Kawazu Shoji, Kanazawa Yasunori, Iwamoto Yasuhiko, Katayama Shigehiro, Origasa Hideki, Kuzuya Takeshi
1The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6 Nihonbashi, Bakuro-cho, Chuo-ku, Tokyo, 103-0002 Japan.
2Jichi Medical University, Tochigi, Japan.
Diabetol Int. 2017 Apr 18;8(4):350-365. doi: 10.1007/s13340-017-0319-x. eCollection 2017 Nov.
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-naïve 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 ( = 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 ( < 0.05 and < 0.01 respectively). Significant reductions of ΔBMI were seen similarly in both groups throughout the study ( < 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 ( < 0.05 or < 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 ( < 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".
为有效预防2型糖尿病患者高血糖恶化，除了终身坚持并非易事的生活方式干预外，早期引入药物治疗的临床疗效值得关注。这是一项随机非盲对照临床研究，旨在观察初治2型糖尿病患者早期仅进行生活方式干预以及联合单一药物治疗对轻度高血糖的抑制作用，这些患者的空腹血糖（FPG）和糖化血红蛋白（HbA1c）分别低于140mg/dl和7.4%。对照组（N组）接受常规设施辅助的传统生活方式干预，而药物干预组（D组，由4个亚组组成）额外接受四种口服降糖药之一的单一药物治疗，即磺脲类（SU）、α-葡萄糖苷酶抑制剂、双胍类和二肽基肽酶-4抑制剂。参与者计划随访3年，以将血糖控制维持在主要终点以下，主要终点定义为即使D组必要时增加口服药物剂量，FPG≥140mg/dl和HbA1c≥7.4%同时首次出现。通过Kaplan-Meyer曲线分析，3年内N组与由4个亚组组成的D组之间主要终点的发生率无差异（P = 0.405）。另一方面，3年内D组的ΔFPG（Δ：相对于基线的增量变化）和ΔHbA1c与N组相比显著降低（分别为P<0.05和P<0.01）。在整个研究过程中，两组的ΔBMI均显著降低（P<0.05），但两组之间无差异。在这5个亚组中，与N组相比，D组的三个单一药物治疗亚组在3年内ΔHbA1c显著降低（P<0.05或P<0.01），除了SU亚组，该亚组在研究后半期ΔBMI和ΔHbA1c有升高趋势。所有参与者中，目标HbA1c低于7.4%、7.0%和6.5%的最终达标率在D组中往往高于N组（7.4%时P<0.047，但其他情况无统计学意义）。总之，除使用SU药物外，在生活方式干预基础上早期引入药物单一治疗似乎可在3年内用小剂量降糖药抑制轻度高血糖。尽管需要更大规模的试验才能得出结论，但早期采用合适的单一治疗可能有效实现并维持“安全血糖水平”。
