Metabolic and antihypertensive effects of moxonidine and moxonidine plus irbesartan in patients with type 2 diabetes mellitus and mild hypertension: a sequential, randomized, double-blind clinical trial.
BACKGROUND
The autonomic nervous system plays an important part in the homeostasis of blood pressure (BP), and sympathetic overactivity may contribute to metabolic conditions such as glycemic intolerance or insulin resistance.


OBJECTIVE
This study evaluated the anti-hypertensive and metabolic effects of moxonidine, a selective imidazoline II-receptor agonist that lowers BP by central inhibition of the sympathetic nervous system, and moxonidine plus the angiotensin II-receptor blocker irbesartan in patients with type 2 diabetes mellitus and mild hypertension.


METHODS
This was a study in patients with type 2 diabetes previously untreated with medication and untreated mild hypertension (diastolic blood pressure [DBP] >90 and <105 mm Hg). For the first 3 months of the study, all patients were treated for hypertension with moxonidine 0.2 mg once daily (M0.2) to establish a moxonidine baseline. After this single-arm period, patients were randomized to receive double-blind treatment with moxonidine 0.2 mg BID (M0.4) or moxonidine 0.2 mg plus irbesartan 150 mg (M0.2+1) once daily for 3 months. Changes in DBP, systolic blood pressure (SBP), body mass index (BMI), fasting and postprandial plasma glucose (FPG and PPG), fasting and postprandial plasma insulin (FPI and PPI), glycosylated hemoglobin (HbA(1c)), Homeostasis Model Assessment of insulin sensitivity (HOMA-S), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were evaluated at baseline, 3 months (end of single arm period), and 6 months (end of randomized treatment period).


RESULTS
The study enrolled 99 patients (50 men, 49 women; mean [SD] age, 55 [7] years; mean BMI, 26.8 [0.9]). No significant changes in BMI, PPG, PPI, TC, or LDL-C were observed over the entire study period. At 3 months, treatment with M0.2 was associated with significant improvements from baseline in SBP and DBP (P < 0.05), whereas there were no significant changes in HbA(1c), FPG, FPI, HOMA-S, HDL-C, or TG. At 6 months, significant decreases from baseline in HbA(1c), FPG, FPI, HOMA-S, and TG were observed in the M0.4 group (all, P < 0.05), but not in the M0.2+1 group. The M0.4 group also had a significant increase from baseline in HDL-C (P < 0.05) that was not seen in the M0.2+1 group. The changes in FPI and HOMA-S were significantly greater in the M0.4 group compared with the M0.2+1 group (P < 0.05). Significant decreases from baseline in SBP and DBP were observed in both the M0.4 and M0.2+1 groups (P < 0.02 and P < 0.01, respectively). No patient withdrew from the study because of a drug-related adverse event, and there were no clinically significant drug-related changes in laboratory values during the study.


CONCLUSIONS
In these patients with type 2 diabetes and mild hypertension, the M0.4 group had greater improvements in measures of glucose metabolism and the plasma lipid profile compared with those treated with M0.2+1.
Derosa
Giuseppe
G
Department o f Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. giuseppe.derosa@unipv.it
Cicero
Arrigo F G
AF
D'Angelo
Angela
A
Fogari
Elena
E
Salvadeo
Sibilla
S
Gravina
Alessia
A
Ferrari
Ilaria
I
Fassi
Raffaella
R
Fogari
Roberto
R
D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054755:Imidazoline Receptors; D000077405:Irbesartan; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011955:Receptors, Drug / Q000819:agonists; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D008055:Lipids; D011955:Receptors, Drug; D013777:Tetrazoles; C410887:imidazoline I1 receptors; C043482:moxonidine; D000077405:Irbesartan