Insulin resistance that exists in patients with essential hypertension and in those with non-insulin-dependent diabetes mellitus (NIDDM) may be the common denominator for the impaired glucose homeostasis and elevated blood pressure (BP) levels in patients with NIDDM. Therefore, treatment that improves insulin action may also improve BP levels. Consequently, a four-phase (glipizide v insulin) cross-over design study was conducted to determine a better effect of glipizide treatment on insulin sensitivity and the effect this has on BP in 19 NIDDM patients. Patients were subjected to 1 month of diet only (phase I) followed by 3 months of glipizide treatment (phase II), then an additional 1 month of diet only (phase III), and finally 3 months of insulin treatment (phase IV). At the end of phases I, II, and IV oral glucose tolerance tests (OGTT) were performed and plasma glucose, insulin, and C-peptide levels were analyzed. Fasting plasma glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides, glycated hemoglobin, fructosamine, and 2-h postprandial plasma glucose were also analyzed at each phase. Supine and sitting BP levels and body weights were determined biweekly during the study. With the exception of higher plasma insulin and C-peptide levels during the OGTT (area under the curve) in phase IV (insulin) v phase II (glipizide) (both P < .05), and higher fasting plasma insulin levels (P < .06), there were no consistently significant metabolic differences between phases IV and II.(ABSTRACT TRUNCATED AT 250 WORDS)