For reaching near normal glycemic control, multiple daily insulin injections are necessary, although subcutaneous insulin therapy cannot get the physiological profile, results in hypoglycemia, weight gain, peripheral hyperinsulinemia, and may not be accepted for painful injections. Glucagon-like peptide 1(GLP-1) analogs and alternative routes of insulin, especially oral (enteric-gastrointestinal, inhaled) route, are most promising and attractive now. Biotechnology and biochemistry will make it possible to overcome several disadvantages of low absorption, short half-life, low bioavailablity, and many clinical trials are now in progress. We will show the review of these drugs and another candidate for the treatment of diabetic complications, protein kinase C inhibitor.