Clinical Characteristics of Japanese Type 2 Diabetic Patients Responsive to Sitagliptin

Abstract

Japanese type 2 diabetic patients were treated with sitagliptin to evaluate the efficacy of this agent, and also to investigate the clinical characteristics of those who responded to sitagliptin. In total, 1001 diabetic patients, inadequately controlled (HbA1c ≥ 6.5%) with oral hypoglycemic agents (OHA) other than DPP-4 inhibitors or with diet and exercise only, were enrolled. We added 50mg of sitagliptin to the therapeutic regimens of 410 patients including 68 OHA naïve patients, while the other 591 patients were switched from a single OHA to 50 mg of sitagliptin. After 6 months, glycemic control was significantly improved due to both reduced insulin resistance, as demonstrated by a significant HOMA-R reduction, and recovery of pancreatic β cell function, as assessed by HOMA-β and the proinsulin/insulin (PI/I) ratio. In the bivariable analysis, a good response, defined as an HbA1c reduction during the 6 months of at least 0.9%, was associated with high HbA1c and PI/I at baseline and combination treatments with sulfonylurea, biguanide and α-glucosidase inhibitors, but not with obesity. On the other hand, in the multivariable regression analysis, only high baseline HbA1c and combination treatment with an α-glucosidase inhibitor were significantly associated with a good response to sitagliptin. In patients with type 2 diabetes, the addition of sitagliptin or switching from another OHA to this agent achieved an HbA1c reduction without overloading β cells. In particular, we suggest that a good response to sitagliptin can be expected when this agent is combined with an α-glucosidase inhibitor (UMIN No. #000014157).

Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy inJapanese people with type 2 diabetes

“…This trial was conducted to meet the “Guideline for Clinical Evaluation of Oral Hypoglycaemic Agents” issued by the Japanese Ministry of Health, Labour and Welfare, which advises that new drugs are assessed as monotherapy to investigate their isolated effects. A specific comparator is not stipulated in the guideline; however, sitagliptin was chosen as an active comparator because it is widely available in Japan, and has a well‐known efficacy and safety profile. The trial was conducted in compliance with the International Conference on Harmonisation Good Clinical Practice guidelines and the Declaration of Helsinki .…”

“…Sitagliptin, a once‐daily dipeptidyl peptidase‐4 (DPP‐4) inhibitor, is a widely used oral antidiabetic drug (OAD), and the most commonly used DPP‐4 inhibitor in Japan . DPP‐4 inhibitors achieve glycaemic control by inhibiting DPP‐4‐dependent inactivation of both GLP‐1 and gastric inhibitory polypeptide (GIP), thereby enhancing GLP‐1 and GIP receptor signalling, and thus are distinct from GLP‐1 RAs, which stably activate GLP‐1 receptor signalling …”

“…6,7 Sitagliptin, a once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor, is a widely used oral antidiabetic drug (OAD), and the most commonly used DPP-4 inhibitor in Japan. 8 which stably activate GLP-1 receptor signalling. 9 Semaglutide has been evaluated in the "Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes" (SUSTAIN) programme, consisting of six phase III global clinical trials that evaluated the efficacy and safety (including cardiovascular outcomes) of semaglutide vs a range of comparators, including sitagliptin.…”