Objective To investigate the changes of blood glucose, HbA1c, and incidence of hypoglycemia in the very old patients (over 80 years) with type 2 diabetes mellitus (T2DM) after the treatment of lantus with glucobay or Novomix 30, and the clinical significance. Methods A total of 120 very old T2DM patients poorly controlled with oral hypoglycemic drugs admitted in our department from July 2011 to June 2012 were subjected in this study. They were randomly divided into lantus with glucobay group and Novomix 30 group (n＝60 in each group). Lantus was injected before breakfast, and glucobay was taken with meals, while Novomix 30 was injected before morning and evening meals for total 16 weeks. Fasting blood glucose (FBG) and 2-hour postprandial blood glucose (2hPBG), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), the decrease of HbA1c, and the incidence of hypoglycemia were compared between the two groups. Results After the treatment, blood glucose, TG, TC, LDL-C and HbA1c were decreased in the two groups though without significant difference (P＞0.05). HbA1c was decreased from (8.8%±2.0%) to (7.1%±1.2%) in the glucobay group, and from (8.9%±2.4%) to (7.0%±1.2%) in Novomix 30 group, with no significant difference between them (P＞0.05). The incidence of hypoglycemia was significantly lower in glucobay group than in Novomix 30 group (3.3% vs 13.3%, P＜0.01). Conclusion Lantus combined with glucobay and Novomix 30 have the similar improvement in FBG, 2hPBG, TG, TC, LDL-C and HbA1c. But the combination with glucobay has significantly lower incidence of hypoglycemia.