Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/physiopathology , Heart/physiopathology , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Blood Flow Velocity/physiology , Blood Pressure/physiology , Blood Volume/physiology , Coronary Circulation/physiology , Coronary Disease/physiopathology , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Male , Metformin/therapeutic use , Middle Aged , Pilot ProjectsABSTRACT
The pharmacological arsenal available today for the treatment of type II diabetes is often insufficient to allow optimal control of the disease. Each agent corrects only one or a few of the multiple defects that characterise type II diabetes. Currently, new drugs are under development that target several of the clinical abnormalities. These agents include the gastrointestinal peptides, glucagon-like polypeptide-1 (GLP-1) and amylin, and their analogues. New rapid- and long-acting insulin analogues will also constitute interesting treatment alternatives.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Gastrointestinal Hormones/therapeutic use , Hypoglycemic Agents/therapeutic use , Peptides/therapeutic use , HumansABSTRACT
OBJECTIVE: To compare the long-term effects of the angiotensin-converting enzyme (ACE)-inhibitor quinapril and the cardioselective beta-adrenergic blocking agent metoprolol on glycaemic control, with glycosylated haemoglobin (HbA1c) as the principal variable, in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. DESIGN: A randomized, double-blind, double-dummy, multicentre study during 6 months preceded by a 4 week wash-out and a 3 week run-in placebo period. Quinapril (20 mg) and metoprolol (100 mg, conventional tablets) were given once daily. No change was made in the treatment of diabetes (diet and hypoglycaemic agents). SUBJECTS: Seventy-two patients fulfilling the criteria were randomized and entered the double-blind period. Twelve patients did not complete the study. Sixty patients, 26 on quinapril and 34 on metoprolol, were available for the final analysis. MAIN OUTCOME MEASURES: The effect was assessed by changes in HbA1c, the fasting serum glucose and the post-load serum glucose, C-peptide and insulin levels during the oral glucose tolerance test. RESULTS: In the quinapril group, the fasting serum glucose, oral glucose tolerance and the C-peptide and insulin responses, determined as the incremental area under the curves (AUC), showed no change, but the mean HbA1c level increased from 6.2 +/- 1.1% to 6.5 +/- 1.3% (P < 0.05). In the metoprolol group, the rise in the mean level of HbA1c, from 6.3 +/- 1.0% to 6.8 +/- 1.3% (P < 0.01), tended to be more marked than after quinapril, although there was no significant difference between the increments. The mean fasting serum glucose showed an increase from 9.1 +/- 1.9 mM to 10.1 +/- 2.8 mM (P < 0.01) which correlated significantly with the duration of diabetes (P < 0.01) and the increase in fasting serum triglycerides (P < 0.001). Moreover, in the metoprolol group we found significant decreases in the oral glucose tolerance as well as C-peptide and insulin responses to the glucose load. CONCLUSIONS: Treatment with quinapril for 6 months appears to have advantages over metoprolol in NIDDM patients with hypertension. Although treatment with quinapril or metoprolol over 6 months was concomitant with a rise in the HbA1c, increased fasting blood glucose, decreased oral glucose tolerance and decreased C-peptide and insulin responses to a glucose challenge were observed only in patients treated with metoprolol.