Can people with diabetes take beta blockers?

Blood Pressure Control in Diabetic Patients

Intensive blood pressure control is important for people with diabetes. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the American Diabetes Association recommend blood pressure in diabetics to be controlled to 130/80 mm Hg or lower.¹ Most diabetic patients require treatment with two or more drugs to control blood pressure, and clinical studies on various antihypertensive medications show benefits in both type 1 and type 2 diabetic patients with hypertension. The United Kingdom Prospective Diabetes Study (n=5,102) found that each 10 mm Hg decrease in systolic blood pressure was associated with 15% reduction in the rate of diabetes-related mortality, 11% in myocardial infarction, and 13% in microvascular complications of retinopathy or nephropathy.² The large Hypertension Optimal Treatment trial (n=18,790) found that compared to diabetic patients randomized to a target diastolic blood pressure of ≤90 mm Hg, those assigned to a target of ≤80 mm Hg showed a 51% reduction in major cardiovascular events (relative risk [RR] 2.06, 95% confidence interval [CI] [1.24 – 3.44], p=0.005).³

Nonvasodilating vs. Vasodilating Beta blockers

Previously, the use of beta blockers was discouraged for diabetic patients, because beta blockers were thought to worsen insulin resistance⁴ and deteriorate lipoprotein metabolism.⁵ Manufacturers continue to suggest that patients with diabetes mellitus should use beta blockers with caution.^6-10 They warn that beta blockers can mask symptoms of hypoglycemia and further enhance lowering of blood sugar levels if taken with insulin or oral hypoglycemic medications.^6-10 However, these issues are often easily managed and are not absolute contraindications.¹

Antihypertensive benefits of beta blockers as a monotherapy are unclear for diabetics. However, vasodilating beta blockers have neutral or beneficial effects on glucose metabolism and may be safe to use by patients with diabetes mellitus and hypertension.¹¹ Recent studies recommend encouraging the use of vasodilating beta blockers in diabetic patients because of the overwhelming benefits of controlling blood pressure.¹²

There are three groups of beta blockers: non-selective, beta-1-selective, and beta-1-alpha-selective. Each is different in how they affect the three adrenergic receptors (beta-1, beta-2, and alpha).¹³ Because of their differing mechanisms of action, they have differing effects on blood sugar levels.¹¹ Nonvasodilating beta blockers include the non-selective type, such as propranolol and penbutolol, and the beta-1-selective type, such as atenolol and metoprolol. These types of beta blockers may worsen glycemic control and raise blood glucose levels. However, vasodilating (alpha-beta-selective) beta blockers, such as carvedilol, nebivolol, do not raise blood glucose levels and may have neutral or beneficial effects on glucose metabolism.

Clinical Trials

Many studies tested the use of various beta blockers on diabetic patients with hypertension and found that vasodilating beta blockers may be safe to use in diabetic patients.^14-17 Studies use HbA1c blood levels as a measure of average blood sugar levels¹⁸ over the previous three months.¹⁹ Results of this test can also be used to diagnose diabetes if HbA1c levels are higher than 6.5%.

Studies show that vasodilating beta blockers, such as carvedilol and nebivolol, improve metabolic profiles compared to nonvasodilating beta blockers such as metoprolol.^14,15 One study randomized 1,235 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension to either metoprolol or to carvedilol, each twice a day.¹⁴ In the group taking metoprolol, the mean HbA1c level increased significantly from baseline to five months of maintenance therapy (0.15%, 95% [CI] [0.08 – 0.22], p<0.001). Unlike metoprolol, carvedilol had no effect on the mean change in HbA1c level from baseline (0.02%, 95% [CI] [-0.06 – 0.10], p=0.65). Carvedilol treatment showed significant improvements in insulin resistance when compared to baseline (-9.1%, p=0.004), and also when compared to the metoprolol treatment (-7.2%, 95% [CI] [-13.8 – -0.2], p=0.004). Insulin resistance is measured and reported with a clinical index called Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), derived from fasting insulin (μU/mL) and glucose levels (mg/dL).^14,20 Asymptomatic and symptomatic hypoglycemic episodes occurred in similar rates in carvedilol and metoprolol groups. Three participants (0.4%) withdrew from study due to hypoglycemia on metoprolol.

Another study randomized 72 hypertensive patients to either metoprolol or nebivolol treatment.¹⁵ The metoprolol group showed significant increases in glucose level (from 95.14 ± 11.38 mg/dL to 97.17 ± 7.83 mg/dL, p<0.36) and insulin resistance (2.67 ± 1.07 to 2.83 ± 0.42, p=0.39), when compared to baseline. The nebivolol group showed no significant changes in the glucose level compared to the baseline, but showed significant reduction in insulin resistance (2.79 ± 1.16 to 2.29 ± 1.24, p=0.008). Differences in glucose level (p=0.12) and insulin resistance (p=0.003) between the metoprolol and nebivolol groups were significant.

Carvedilol and nebivolol improved glucose metabolism and decreased blood glucose levels, when compared to atenolol, a nonvasodilating beta blocker.^16,17 A randomized, double-blinded trial of 45 patients found that carvedilol treatment of patients with NIDDM and hypertension improved glucose and lipid metabolism.¹⁶ Compared to atenolol, carvedilol treatment decreased fasting plasma glucose levels by 0.3 ± 0.5 mmol/L (p=0.01) and insulin levels by 8.0 ± 8.0 pmol/L (p<0.001). When compared to baseline, the HbA1c level was decreased by 1.4% in the carvedilol group, whereas it increased by 4% in the atenolol group (p<0.001). Insulin sensitivity index increased during carvedilol treatment but decreased during atenolol treatment (p≤0.01). The study concluded that carvedilol may offer advantages to patients with diabetes. Neither drug prolonged hypoglycemia and glucose recovery. A different trial on 30 hypertensive hyperlipidemic patients compared the effect of nebivolol to atenolol on metabolic profile.¹⁷ The study found that both nebivolol and atenolol administration did not change blood glucose levels. However, nebivolol decreased insulin resistance by 20% (34 ± 16 at baseline to 27 ± 13.6, p=0.05), whereas atenolol had no effect.

^References

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