Essential and unnecessary medicines for diabetes

Abstract

Diabetes is a disease with insufficient effects of insulin which acts on more than 100 kinds of genes and essential for metabolism of nutrients including carbohydrates, protein and lipids and for normal function of each cell in the body. Generally believed endpoint“control blood glucose level normal”is misleading. True endpoint is to live long by relieving the deficiency of insulin effects for nutrients to be appropriately utilized to maintain normal function of the body and to reduce complications. The outcome of clinical trials must be all-cause mortality because cause-specific mortality or incidence of diseases may miss the adverse effects especially on cancer incidence leading to shortening of overall survival. Insulin but not insulin analog is the only recommended medicine for diabetes tobe used if appropriate energy of carbohydrate restriction diet, moderate exercise and sufficient sleep without sleeping pills were ineffective. Sulfonyl urea（SU）increases insulin secretion by closing K ATP channels in pancreatic β cells but induces secondary failure without proof of prolongation oflife. Biguanide is an inhibitor of mitochondrial chain complex I（a mitochondrialpoison）and open K ATPchannels leading to reduction of insulin secretion（oppositeto SU）and recover the sensitivity to insulin. It may be beneficial for only thosewith 30 or more of BMI. The incretin-related agents（DPP-4 inhibitor and GLP-1 analogue）show carcinogenicity in both animal toxicity studies and clinical trials. The long term prognosis of incretin-related agents and SGLT-2 inhibitors are not proved because of the serious methodological failures.y