Combination of disease duration‐to‐age at diagnosis and hemoglobin A1c‐to‐serum C‐peptide reactivity ratios predicts patient response to glucose‐lowering medication in type 2 diabetes: A retrospective cohort study across Japan (JDDM59)

Abstract

Aims/Introduction Knowing the collective clinical factors that determine patient response to glucose‐lowering medication would be beneficial in the treatment of type 2 diabetes. We carried out a retrospective cohort study to explore the combination of clinical factors involved in its therapeutic efficacy. Materials and Methods The results of cohort studies retrieved using the CoDiC® database across Japan from January 2005 to July 2018 were analyzed based on criterion that using insulin therapy indicates severe type 2 diabetes. Results A logistic regression analysis showed that age at diagnosis, disease duration, hemoglobin A1c (HbA1c) and serum C‐peptide reactivity (CPR) at medication commencement were associated with the probability of insulin treatment. Receiver operating characteristic curve showed that these clinical factors predicted insulin treatment positivity with an area under the curve of >0.600. The area under the curve increased to 0.674 and 0.720 for the disease duration‐to‐age at diagnosis ratio and HbA1c‐to‐CPR ratio, respectively. Furthermore, area under the curve increased to 0.727 and 0.750 in the indices (duration‐to‐age ratio at diagnosis × 43 + HbA1c) and (duration‐to‐age ration at diagnosis × 21 + HbA1c‐to‐CPR ratio), respectively. After stratification to three groups according to the indices, monthly HbA1c levels during 6 months of treatment were higher in the upper one‐third than in the lower one‐third of patients, and many patients did not achieve the target HbA1c level (53 mmol/mol) in the upper one‐third, although greater than fourfold more patients were administered insulin in the upper one‐third. Conclusions The combination of disease duration‐to‐age at diagnosis and HbA1c‐to‐CPR ratios is a collective risk factor that predicts response to the medications.

Efficacy and safety of imeglimin add‐on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double‐blind, placebo‐controlled phase 3 trial with a 36‐week open‐label extension period

“…The addition of imeglimin to insulin therapy in patients with poor glycaemic control could therefore provide benefits to elderly patients who are known to have functional limitations (eg, difficulty in accurately injecting insulin), comorbidities or insufficient social support. 5,36 Some limitations need to be addressed regarding the present study. First, our results may not be generalizable to patients in other countries or to White populations.…”

“…However, the efficacy profile, defined by a significant HbA1c decrease, was consistent across subgroup analyses, suggesting that imeglimin is a new and safe treatment option in the elderly population. The addition of imeglimin to insulin therapy in patients with poor glycaemic control could therefore provide benefits to elderly patients who are known to have functional limitations (eg, difficulty in accurately injecting insulin), comorbidities or insufficient social support 5,36 …”

“…In Japan, where approximately 7.6% of people aged 20 to 79 years have the disease, 3 the consensus‐based guidelines provided by the Japan Diabetes Society recommend that patients with type 2 diabetes mellitus initiate treatment with an oral hypoglycaemic agent or an injectable agent when lifestyle and diet modifications are inadequate to maintain glycaemic control 4 and emphasize the importance of individualized, patient‐centred care. In this context, the use of insulin has become quite prevalent, with potentially more than 10% of type 2 diabetes patients receiving insulin either as a monotherapy or in combination with other oral antidiabetes drugs 5 . Importantly, insulin use in Japanese patients with type 2 diabetes is more frequent among older individuals, in those diagnosed at an earlier age, and with longer disease duration 5 .…”

“…5 Importantly, insulin use in Japanese patients with type 2 diabetes is more frequent among older individuals, in those diagnosed at an earlier age, and with longer disease duration. 5 Although combination therapies improve glycaemic control, they may increase the risk of side effects, particularly in the elderly population and in patients with diabetes complications, who are often burdened with additional therapies for treatment of comorbidities. Consequently, new alternative antidiabetic medicines that can be used in combination with insulin to achieve sustained efficacy and a good safety/tolerability profile are still needed as treatment options.…”

“…In this context, the use of insulin has become quite prevalent, with potentially more than 10% of type 2 diabetes patients receiving insulin either as a monotherapy or in combination with other oral antidiabetes drugs 5 . Importantly, insulin use in Japanese patients with type 2 diabetes is more frequent among older individuals, in those diagnosed at an earlier age, and with longer disease duration 5 . Although combination therapies improve glycaemic control, they may increase the risk of side effects, particularly in the elderly population and in patients with diabetes complications, who are often burdened with additional therapies for treatment of comorbidities.…”