Effect of antihyperglycemic drug monotherapy to prevent the progression of mild hyperglycemia in early type 2 diabetic patients: the Japan Early Diabetes Intervention Study (JEDIS)

To effectively prevent the worsening of hyperglycemia in type 2 diabetes mellitus, it is of interest to see the clinical efficacy of early introduction of pharmacotherapy in addition to lifestyle intervention which is not always easy to continue throughout life. This is a randomized unblinded comparative clinical study on suppressive effects of lifestyle intervention alone and additional monotherapies for mild hyperglycemia at an early stage of treatment-naive type 2 diabetic patients, whose fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) are less than 140 mg/dl and 7.4%, respectively. The control group (group N = arm N) received conventional lifestyle intervention assisted by routine facilities, while the pharmacological intervention group (group D composed of 4 arms) was additionally treated by monotherapy with one of four kinds of oral antihyperglycemic agents i.e., sulfonylurea (SU), α-glucosidase inhibitor, biguanide and dipeptidyl peptidase-4 inhibitor. The participants were scheduled to follow up for 3 years to maintain glycemic control below primary endpoint which was defined as the first occurrence of FPG ≥140 mg/dl and HbA1c ≥7.4% simultaneously even by increasing doses of oral drug in group D, if necessary. The outcomes of occurrences of primary endpoint were not different between group N and group D composed of 4 arms during 3 years by Kaplan–Meyer plots (p = 0.405). On the other hand, ΔFPG (Δ: incremental change from baseline) and ΔHbA1c in group D significantly decreased when compared to those of group N during 3 years (p < 0.05 and p < 0.01 respectively). Significant reductions of ΔBMI were seen similarly in both groups throughout the study (p < 0.05), but did not differ between two groups. Among these 5 arms, significant decreases of ΔHbA1c were observed in three monotherapy arms of group D compared to arm N for 3 years (p < 0.05 or p < 0.01), except for arm SU in which ΔBMI and ΔHbA1c tended to increase at the latter half of the study. The final achievement rates of target HbA1c less than 7.4, 7.0 and 6.5% in all the participants tended to be higher in group D than in group N (p < 0.047 for 7.4%, but not significant for others). In conclusion, the early introduction of pharmacological monotherapy in addition to lifestyle intervention seem to suppress mild hyperglycemia with small doses of antihyperglycemic agents for 3 years, except for the use of SU drug. Although a larger scale of trial will be necessary to conclude, the early treatment with suitable monotherapy could be effective to bring and keep “safe level of glycemia”.