Pyrazinoylguanidine Downregulates the Glucose Fatty-Acid Cycle in Hypertensive, Hyperinsulinemic Diabetic Patients
Eight hypertensive patients with noninsulin dependent diabetes mellitus (NIDDM) were administered the experimental drug pyrazinoylguanidine (PZG) either alone or in combination with calcium‐channel or β‐blockers. This treatment appeared to “downregulate” the glucose fatty acid cycle and reduced both...
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Veröffentlicht in: | Journal of clinical pharmacology 1994-12, Vol.34 (12), p.1234-1245 |
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Sprache: | eng |
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Zusammenfassung: | Eight hypertensive patients with noninsulin dependent diabetes mellitus (NIDDM) were administered the experimental drug pyrazinoylguanidine (PZG) either alone or in combination with calcium‐channel or β‐blockers. This treatment appeared to “downregulate” the glucose fatty acid cycle and reduced both systolic and diastolic blood pressures and mean body weight. Patients served as their own controls in this dose‐escalation study, which included placebo treatment (baseline) 3 weeks, 300 mg PZG for 3 weeks and 600 mg for 3 weeks. PZG reduced increased serum concentrations of free fatty acids (FFA), glucose, and triglycerides (TG). TG concentrations correlated inversely with serum HDL‐cholesterol concentrations. The beta‐blockers used by several patients increased their FFA, glucose, insulin and TG concentrations, as well as blunting their response to PZG. The calcium‐channel blockers exerted these effects to a much lesser extent. PZG reduced or abolished glycosuria, related to PZG's capacity to decrease hyperglycemia. Withdrawal of PZG restored glycosuria, as blood sugar increased. PZG was well tolerated. No patient reported any adverse effect or missed a weekly clinic visit (12 weeks). PZG deserves further study as supplementary and/or replacement therapy in NIDDM patients who are hypertensive and hyperlipidemic. |
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ISSN: | 0091-2700 1552-4604 |
DOI: | 10.1002/j.1552-4604.1994.tb04737.x |