LEO P. KRALL, M.D.; ROBERT F. BRADLEY, M.D.
The search for orally effective hypoglycemic agents preceded the advent of insulin by several years. Although this report evaluates the biguanides and compares them to other hypoglycemic agents, a look at the compounds in earlier use, particularly the guanidines, shows that the roots of the problem go back over 40 years.
Early observation that tetany resulting from parathyroidectomy was accompanied by hypoglycemia1 and increased levels of guanidine in the blood2 led in 1918 to Watanabe's3 correlation between a marked effect of guanidine on intermediary metabolism and decreased blood glucose levels. Frank, Stern and Nothmann4 showed that
KRALL LP, BRADLEY RF. CLINICAL EVALUATION OF FORMAMIDINYLIMINOUREA, A NEW BIGUANIDE ORAL BLOOD SUGAR LOWERING COMPOUND: COMPARISON WITH OTHER HYPOGLYCEMIC AGENTS1. Ann Intern Med. ;50:586–613. doi: 10.7326/0003-4819-50-3-586
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Published: Ann Intern Med. 1959;50(3):586-613.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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