was observed in 38 patients (63.3%) in the nebivolol group compared with 32 patients (53.3%) in the metoprolol group (p=0.268). Among patients initially classified as NYHA class III, improvement to class II was recorded in 18 of 24 (75.0%) nebivolol-treated patients versus 16 of 25 (64.0%) metoprolol-treated patients (p=0.398). The mean NYHA class decreased from 2.40 ± 0.49 to 1.78 ± 0.56 in the nebivolol group and from 2.42 ± 0.50 to 1.88 ± 0.59 in the metoprolol group, with no significant between-group difference (p=0.342).

6-Minute Walk Distance

The 6MWD increased significantly in both groups: nebivolol from 312 ± 58 m to 388 ± 52 m (Δ+76 m; p<0.001) and metoprolol from 305 ± 62 m to 368 ± 58 m (Δ+63 m; p<0.001). The between-group difference approached but did not reach statistical significance (p=0.072).

Table 2. Primary Cardiac Outcomes at 12 Months

*p-value for between-group comparison of change from baseline (Δ). Values are mean ± SD. Bold p-values indicate statistical significance (p<0.05).

Secondary Outcomes: Metabolic Parameters

Glycemic Control

Significant divergence in glycemic trajectories was observed between the two groups over 12 months (Figure 3). HbA1c decreased from 7.62 ± 0.82% to 7.34 ± 0.68% in the nebivolol group (mean change: −0.28 ± 0.58%; p=0.008), whereas it increased from 7.58 ± 0.78% to 7.91 ± 0.85% in the metoprolol group (mean change: +0.33 ± 0.62%; p=0.004). The between-group difference in HbA1c change was highly significant (p<0.001). A similar pattern was observed for FBG: nebivolol was associated with a reduction from 148.5 ± 22.4 to 138.2 ± 18.6 mg/dL (Δ−10.3 mg/dL; p=0.006), while metoprolol led to an increase from 150.1 ± 24.8 to 158.7 ± 26.4 mg/dL (Δ+8.6 mg/dL; p=0.038), with a significant between-group difference (p<0.001).

Figure 3. Trajectory of HbA1c (%) over the 12-month follow-up period. Error bars represent standard error of the mean. *p < 0.001 for between-group comparison at 12 months.

Insulin Resistance

HOMA-IR demonstrated a favorable decline in the nebivolol group from 3.85 ± 1.12 to 3.42 ± 0.98 (Δ−0.43 ± 0.85; p=0.012), in contrast to a significant increase in the metoprolol group from 3.78 ± 1.18 to 4.25 ± 1.35 (Δ+0.47 ± 1.02; p=0.018). The between-group difference was statistically significant (p<0.001). Fasting insulin levels remained stable in the nebivolol group (11.8 ± 3.2 to 11.2 ± 2.8 µU/mL; p=0.264) but increased in the metoprolol group (11.5 ± 3.4 to 12.8 ± 3.8 µU/mL; p=0.042).

Lipid Profile

Nebivolol showed favorable effects on triglycerides (178.3 ± 38.5 to 162.5 ± 32.4 mg/dL; Δ−15.8 mg/dL; p=0.014) and HDL-C (38.2 ± 6.8 to 41.8 ± 7.2 mg/dL; Δ+3.6 mg/dL; p=0.006), while metoprolol was associated with a non-significant increase in triglycerides (175.8 ± 36.2 to 186.4 ± 40.8 mg/dL; Δ+10.6 mg/dL; p=0.108) and no significant change in HDL-C (39.1 ± 7.2 to 38.4 ± 7.6 mg/dL; p=0.582). Between-group differences were significant for triglycerides (p=0.009) and HDL-C (p=0.022). No significant between-group differences were observed in total cholesterol (p=0.318) or LDL-C (p=0.452).

Figure 4. Changes in metabolic parameters from baseline to 12 months: (A) Fasting blood glucose, (B) HOMA-IR, and (C) Serum triglycerides. Error bars represent standard error of the mean.

Table 3. Secondary Metabolic Outcomes at 12 Months

BL: baseline; 12M: 12 months; Neb: nebivolol; Met: metoprolol; FBG: fasting blood glucose; TC: total cholesterol; TG: triglycerides. Bold p-values indicate statistical significance. †Between-group comparison of change from baseline.

NT-proBNP Levels

Both groups demonstrated a marked and comparable reduction in NT-proBNP levels over the 12-month period. In the nebivolol group, NT-proBNP declined from 1285 ± 385 pg/mL to 648 ± 218 pg/mL (Δ−637 pg/mL; 49.6% reduction; p<0.001). In the metoprolol group, NT-proBNP declined from 1312 ± 402 pg/mL to 724 ± 245 pg/mL (Δ−588 pg/mL; 44.8% reduction; p<0.001). The between-group difference was not statistically significant (p=0.138), suggesting equivalent neurohormonal benefit (Figure 5).

Figure 5. NT-proBNP levels (pg/mL) over the 12-month follow-up period. Error bars represent standard error of the mean. p = 0.138 for between-group comparison at 12 months.

Safety and Adverse Events

Table 4. Adverse Events During the 12-Month Study Period

Values are n (%). HF: heart failure. None of the individual adverse event comparisons reached statistical significance.

Both study medications were generally well tolerated. Drug-related adverse events leading to discontinuation occurred in 2 patients (3.3%) in the nebivolol group and 3 patients (5.0%) in the metoprolol group (p=0.648). A numerically higher incidence of weight gain (>2 kg) was observed in the metoprolol group (16.7% vs 6.7%; p=0.088), as was new-onset hypoglycemia (8.3% vs 1.7%; p=0.094), though neither reached statistical significance. Heart failure hospitalization occurred in 4 nebivolol-treated patients (6.7%) and 6 metoprolol-treated patients (10.0%; p=0.510). There were 3 deaths during the study (1 nebivolol, 2 metoprolol), all attributed to cardiovascular causes.

The present study provides robust evidence that nebivolol offers significant metabolic advantages over metoprolol succinate in patients with CHF and coexisting T2DM, while delivering at least comparable — and potentially superior — cardiac benefits. To our knowledge, this is among the first prospective, randomized, head-to-head comparisons of these two widely used beta-blockers specifically focused on the interplay between cardiac function and metabolic parameters in this high-risk dual-disease population from the Indian subcontinent. The key finding of our study is the markedly divergent effect of these agents on glycemic control. Nebivolol treatment was associated with a statistically significant reduction in HbA1c (−0.28%), fasting glucose (−10.3 mg/dL), and HOMA-IR (−0.43), whereas metoprolol produced deterioration across all three parameters (HbA1c +0.33%, FBG +8.6 mg/dL, HOMA-IR +0.47). These findings are consistent with the observations of Celik et al., who reported improved insulin sensitivity with nebivolol compared with metoprolol in hypertensive patients,8 and align with the metabolic findings of Erdogan et al. in non-diabetic hypertensive subjects.12 The clinical significance of these metabolic differences should not be underestimated: Aguilar et al. demonstrated that each 1% increase in HbA1c in CHF patients with diabetes was associated with a 12–14% increase in mortality risk,18 underscoring that beta-blocker selection can have implications extending beyond immediate cardiac outcomes. The superior metabolic profile of nebivolol is pharmacologically attributable to its unique mechanism of action. Unlike conventional beta-1 selective agents, nebivolol stimulates endothelial nitric oxide synthase (eNOS) through beta-3 adrenergic receptor agonism, leading to enhanced NO bioavailability.6,7 This NO-mediated vasodilation improves skeletal muscle blood flow and glucose uptake, enhances insulin signaling pathways, and reduces peripheral vascular resistance — mechanisms collectively responsible for the observed improvements in insulin sensitivity and glycemic control.14 In contrast, metoprolol, while highly beta-1 selective, lacks vasodilatory properties and may impair insulin-mediated glucose disposal through reduction in skeletal muscle perfusion and inhibition of pancreatic beta-cell insulin secretion.15,16 Regarding lipid metabolism, nebivolol demonstrated favorable effects on triglycerides (−15.8 mg/dL) and HDL-C (+3.6 mg/dL), while metoprolol showed a trend toward triglyceride elevation (+10.6 mg/dL) with no meaningful change in HDL-C. These findings parallel the observations of Bakris et al., who reported metabolic advantages of the vasodilating beta-blocker carvedilol over metoprolol in the GEMINI trial,16 and reinforce the concept that vasodilating beta-blockers as a class may offer lipid-neutral or lipid-beneficial effects. With respect to cardiac outcomes, both agents produced significant improvements in LVEF, NT-proBNP, heart rate, and 6MWD, confirming the established role of beta-blockade in reverse remodeling.5,11 Notably, nebivolol demonstrated a statistically significant greater increase in LVEF (Δ6.4% vs Δ4.5%; p=0.041) and a numerically greater improvement in 6MWD, which approached significance (p=0.072). These findings are consistent with the data from the CARNEBI trial, which demonstrated favorable hemodynamic and functional effects of nebivolol compared with bisoprolol in moderate heart failure,25 and with echocardiographic observations by Nodari et al.22 The marginally superior LVEF improvement with nebivolol may be attributable to the additive benefit of NO-mediated afterload reduction and improved myocardial energetics. NT-proBNP declined substantially and comparably in both groups (nebivolol: −49.6%; metoprolol: −44.8%; p=0.138), suggesting equivalent neurohormonal suppression. This parity in biomarker response is reassuring and aligns with the SENIORS trial subgroup analysis by De Boer et al., which demonstrated comparable nebivolol efficacy in heart failure patients with and without diabetes.29 The safety profile in our study was consistent with established beta-blocker pharmacology. Of particular clinical relevance, the metoprolol group exhibited a numerically higher incidence of new-onset hypoglycemia (8.3% vs 1.7%) and weight gain >2 kg (16.7% vs 6.7%), both of which, while not reaching statistical significance in our sample size, represent clinically meaningful trends in diabetic patients. Traditional beta-blockers are known to mask adrenergic symptoms of hypoglycemia and impair counterregulatory gluconeogenesis,9 effects that are attenuated with vasodilating agents like nebivolol. These findings, combined with the glucose-lowering effect of nebivolol, suggest a fundamentally more favorable risk-benefit ratio for nebivolol in the diabetic heart failure population. Strengths and Limitations Strengths of this study include its prospective randomized design, comprehensive metabolic phenotyping at multiple time points, echocardiographic assessment by a blinded operator, adequate follow-up duration, and focus on a clinically important yet understudied population — heart failure patients with diabetes in the Indian context. Several limitations warrant acknowledgment. The open-label design introduces the potential for performance bias, although objective endpoints (LVEF by blinded echocardiography, biochemical parameters) mitigate this concern. The sample size, while adequately powered for the primary endpoint, was insufficient to detect statistically significant differences in relatively infrequent adverse events such as hypoglycemia or mortality. The single-center design may limit generalizability. Furthermore, the 12-month follow-up period may be insufficient to capture longer-term cardiovascular outcomes and mortality differences. Larger, multicenter, double-blinded trials with extended follow-up are needed to confirm and extend these findings.

In patients with chronic heart failure and coexisting type 2 diabetes mellitus, nebivolol demonstrates a significantly superior metabolic profile compared with metoprolol succinate, manifested by improvements in HbA1c, fasting glucose, insulin resistance, triglycerides, and HDL cholesterol, while metoprolol was associated with deterioration in glycemic and insulin sensitivity parameters. Both agents produced significant and broadly comparable improvements in cardiac function and neurohormonal markers, with nebivolol showing a marginally greater increase in LVEF. These findings support the preferential use of nebivolol over metoprolol in the management of heart failure patients with concomitant diabetes mellitus, particularly in clinical settings where metabolic risk optimization is a therapeutic priority.

1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37(27):2129-2200.
2. Seferovic PM, Petrie MC, Filippatos GS, et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20(5):853-872.
3. Dunlay SM, Givertz MM, Aguilar D, et al. Type 2 Diabetes Mellitus and Heart Failure: A Scientific Statement From the American Heart Association and the Heart Failure Society of America. Circulation. 2019;140(13):e294-e324.
4. Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J. The sympathetic nervous system in heart failure: physiology, pathophysiology, and clinical implications. J Am Coll Cardiol. 2009;54(19):1747-1762.
5. Bristow MR. Beta-adrenergic receptor blockade in chronic heart failure. Circulation. 2000;101(5):558-569.
6. Fongemie J, Felix-Getzik E. A Review of Nebivolol Pharmacology and Clinical Evidence. Drugs. 2015;75(12):1349-1371.
7. Weiss R. Nebivolol: a novel beta-blocker with nitric oxide-induced vasodilatation. Vasc Health Risk Manag. 2006;2(3):303-308.
8. Celik T, Iyisoy A, Kursaklioglu H, et al. Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients. J Hypertens. 2006;24(3):591-596.
9. Marketou ME, Zacharis EA, Koukouraki S, et al. Effect of beta-blocker therapy on glucose homeostasis and insulin resistance in patients with heart failure. Am J Ther. 2012;19(6):429-435.
10. Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26(3):215-225.
11. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001-2007.
12. Erdogan O, Ertem B, Altun A. Comparison of the effects of nebivolol and metoprolol on insulin sensitivity in hypertensive, non-diabetic patients. Eur J Intern Med. 2010;21(5):414-417.
13. Giles TD, Khan BV, Lato J, Brener L, Ma Y, Lukic T. Nebivolol monotherapy in younger adults (younger than 55 years) with hypertension: a randomized, placebo-controlled trial. J Clin Hypertens. 2013;15(8):600-607.
14. Ladage D, Schwinger RH, Brixius K. Cardio-selective beta-blocker: pharmacological evidence and their influence on exercise capacity. Cardiovasc Ther. 2013;31(2):76-83.
15. Jacob S, Rett K, Wicklmayr M, Agrawal B, Augustin HJ, Dietze GJ. Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study. J Hypertens. 1996;14(4):489-494.
16. Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292(18):2227-2236.
17. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362(9377):7-13.
18. Aguilar D, Bozkurt B, Ramasubbu K, Deswal A. Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. J Am Coll Cardiol. 2009;54(5):422-428.
19. Haas SJ, Vos T, Gilbert RE, Krum H. Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials. Am Heart J. 2003;146(5):848-853.
20. Deedwania PC, Giles TD, Klibaner M, et al. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF. Am Heart J. 2005;149(1):159-167.
21. Kamp O, Sieswerda GT, Visser CA. Comparison of effects on systolic and diastolic left ventricular function of nebivolol versus atenolol in patients with uncomplicated essential hypertension. Am J Cardiol. 2003;92(3):344-348.
22. Nodari S, Metra M, Dei Cas L. Beta-blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long-term effects of atenolol vs. nebivolol. Eur J Heart Fail. 2003;5(5):621-627.
23. Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension: a randomized, controlled trial. Ann Intern Med. 1997;126(12):955-959.
24. Bell DS, Lukas MA, Holdbrook FK, Fowler MB. The effect of carvedilol on mortality risk in heart failure patients with diabetes: results of a meta-analysis. Curr Med Res Opin. 2006;22(2):287-296.
25. Contini M, Apostolo A, Cattadori G, et al. Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial. Int J Cardiol. 2013;168(3):2134-2140.
26. Ambrosio G, Flather MD, Bohm M, et al. Beta-blockade with nebivolol for prevention of acute ischaemic events in elderly patients with heart failure. Heart. 2011;97(3):209-214.
27. Van Bortel LM, Fici F,"; Palatini P. Efficacy and tolerability of nebivolol compared with other antihypertensive drugs: a meta-analysis. Am J Cardiovasc Drugs. 2008;8(1):35-44.
28. Wai B, Kearney LG, Hare DL, Ord M, Burrell LM, Srivastava PM. Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control. Cardiovasc Diabetol. 2012;11:14.
29. De Boer RA, Doehner W, van der Horst IC, et al. Influence of diabetes mellitus and hyperglycemia on prognosis in patients >=70 years old with heart failure and effects of nebivolol (data from the SENIORS trial). Am J Cardiol. 2010;106(1):78-86.
30. Tsujimoto T, Sugiyama T, Noda M, Kajio H. Intensive Glycemic Therapy in Patients With Type 2 Diabetes on Beta-Blockers. Diabetes Care. 2016;39(10):1818-1826.