Novel treatment approaches in hypertensive type 2 diabetic patients

Table 1 Studies which observed glucose reduction carvedilol

Ref.	Study design	Participants	Main results
Ehmer et al[30]	Prospective randomized open parallel group trial	49 non-insulin-dependent diabetics with mild to moderate HTN (carvedilol n = 25, metoprolol n = 24)	Blood glucose concentrations were maintained within narrow limits. Glycated haemoglobin A1 remained unchanged. There was a reduction in blood pressure in both groups
Giugliano et al[12]	Prospective single-blind randomized trial	45 patients with non-insulin-dependent DM and HTN (carvedilol n = 23, atenolol n = 22)	Patients treated with carvedilol had improved glucose and lipid metabolism and reduced lipid perioxidation compared to atenolol. Both reduced blood pressure
Bakris et al[11]	Prospective double-blind randomized trial	GEMINI study, 1235 patients with HTN and T2DM (carvedilol n = 498, metoprolol tartrate n = 737)	The mean glycosylated hemoglobin increased with metoprolol, but not with carvedilol. An improvement of insulin sensitivity was seen with carvedilol but not with metoprolol
Phillips et al[32]	Prospective double-blind randomized trial	GEMINI study 1235 patients with HTN and T2DM (carvedilol n = 498, metoprolol tartrate n = 737)	After and adjustment for age carvedilol was superior than metoprolol reducing baseline glycosylated hemoglobin and also in female patients. In black people carvedilol showed a reduction in IR greater than metoprolol
Kveiborg et al[40]	Prospective randomized open parallel group trial	19 patients with T2DM (metoprolol succinate n = 10, carvedilol n = 9) and 10 controls	Treatment with carvedilol did not change insulin-stimulated endothelial function, whereas it deteriorated with metoprolol
Torp-Pedersen et al[46]	Prospective double-blind randomized trial	3029 patients with chronic heart failure and T2DM (carvedilol n = 1511, metoprolol tartrate n = 1518)	Fewer patients treated with carvedilol developed T2DM than with metoprolol
Wai et al[47]	Observational cohort trial	125 patients with T2DM and heart failure (carvedilol n = 80, bisoprolol n = 45)	Carvedilol significantly improved glycemic control in subjects with heart failure and T2DM
Basat et al[48]	Prospective double-blind randomized trial	59 patients with ST-elevation myocardial infarction (carvedilol n = 26, metoprolol n = 31)	After myocardial infarction, carvedilol added to background therapy improved insulin resistance and lipid profile

T2DM: Type 2 diabetes mellitus; HTN: Hypertension.

Table 2 Studies which observed glucose reduction after renal denervation

Ref.	Study design	Participants	Main results
Mahfoud et al[14]	Prospective, controlled unblinded, randomized study	50 patients with resistant HTN (37 patients underwent catheter-based RDN and 13 patients in a control group	RDN improved glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure
Witkowski et al[65]	Prospective, nonrandomized, open-label study	10 patients with refractory hypertension and sleep apnea (7 men and 3 women, who underwent RDN)	RDN reduced blood pressure and improved glucose metabolism

HTN: Hypertension: RDN: Renal denervation.

Table 3 Comparison between carvedilol and renal denervation as therapeutic choices to reduce blood pressure and glucose levels in hypertensive type 2 diabetes mellitus patients

Therapeutic method	Mechanism of action	Medical indication	Mechanisms which explain glucose reduction	Contraindications	Side effects
Carvedilol	α1, non-selective β-blocker, antioxidant and calcium antagonist properties[17-20]	Treatment of hypertension[21] heart failure[25] and coronary artery disease[27]	An improvement in insulin sensitivity by a reduction in sympathetic nerve activity[74,75] and free radicals[68,69]	Bronchial asthma, second-third degree atrioventricular block, sick sinus syndrome, severe bradycardia, patients with severe cardiogenic shock and heart failure who use inotropic drugs and hepatic impairement[17-20]	Frequent: edema, dizziness, bradycardia, hypotension, nausea, diarrhea and blurred vision Rare: deterioration of renal and hepatic function[17-20]
RDN	Ablation of afferent and efferent renal nerves[51-55]	Treatment of resistant hypertension[56,57]	An improvement in insulin sensitivity by reduction in sympathetic nerve activity[56,57]	Polar or accessory arteries, renal artery stenosis, prior renal revascularization and glomerular filtration rate < 45 mL/min per 1.73 m2[56,57,62]	Renal artery dissection, postprocedural hypotension, femoral artery pseudoaneuryn, intraprocedural bradycardia[56,57]